An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

PERFORMANCE 1 study: Novel carotid stent system with integrated post-dilation balloon and embolic protection device.

OBJECTIVES: The PERFORMANCE I study was designed to evaluate the safety and feasibility of the Neuroguard IEP® System, a novel carotid stent system with an integrated embolic filter and post-dilatation balloon, to treat clinically significant carotid artery stenosis. BACKGROUND: The risk of major adverse events during carotid artery stenting is comparable to carotid endarterectomy, however, the risk of minor stroke remains higher with stenting. METHODS: In total, 67 patients undergoing carotid artery stenting were enrolled at nine centers in Europe. Follow-up assessments included neurological exams, duplex ultrasound, 12-lead electrocardiogram, and cardiac enzyme analysis. The primary endpoint was the 30-day composite rate of stroke, death, and myocardial infarctions versus a prespecified performance goal. Secondary endpoints included procedure success, device success, and target lesion revascularization. RESULTS: The study population was predominantly male (74.6%) with a mean age of 69.3 ± 8.9 years and 67% of subjects met at least one criterion placing them at an elevated risk for adverse events following carotid endarterectomy. All patients were treated successfully with the study device. There were no deaths or strokes within 30 days of the index procedure. One subject (1.5%) experienced a non-ST elevation myocardial infarction at day 17. The primary endpoint was met with a 30-day major adverse events rate of 1.5% (1/67). Through 12-month follow-up, there were no strokes, neurological deaths, target lesion revascularizations, or instances of in-stent-restenosis. CONCLUSIONS: Results from this study demonstrate the Neuroguard IEP system is safe and feasible with a stroke/death rate of 0% at 30 days. A large pivotal study is currently underway.

No Mortality Signal With Stellarex Low-Dose Paclitaxel DCB: ILLUMENATE Pivotal 4-Year Outcomes.

BACKGROUND: Paclitaxel-coated balloons have shown safety and efficacy in the short- to intermediate-term; however, long-term data remain limited. OBJECTIVES: To report late safety and efficacy outcomes for a low-dose paclitaxel drug-coated balloon (DCB) compared with percutaneous transluminal angioplasty (PTA) in femoropopliteal lesions from a large randomized controlled trial (RCT). METHODS: ILLUMENATE Pivotal is a multicenter, single-blind RCT conducted across 43 US and EU centers to examine the safety and efficacy of the Stellarex DCB for the treatment of femoropopliteal disease. Assessments were recorded for all active patients at 36 and 48 months. Vital status of patients formally exited from the study was also collected. RESULTS: Primary patency through 36 months for patients treated with DCB was significantly higher compared with PTA (p=0.016). The primary safety endpoint through 36 months was 77.4% and 72.4%, respectively (p=0.377). Kaplan-Meier analysis indicated that a higher proportion of DCB subjects were event-free compared with PTA at all study visits. The rate of major adverse event (MAE) through 48 months was 32.9% in the DCB group and 37.9% in the PTA group (p=0.428). No differences in the rate of mortality were evident through 48 months of follow-up with 15.6% in the DCB group and 15.2% in the PTA group (p=0.929). CONCLUSIONS: Stellarex DCB was associated with significantly higher patency compared with PTA through 3 years with no mortality difference detected through 4 years. The data from the ILLUMENATE Pivotal RCT support the long-term safety and efficacy of the low-dose Stellarex DCB.

The RANGER II superficial femoral artery trial: 1-year results of the long lesion cohort.

