Clopidogrel resistance is common in patients undergoing vascular and coronary interventions.

OBJECTIVES: "Clopidogrel resistance," also defined as heightened platelet reactivity (HPR) while on clopidogrel therapy, may lead to a sub-optimal antiplatelet effect and a potential thrombotic event. There is limited literature addressing the prevalence of HPR in a large cohort of patients receiving either coronary or endovascular interventions. METHODS: In a large integrated healthcare system, patients with a P2Y12 reaction units (PRU) test were identified. HPR was defined as a PRU ≥ 200 during clopidogrel therapy. Vascular and coronary interventions were identified utilizing CPT codes, HPR prevalence was calculated, and Fischer's exact test was used to determine significance. RESULTS: From an initial cohort of 2,405,957 patients (October 2014 to January 2020), we identified 3301 patients with PRU tests administered. Of these, 1789 tests had a PRU ≥ 200 (HPR overall prevalence, 54%). We then identified 1195 patients who underwent either an endovascular or coronary procedure and had a PRU measurement. This corresponded to 935 coronary and 260 endovascular interventions. In the coronary cohort, the HPR prevalence was 54% (503/935). In the vascular cohort, the HPR prevalence was 53% (137/260); there was no difference between cohorts in HPR prevalence (p = 0.78). CONCLUSION: "Clopidogrel resistance" or HPR was found to be present in nearly half of patients with cardiovascular disease undergoing intervention. Our data suggest HPR is more common in the cardiovascular patient population than previously appreciated. Evaluating patients for HPR is both inexpensive ($25) and rapid (< 10 min). Future randomized studies are warranted to determine whether HPR has a clinically detectable effect on revascularization outcomes.

Epidemiology, evaluation, and management of conduction disturbances after transcatheter aortic valve replacement.

Aortic stenosis is the most common valvulopathy requiring replacement by means of the surgical or transcatheter approach. Transcatheter aortic valve replacement (TAVR) has quickly become a viable and often preferred treatment strategy compared to surgical aortic valve replacement. However, transcatheter heart valve system deployment not infrequently injures the specialized electrical system of the heart, leading to new conduction disorders including high-grade atrioventricular block and complete heart block (CHB) necessitating permanent pacemaker implantation (PPI), which may lead to deleterious effects on cardiac function and patient outcomes. Additional conduction disturbances (e.g., new-onset persistent left bundle branch block, PR/QRS prolongation, and transient CHB) currently lack clearly defined management algorithms leading to variable strategies among institutions. This article outlines the current understanding of the pathophysiology, patient and procedural risk factors, means for further risk stratification and monitoring of patients without a clear indication for PPI, our institutional approach, and future directions in the management and evaluation of post-TAVR conduction disturbances.

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis.

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis: An Expert Statement.

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

Acute stroke intervention.

Ischemic strokes will make up most (>80%) of the three-quarters of a million strokes that will occur in Americans this year. Reperfusion therapy is the fundamental strategy for the treatment of acute ischemic stroke. Reperfusion therapy may be accomplished noninvasively (intravenous thrombolysis) or invasively with catheter-based treatments (intra-arterial thrombolysis, thrombectomy, or angioplasty). Currently, a large majority of patients with acute ischemic stroke do not receive any form of reperfusion therapy owing to their delayed presentation (>3 hours) and lack of skilled man power for on-demand endovascular treatment. Paradoxically, improved success rates for reperfusion have been reported with the newer thrombectomy catheters, called "stentreivers." An option for broadening access for patients who need endovascular therapy would be to use interventional cardiologists with carotid stent experience who can help to provide 24 × 7 × 365 coverage.

Carotid artery stenting: patient, lesion, and procedural characteristics that increase procedural complications.