BACKGROUND: The objective of the RANGER II SFA long lesion cohort analysis was to evaluate the safety and effectiveness of the Ranger drug-coated balloon (DCB) in patients with lesion lengths greater than 100 mm. METHODS: Patients from the RANGER II SFA randomized controlled trial and long balloon sub-study were included in the long lesion cohort if their baseline lesion measurement was > 100 mm and if they had been treated with a RANGER DCB. Patients had symptomatic lower limb peripheral artery disease and Rutherford classification 2-4 symptomatology. The endpoints of interest included the 12-month target lesion primary patency and freedom from major adverse events (MAEs).Additional patient outcomes including changes in Rutherford classification were also evaluated. RESULTS: A total of 129 patients met the inclusion criteria and were included in the long lesion cohort. Mean lesion length was 144.5 ± 31.7 mm. Seventy-five lesions had Peripheral Arterial Calcium Scoring System (PACSS) grades 3 (33.3%, 43/129) and 4 (24.8%, 32/129). The Kaplan-Meier estimate of the primary patency rate at 12 months was 88.0%. The rate of freedom from MAEs at 12 months was 95.1% (117/123; 95% CI: 89.7%, 98.2%); all MAEs were clinically driven target lesion revascularization (4.9%, 6/123). The 12-month mortality rate was 2.4% (3/125). CONCLUSIONS: Patients with lesions > 100 mm treated with Ranger DCBs demonstrated excellent 1-year safety and efficacy results, comparable to those of the overall RANGER II SFA randomized clinical trial. This suggests that the Ranger DCB can provide consistent results regardless of lesion length. (ClinicalTrials.gov Identifier: NCT03064126).

Directional atherectomy before paclitaxel coated balloon angioplasty in complex femoropopliteal disease: The VIVA REALITY study.

BACKGROUND: Drug coated balloon (DCB) angioplasty significantly reduces reintervention rates in patients with symptomatic femoropopliteal peripheral artery disease (PAD). However, stand-alone DCB use in long, severely calcified lesions is frequently associated with vessel recoil and/or high-grade dissections necessitating provisional stent implantation. OBJECTIVES: Assess the safety and effectiveness of a vessel preparation strategy with directional atherectomy (DA) prior to DCB angioplasty in patients with symptomatic severely calcified femoropopliteal PAD. METHODS: REALITY (NCT02850107) prospectively enrolled subjects at 13 multinational centers with 8-36 cm femoropopliteal stenoses or occlusions with bilateral vessel wall calcification treated with DA prior to DCB angioplasty. The primary effectiveness endpoint was 12-month primary patency, and the primary safety endpoint was freedom from major adverse events through 30 days. Independent angiographic and duplex core laboratories assessed outcomes and a Clinical Events Committee adjudicated events. RESULTS: A total of 102 subjects were enrolled; one lesion was treated per subject. The mean lesion length was 17.9 ± 8.1 cm, 39.0% were chronic total occlusions (mean lesion length 22.6 ± 8.6 cm); 86.2% of lesions exhibited moderate to severe bilateral calcification. Provisional stents were implanted in 8.8% (9/102) of subjects. Twelve-month primary patency rate was 76.7% (66/86) and freedom from CD-TLR rate was 92.6% (87/94). No device or procedure related deaths and one index-limb major amputation were reported. CONCLUSIONS: Plaque excision with DA in patients with symptomatic severely calcified femoropopliteal arterial disease prior to DCB angioplasty is a safe and effective treatment strategy with a low provisional stent rate.

Stellarex Drug-Coated Balloon for Treatment of Femoropopliteal Disease: Twelve-Month Outcomes From the Randomized ILLUMENATE Pivotal and Pharmacokinetic Studies.

BACKGROUND: Drug-coated balloons (DCBs) are a predominant revascularization therapy for symptomatic femoropopliteal artery disease. Because of the differences in excipients, paclitaxel dose, and coating morphologies, varying clinical outcomes have been observed with different DCBs. We report the results of 2 studies investigating the pharmacokinetic and clinical outcomes of a new DCB to treat femoropopliteal disease. METHODS: In the ILLUMENATE Pivotal Study (Prospective, Randomized, Single-Blind, U.S. Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon), 300 symptomatic patients (Rutherford class 2-4) were randomly assigned to DCB (n=200) or standard angioplasty (percutaneous transluminal angioplasty [PTA]) (n=100). The primary safety end point was freedom from device- and procedure-related death through 30 days, and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months. The primary effectiveness end point was primary patency through 12 months. In the ILLUMENATE PK study (Pharmacokinetic Study of the Stellarex Drug-Coated Angioplasty Balloon), paclitaxel plasma concentrations were measured after last DCB deployment and at prespecified times (at 1, 4, 24 hours and at 7 and 14 days postprocedure) until no longer detectable. RESULTS: In the ILLUMENATE Pivotal Study, baseline characteristics were similar between groups: 50% had diabetes mellitus, 41% were women, mean lesion length was 8.3 cm, and 44% were severely calcified. The primary safety end point was met (92.1% for DCB versus 83.2% for PTA, P=0.025 for superiority) and the primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P=0.003). Primary patency per Kaplan-Meier estimates at day 365 was 82.3% for DCB versus 70.9% for PTA (P=0.002). The rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P=0.023). Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations. Pharmacokinetic outcomes showed that all patients had detectable paclitaxel levels after DCB deployment that declined within the first hour (54.4±116.9 ng/mL to 1.4±1.0 ng/mL). CONCLUSIONS: The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifiers: NCT01858428 and NCT01912937.

Transradial carotid artery stenting using double layer micromesh stent and novel post-dilation balloon with integrated embolic protection.

OBJECTIVES: The highest rate of embolization during carotid artery stenting occurs during post-dilation. We evaluated the ability of the Paladin system (Contego Medical, Raleigh, NC), a novel PTA balloon with an integrated 40-É¥m pore filter, to collect microemboli that may pass into the cerebral circulation when used during post-dilation. METHODS: 25 symptomatic patients underwent transradial CAS using the Paladin system in conjunction with the Roadsaver (Terumo Corporation, Tokyo, Japan) micromesh stent. No additional embolic protection was used. The Paladin filters were collected following the procedure and preserved in formalin for histological analysis. The contents were evaluated for particle count and size. Subjects were followed for 30 days and evaluated for major cardiac adverse events (death, stroke and MI). Secondary endpoints included procedure success, device success, access site complications according to EASY score classification, major vascular or ischemic complications at follow up and in-stent restenosis rate evaluated with duplex ultrasound. RESULTS: Mean age of patients was 68,5 years. Type 2 aortic arch was present in 77 % of patients and type 1 and type 3 in 12 % and 11 % of patients respectively. Procedural and device success was obtained in all cases without complications. The 30-day MAE rate was 0 %. Twenty-three filters underwent histological analysis. Microscopic debris was present in 100 % of filters, and 75 % of particles were less than 100É¥m in size. The mean number of particles per filter was 3352 ± 1567 (IQR 4300-2343), and the mean number of particles between 40-100É¥m per filter was 2499 ± 1240 (IQR 3227-1575). CONCLUSION: CAS through radial approach can be safely and effectively performed using the IEP technology Paladin device and double-layer micromesh Roadsaver stent. This strategy can simplify the procedure and decrease peri-procedural complications and procedural time.

Nine-month results of the REFORM study: a prospective, single-arm, multicenter clinical study of the safety and effectiveness of the Formula™ balloon-expandable stent for treatment of renal artery stenosis.