From the earliest experiences with carotid artery stenting (CAS) presumptive high risk features have included thrombus-containing lesions, heavily calcified lesions, very tortuous vessels, and near occlusions. In addition patients have been routinely excluded from CAS trials if they have contra-indications to dual antiplatelet therapy (aspirin and thienopyridines), a history of bleeding complications and severe peripheral arterial disease (PAD) making femoral artery vascular access difficult. Variables that increase the risk of CAS complications can be attributed to patient characteristics, anatomic or lesion features, and procedural factors. Clinical features such as older age (≥80 years), decreased cerebral reserve (dementia, multiple prior strokes, or intracranial microangiopathy) and angiographic characteristics such as excessive tortuosity (more than two 90° bends within 5 cm of the target lesion) and heavy calcification (concentric calcification ≥ 3 mm in width) have been associated with increased CAS complications. Other high risk CAS features include those that prolong catheter or guide wire manipulation in the aortic arch, make crossing a carotid stenosis more difficult, decrease the likelihood of successful deployment or retrieval of an embolic protection device (EPD), or make stent delivery or placement more difficult. Procedure volume for the operator and the catheterization laboratory team are critical elements in reducing the risk of the procedure. In this article, we help CAS operators better understand procedure risk to allow more intelligent case selection, further improving the outcomes of this emerging procedure.

A randomized trial of intravenous n-acetylcysteine to prevent contrast induced nephropathy in acute coronary syndromes.

BACKGROUND: Pharmacokinetic data suggests that the intravenous form of n-acetylcysteine (NAC) may be more effective than the oral formulation in preventing contrast induced nephropathy (CIN). NAC owing to its anti-oxidant properties might be beneficial for patients with acute coronary syndromes (ACS) who are at increased risk for CIN. The aim of this prospective randomized, single-center, double-blind, placebo controlled trial (NCT00939913) was to assess the effect of high-dose intravenous NAC on CIN in ACS patients undergoing coronary angiography and/or percutaneous coronary intervention (PCI). METHODS: We randomized 398 ACS patients scheduled for diagnostic angiography ± PCI to an intravenous regimen of high-dose NAC (1,200 mg bolus followed by 200 mg/hr for 24 hr; n = 206) or placebo (n = 192). The primary end-point was incidence of CIN defined as an increase in serum creatinine concentration ≥ 25% above the baseline level within 72 hr of the administration of intravenous contrast. RESULTS: There was no difference found for the primary end point with CIN in 16% of the NAC group and in 13% of the placebo group (p = 0.40). Change in serum cystatin-C, a sensitive marker for renal function, was 0.046 ± 0.204 in the NAC group and 0.002 ± 0.260 in the control group (p = 0.07). CONCLUSION: In ACS patients undergoing angiography ± PCI, high-dose intravenous NAC failed to reduce the incidence of CIN.

A simple percutaneous technique for hemostasis and closure after transcatheter aortic valve implantation.

Access closure is a key element to successful retrograde percutaneous transfemoral transcatheter aortic valve implantation. It requires large-bore femoral arterial access (18Fr-28Fr) which most operators manage with surgical access and closure under general anesthesia. We report a case example of how, using our center's peripheral interventional experience, we have developed a simple five step technique to achieve hemostasis percutaneously.

Elective percutaneous intervention for intracranial atherosclerotic stenoses by interventional cardiologists.

BACKGROUND: Current "best" medical therapy with anti-platelet and/or anti-thrombotic agents for symptomatic atherosclerotic intracranial (IC) disease is associated with high recurrence. IC catheter-based therapy (CBT) using balloon angioplasty with or without stent placement is an option for patients who have failed medical therapy. We sought to examine the outcomes of CBT for patients with symptomatic IC arterial disease managed by experienced interventional cardiologists. METHODS: We retrospectively studied 89 consecutive symptomatic patients with 99 significant (≥70% diameter) IC arterial stenoses who underwent CBT. CBT was performed by experienced interventional cardiologists with the consultative support of a neurovascular team. The primary endpoint was stroke and vascular death. RESULTS: Procedure success was achieved in 96/99 (97%) lesions and percent diameter stenosis was reduced from 91% ± 7.5% preprocedure to 19% ± 15% postprocedure (P < 0.001). The rate of in-hospital periprocedural stroke and all death was 3%. The primary endpoint of stroke and vascular death rate at 1 year was 5.7% (5/88) and at 2 years was 13.5% (11/81). The 2-year all-cause mortality was 11.3% (10/88). CONCLUSIONS: For patients with symptomatic IC arterial stenosis who have failed medical therapy or are considered very high risk for stroke, CBT performed by experienced interventional cardiologists is safe and offers both high procedural success rates and excellent clinical outcomes at 1 year. CBT is an attractive option for this high-risk patient population considering the expected 12-15% rate of recurrent stroke at 1 year.

Factors related to a clinically silent peri-procedural drop in hemoglobin with coronary and peripheral vascular interventions.

Clinically evident and subclinical peri-procedural bleeding following interventional therapies are associated with adverse cardiovascular outcomes. The risk factors for clinically evident bleeding have been well described. Despite the well-documented association of adverse outcomes for patients with a subclinical peri-procedural hemoglobin drop, the clinical predictors have not yet been defined. We identified 1176 consecutive patients with a subclinical drop in hemoglobin (fall of ≥ 1 g/dl in patients without clinical bleeding) following percutaneous coronary interventions (PCI) and peripheral vascular interventions (PVI). Multivariate logistic regression analysis was performed. A subclinical peri-procedural hemoglobin drop ≥ 1 g/dl was identified in 41% (400/972) of PCI and in 49% (213/435) of PVI. More than one access site predicted a higher risk of a subclinical drop in hemoglobin in both groups. A body mass index ≥ 30 predicted a lower risk of a subclinical drop in hemoglobin in both groups. For PCI, creatinine clearance < 60 ml/min was associated with a higher risk of a subclinical drop in hemoglobin. In conclusion, clinically silent peri-procedural hemoglobin fall ≥ 1 g/dl is common in patients undergoing both coronary and peripheral percutaneous intervention. Predictors identified in our study will need prospective validation.

Catheter-based therapy of common femoral artery atherosclerotic disease.

The objective of this paper is to describe outcomes of endovascular therapy in patients with symptomatic common femoral artery (CFA) lesions. Symptomatic atherosclerotic disease of the common femoral artery is an uncommon clinical entity, and there is no consensus regarding the suitability of catheter-based therapy. We reviewed the records of 26 consecutive patients treated with catheter-based therapy for symptomatic CFA lesions between 1994 and 2009. Angiographic success and procedure success were obtained in all vessels and in all patients. At 1 year, 100% (16/16) of the claudication patients and 70% (7/10) of the critical limb ischemia (CLI) patients maintained clinical success. The ankle- brachial index (ABI) significantly improved from a baseline of 0.47 ± 0.18 to 0.77 ± 0.18 (p < 0.001) after the procedure. At their most recent clinic visit (31 months ± 14 months), clinical success was maintained in 100% of the claudication patients and in 70% (7/10) of the CLI patients. During the follow-up period, femoral vascular access for an unrelated procedure was obtained through the CFA stent. In conclusion, patients with symptomatic CFA atherosclerotic disease obtained excellent clinical outcomes with angioplasty with stenting. We found that angioplasty with stenting of the CFA did not preclude future CFA vascular access. Our data suggest that catheter-based therapies should be considered as an option to open surgery in selected patients with symptomatic CFA disease.

Predictors of neurological events associated with carotid artery stenting in high-surgical-risk patients: insights from the Cordis Carotid Stent Collaborative.

BACKGROUND: Comorbid and anatomic characteristics that portend higher procedural risk are well defined for carotid endarterectomy but less so for carotid artery stenting. METHODS AND RESULTS: We pooled carotid stent data from 4 Cordis-sponsored trials (n=2104) with similar patient cohorts and end point determination to identify predictors of neurological death or stroke within 30 days of the procedure. Median age was 74 years (24% >80 years), 36% were women, and 24.2% were symptomatic in the previous 6 months. There were 88 (4.2%) neurological deaths or strokes at 30 days. Among symptomatic patients, the risk of adverse neurological outcome declined with increasing time between the incident neurological event and carotid stent procedure. In a logistic regression model that included preprocedural and procedural variables, significant multivariable predictors of 30-day neurological death or stroke were older age (continuous), black race, angiographically visible thrombus in symptomatic patients, procedural use of glycoprotein IIb/IIIa inhibitors, procedural transient ischemic attack, final residual stenosis >30%, and periprocedural use of protamine or vasopressors. CONCLUSIONS: In this pooled analysis, a number of preprocedural and procedural factors predicted higher risk of stroke and neurological death within 30 days of a carotid stent procedure. Identification of such predictors may help to guide patient selection and further refine procedural technique.

Endovascular stenting for vertebral artery stenosis.