OBJECTIVES: To evaluate the 9-month safety and effectiveness outcomes of the Formula™ balloon-expandable renal stent (Cook Medical, Bloomington, IN) for the treatment of atherosclerotic renal artery stenosis (RAS) following suboptimal angioplasty. BACKGROUND: Atherosclerotic RAS can cause hypertension and ischemic nephropathy. When clinically indicated, an interventional approach with renal angioplasty and stent implantation is the preferred method for revascularization of atherosclerotic renal artery stenoses. METHODS: The REFORM study is a prospective, multicenter, single-arm study of stent implantation following suboptimal PTRA using the Formula stent. One hundred patients with atherosclerotic ostial renal artery lesions =18 mm in length with a >50% residual stenosis following PTA were enrolled. The primary endpoint was 9-month primary patency. RESULTS: The 9-month primary patency rate was 91.7%. The 9-month major adverse event rate was 2.2%. Mean systolic blood pressure was significantly decreased at follow-up (from 150 ± 21 mm Hg at baseline to 141 ± 21 mm Hg at 9 months; P = 0.003). Mean serum creatinine (SCr) level and mean estimated glomerular filtration rate (eGFR) were not significantly different at 9 months. A clinically meaningful improvement in renal function (i.e., =25% increase in eGFR or =0.5 mg/dl decrease in SCr) was observed in 9% of patients at 1 month and 12% of patients at 9 months. A clinically meaningful decline in renal function (i.e., =25% decrease in eGFR or =0.5 mg/dl increase in SCr) was observed in only 3% of patients at 1 month and 7% of patients at 9 months. CONCLUSIONS: The Formula stent was safe and effective in treating atherosclerotic RAS following suboptimal angioplasty.

The transradial approach for carotid artery stenting.

BACKGROUND: Carotid artery stenting (CAS) is an alternative to carotid endarterectomy (CEA) for revascularization of the internal carotid artery (ICA). CAS from the femoral approach may be problematic due to peripheral vascular disease, anatomical variations of the aortic arch, and access site complications. The purpose of this study was to evaluate the right radial approach (RRA) for CAS. METHODS: A retrospective analysis of all patients who had undergone transradial (TR) CAS at two centers was performed. Demographics, the technique used to deploy the sheath in the common carotid, procedural details, results, and complications were evaluated. RESULTS: CAS was attempted from TR in 382 patients (mean age 68, 70% male). CAS was successful in 347/382 (91%) patients; 201/216 (93%) right CA, 14/16 (88%) bovine left CA, 132/150 (88%) left CA. The specific technique varied with the anatomy. Seven different carotid artery stents (51% Xact) and seven different distal embolic protection devices were used. Adverse events included two major strokes (0.6%) one of whom died, three minor strokes (1%), and no myocardial infarction at 30 days. No bleeding complications occurred although 23 (6%) of patients had asymptomatic postprocedure radial occlusion. Inadequate catheter support at the origin of the CCA was the technical cause of failure in the unsuccessful cases which were then completed from femoral access as part of the same procedure. CONCLUSION: The transradial approach is an alternative for CAS in the presence of factors that increase the risk or difficulty of femoral access.

Carotid Artery Stenting: JACC State-of-the-Art Review.

Significant advances in the field of carotid artery stenting (CAS) have occurred, including new randomized trial data, recent professional societal statements for competency, new techniques and new devices that have been developed, and perhaps most importantly, our understanding of how to better select candidates for CAS to avoid periprocedural complications. The current Centers for Medicare and Medicaid Services coverage decision regarding CAS is outdated, and our review supports our recommendation to approve CAS in selected candidates who are symptomatic with a carotid stenosis ≥50% and ≤99% and for asymptomatic patients with carotid stenosis ≥70% and ≤99% for stroke prevention. Optimized CAS strategies have allowed experienced operators to better assess procedure risk before CAS and have led to continued improvement in CAS outcomes. New technologies including enhanced embolic protection devices and dual-layered stents should result in further improvement.

Determinants of Drug-Coated Balloon Failure in Patients Undergoing Femoropopliteal Arterial Intervention.