OBJECTIVES: The aim of this study was to demonstrate the safety and long-term durability of catheter-based therapy for symptomatic vertebral artery stenosis (VAS). BACKGROUND: Symptomatic VAS carries with it a 5-year 30% to 35% risk of stroke. The 2-year mortality approaches 30% for medically managed strokes involving the posterior circulation. Surgical bypass is rarely performed, due to high morbidity and mortality. Endovascular revascularization with primary stenting offers an attractive treatment option for these patients. METHODS: One-hundred five consecutive symptomatic patients (112 arteries, 71% male) underwent stent placement for extracranial (91%) and intracranial (9%) VAS from 1995 to 2006. Fifty-seven patients (54%) had bilateral VAS, 71 patients (68%) had concomitant carotid disease, and 43 patients (41%) had a prior stroke. RESULTS: Procedural and clinical success was achieved in 105 (100%) and 95 (90.5%) patients, respectively. One-year follow-up was obtained in 87 (82.9%) patients, of which 69 patients (79.3%) remained symptom-free. At 1 year, 6 patients (5.7%) had died and 5 patients (5%) had a posterior circulation stroke. Target vessel revascularization occurred in 7.4% at 1 year. At a median follow-up of 29.1 months (interquartile range 12.8 to 50.9 months), 13.1% underwent target vessel revascularization, 71.4% were alive, and 70.5% remained symptom-free. CONCLUSIONS: In experienced hands, stenting for symptomatic VAS can be accomplished with a very high success rate (100%), with few periprocedural complications, and is associated with durable symptom resolution in the majority (approximately 80%) of patients. We conclude that endovascular stenting of vertebral artery atherosclerotic disease is safe and effective compared with surgical controls and should be considered first-line therapy for this disease.

Acute stroke intervention by interventional cardiologists.

OBJECTIVES: To report the technical success and clinical outcomes of catheter-based therapy (CBT) for acute ischemic stroke in patients ineligible for intravenous thrombolysis. BACKGROUND: Acute ischemic stroke is common but undertreated. CBT for acute ischemic stroke is a therapeutic option in selected patients who are not candidates for intravenous thrombolysis. METHODS: Consecutive stroke patients who were ineligible for intravenous thrombolysis and underwent CBT were identified by retrospective chart review. Demographic information, National Institutes of Health Stroke Scale (NIHSS), procedural characteristics, and clinical outcomes during hospitalization and at 90 days follow up were collected. Experienced interventional cardiologists with the consultative support of stroke neurologists were on call for acute strokes. RESULTS: A total of 33 acute ischemic stroke patients underwent emergency cerebral angiography, with 26 patients undergoing CBT. Successful "culprit" artery recanalization was achieved in 23 (88%) of the 26 patients. In-hospital adverse events occurred in 4 (15%) patients, with intracerebral hemorrhage (ICH) (12%) representing the most common adverse event. The baseline NIHSS for patients who underwent intervention was 16.5 +/- 9.9 (median 16) and improved significantly to 9.9 +/- 8.7 (median 9) (P < 0.001) at hospital discharge. A modified Rankin score of two or less (indicating mild disability) was achieved in half (n = 13) of the CBT treated patients. All cause mortality at 90 days was 8% (2/26). CONCLUSIONS: In selected patients, CBT provided by qualified interventional cardiologists supported by stroke neurologists, offers a safe and effective option for patients with acute stroke who are not eligible for intravenous thrombolysis.

Carotid artery stent placement is safe in the very elderly (> or =80 years).