BACKGROUND: Drug-coated balloons (DCB) are frequently used to treat femoropopliteal artery disease. However, patency loss occurs in ≥10% of patients within 12 months posttreatment with poor understanding of the underlying mechanisms. OBJECTIVES: The authors sought to investigate the determinants of DCB failure in femoropopliteal disease. METHODS: Data from randomized clinical trials (IN.PACT SFA, MDT-2113 SFA Japan) and 2 prespecified imaging cohorts of the IN.PACT Global Clinical Study were included. Influential procedural characteristics were evaluated by an independent angiographic core laboratory. The primary endpoint was DCB failure (patency loss during follow-up). Additional endpoints were binary restenosis and clinically driven target lesion revascularization. Multivariable analyses evaluated the clinical, anatomical, and procedural predictors of DCB failure. RESULTS: Included were 557 participants with single lesions and 12-month core laboratory-adjudicated duplex ultrasonography. Key clinical characteristics were as follows: mean age 68.8 years, 67.5% male, 87.6% with hypertension, 76.9% with hyperlipidemia, 40.5% with diabetes mellitus, 90.5% in Rutherford Classification Category (RCC) 2 to 3, and 9.5% in RCC 4 to 5. Average length and reference vessel diameter (RVD) were 16.37 cm and 4.66 mm, respectively; 49.7% of lesions were totally occluded. In multivariable analysis, only residual stenosis >30% was associated with patency loss, whereas residual stenosis >30% and smaller preprocedure RVD were associated with increased binary restenosis risk. RCC >3 and residual stenosis >30% were associated with increased 12-month clinically driven target lesion revascularization risk. CONCLUSIONS: Patency loss after DCB treatment was influenced by procedural and clinical factors. Residual stenosis >30%, smaller preprocedure RVD, and higher RCC may be considered predictors of increased risk of DCB failure and its components in femoropopliteal artery disease. (Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I]; NCT01175850; IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II]; NCT01566461; MDT-2113 Drug-Eluting Balloon vs. Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery [MDT-2113 SFA]; NCT01947478; IN.PACT Global Clinical Study; NCT01609296).

1-Year Results From the RANGER II SFA Randomized Trial of the Ranger Drug-Coated Balloon.

OBJECTIVES: This study sought to evaluate the safety and effectiveness of the Ranger drug-coated balloon (DCB) (paclitaxel dose density 2 µg/mm2) for treating superficial femoral artery or proximal popliteal artery lesions. BACKGROUND: Paclitaxel-coated balloon treatment prevents reinterventions, but dose and coating characteristics differ among balloons and necessitate discrete confirmation of safety and effectiveness. METHODS: Patients with symptomatic lower limb ischemia (Rutherford classification 2 to 4) were randomized 3:1 to treatment with the Ranger DCB or standard percutaneous transluminal angioplasty (PTA). Twelve-month primary target lesion patency, freedom from major adverse events (i.e., target lesion revascularization, major amputations, death within 1 month of the index procedure), and patient outcomes were analyzed. RESULTS: Mean lesion length was 82.5 ± 48.9 mm for the Ranger DCB group (n = 278) and 79.9 ± 49.3 mm for the control group (n = 98). Ranger DCB was superior to PTA (82.9% [n = 194 of 234] vs. 66.3% [n = 57 of 86]) with observed 12-month primary patency rates yielding a difference of 16.6% (95% confidence interval: 5.5% to 27.7%; p = 0.0013). Noninferior freedom from major adverse events (94.1% [n = 241 of 256] vs. 83.5% [n = 76 of 91]) was demonstrated with a difference of 10.6% (95% confidence interval: 2.5% to 18.8%; noninferiority p < 0.0001). Primary patency rate curves showed significant separation by Kaplan-Meier analysis (log-rank p = 0.0005), with rates of 89.8% and 74.0% estimated at day 365 for the Ranger DCB and PTA cohorts, respectively. CONCLUSIONS: The low-dose Ranger DCB demonstrated significantly better effectiveness than standard PTA through 1 year and a good safety profile. (Ranger™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty [RANGER II SFA]; NCT03064126).

Double Filtration During Carotid Artery Stenting Using a Novel Post-Dilation Balloon With Integrated Embolic Protection.