BACKGROUND: Carotid artery stent (CAS) placement is an alternative to carotid endarterectomy (CEA) for stroke prevention. Clinical adoption of CAS depends on its safety and efficacy compared to CEA. There are conflicting reports in the literature regarding the safety of CAS in the elderly. To address these safety concerns, we report our single-center 13-year CAS experience in very elderly (> or =80 years of age) patients. METHODS: Between 1994 and 2007, 816 CAS procedures were performed at the Ochsner Clinic Foundation. Very elderly patients, those > or =80 years of age, accounted for 126 (15%) of all CAS procedures. Independent neurologic examination was performed before and after the CAS procedure. RESULTS: The average patient age was 82.9 +/- 2.9 years. Almost one-half (44%) were women and 40% were symptomatic from their carotid stenoses. One-third of the elderly patients met anatomic criteria for high surgical risk as their indication for CAS. The procedural success rate was 100% with embolic protection devices used in 50%. The 30-day major adverse coronary or cerebral events (MACCE) rate was 2.7% (n = 3) with all events occurring in the symptomatic patient group [death = 0.9% (n = 1), myocardial infarction = 0%, major (disabling) stroke = 0.9% (n = 1), and minor stroke = 0.9% (n = 1)]. CONCLUSION: Elderly patients, > or =80 years of age, may undergo successful CAS with a very low adverse event rate as determined by an independent neurological examination. We believe that careful case selection and experienced operators were keys to our success.

Catheter-based treatment of the subclavian and innominate arteries.

OBJECTIVES: We report outcomes in patients undergoing catheter-based intervention for symptomatic subclavian and innominate artery (S/IA) atherosclerosis. BACKGROUND: Symptomatic S/IA obstructive lesions have traditionally been treated with open surgical revascularization. Catheter-based endovascular therapies reduce the morbidity and mortality associated with surgery in many vascular beds. METHODS: Between December 1993 and May 2006, 170 patients underwent primary stent placement in 177 S/IA arteries. Indications for revascularization included arm ischemia (57%), subclavian steal syndrome (37%), coronary-subclavian steal syndrome (21%), and planned coronary bypass surgery with the involved internal mammary artery (8%). RESULTS: Technical success was achieved in 98.3% (174/177) arteries, including 99.4% for stenotic lesions (155/156) and 90.5% for occlusions (19/21). There were no procedure-related deaths and one stroke (0.6%, 1/170). Follow-up was obtained in 151 (89%) patients at 35.2 +/- 30.8 months, with a target vessel revascularization rate of 14.6% (23/157). At last follow-up, 82% (124/151) of all treated patients remained asymptomatic with a primary patency of 83% and a secondary patency of 96%. CONCLUSIONS: Catheter-based revascularization with stents for symptomatic S/IA lesions is safe and effective with excellent patency rates and sustained symptom resolution in the majority (>80%) of patients over 3 years of follow-up. Percutaneous primary stent therapy is the preferred method of revascularization in patients with suitable anatomy.

Optimal treatment of renal artery in-stent restenosis: repeat stent placement versus angioplasty alone.

OBJECTIVE: We investigated whether repeat renal artery stent placement compared with treatment with balloon angioplasty alone results in better patency in patients presenting with renal artery in-stent restenosis (ISR). BACKGROUND: Although stent placement for renal artery stenosis has been demonstrated to be superior to balloon angioplasty for "de novo" renal artery lesions, the optimal therapy for ISR remains unclear. METHODS: Between January 1997 and August 2006, 34 consecutive patients (41 renal arteries) with ISR were treated at the discretion of the operator with balloon angioplasty or repeat stent placement. Quantitative angiography was performed before and immediately after intervention and at follow-up. Angiographic follow-up was obtained for clinical indications in 75% of lesions and routine noninvasive follow-up imaging was obtained in 95% of lesions. RESULTS: Repeat renal artery stent placement demonstrated improved patency compared with balloon angioplasty alone with a 58% reduction in recurrent ISR (29.4% vs. 71.4%, P = 0.02) and a 30% reduction in follow-up diameter stenosis (41% vs. 58.2%, P = 0.03). The repeat stent group also had better secondary patency (P = 0.05) and a greater freedom from repeat ISR (P = 0.01) when compared with balloon angioplasty alone. There was a trend favoring repeat stent placement for cumulative freedom from target vessel revascularization (TVR) (P = 0.08). CONCLUSIONS: Repeat stent placement appears to result in superior patency compared with balloon angioplasty alone for the treatment of renal ISR.

Interventional stroke therapy: current state of the art and needs assessment.

The primary therapeutic strategy for ischemic stroke, as for MI patients, is early reperfusion. Improvement in stroke treatment will require dedicated stroke centers to emulate MI quality indicators such as minimizing the "door-to-balloon time". A critical element in achieving this goal will be organizing the existing multidisciplinary pool of carotid interventionalists to provide the endovascular component of the acute care for ischemic stroke patients.