OBJECTIVES: This study evaluated the safety and performance of the Paladin System, a novel angioplasty balloon with an integrated embolic protection filter designed to increase embolic protection during post-dilation. BACKGROUND: The risk of major adverse events during carotid artery stenting (CAS) is equivalent to carotid endarterectomy. However, the risk of minor stroke remains higher with CAS. Much of this risk occurs during post-stent dilation. METHODS: A total of 106 patients were enrolled in 5 centers in Germany. The study's primary endpoint was all-cause death, myocardial infarction, and stroke at 30 days post-procedure. Pre- and post-procedural diffusion-weighted magnetic resonance imaging evaluated new ischemic lesions in 30 subjects. Filter histomorphometric analysis was performed in 23 patients. Retrospective analyses compared outcome rates to historical controls. RESULTS: Device and procedural success rates were 100%. The combined major adverse event rate (death, myocardial infarction, and stroke) at discharge and at 30 days was 0% and 1.0%, respectively. The single adverse event was a stroke, which occurred at day 12 and was believed unrelated to the device or procedure. New ischemic lesions were found in 11 (36.7%) patients in the diffusion-weighted magnetic resonance imaging subset. New ipsilateral lesions were seen in 9 (30.0%) patients. Mean lesion volume per patient was 0.010 cm3. Debris was present in all filters, and approximately 90% of captured particles were <100 µm. CONCLUSIONS: Use of the Paladin System for post-stent dilation during CAS appears safe, and it may effectively decrease the number of embolic particles reaching the brain, which may help reduce the risk of procedure-related stroke. (A Multi-Center Study to Evaluate Acute Safety and Clinical Performance of Paladin® Carotid Post-Dilation Balloon System With Integrated Embolic Protection; NCT02501148).

Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the Femoropopliteal Arteries: Long-Term Results of the IN.PACT SFA Randomized Trial.

BACKGROUND: Randomized controlled trials have reported favorable 1-year outcomes with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral arterial disease when compared with standard percutaneous transluminal angioplasty (PTA). Evidence remains limited on the durability of the treatment effect with DCBs in the longer term. METHODS AND RESULTS: IN.PACT SFA is a single-blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with symptomatic (Rutherford 2-4) femoropopliteal lesions up to 18 cm in length. Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month assessments included primary patency, freedom from clinically driven target lesion revascularization, major adverse events, and functional outcomes. At 36 months, primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; log rank P<0.001). The rates of clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002) for the DCB and PTA groups, respectively. Functional outcomes were similarly improved between treatment groups even though subjects in the DCB group required significantly fewer reinterventions versus those in the PTA group (P<0.001 for target lesion revascularization, P=0.001 for target vessel revascularization). There were no device- or procedure-related deaths as adjudicated by an independent Clinical Events Committee. CONCLUSIONS: Three-year results demonstrate a durable and superior treatment effect among patients treated with DCB versus standard PTA, with significantly higher primary patency and lower clinically driven target lesion revascularization, resulting in similar functional improvements with reduced need for repeat interventions. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for IN.PACT SFA phase II in the United States.

Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation.

OBJECTIVES: The aim of this study was to determine whether angiographically silent early coronary intimal thickening could predict long-term morbidity and mortality. BACKGROUND: Although intravascular ultrasound (IVUS) is widely used to detect early transplant coronary disease, its prognostic significance has not been well defined. METHODS: The study cohort consisted of 143 patients who underwent early multivessel (2.1 +/- 0.7 arteries/patient) IVUS examination 1.0 +/- 0.5 month and 12.0 +/- 1.0 month after transplantation. The change in intimal thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly progressive vasculopathy was defined as the change in intimal thickness >/=0.5 mm. Patients were followed for a primary end point of all-cause mortality and a secondary composite end point of mortality and nonfatal myocardial infarction (MI). Angiographic disease, defined as any >/=50% diameter stenosis, was assessed in 126 patients. RESULTS: Intravascular ultrasound at one year demonstrated rapid progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly progressive vasculopathy died, as compared with those without (26% vs. 11%, p = 0.03). Death and MI also occurred more frequently among those with rapid progression than in those without it (51% vs. 16%, p < 0.0001). There was no significant difference in outcome in patients with and without donor-transmitted lesions. Angiographic disease was found in 11 (22%) of 50 patients with and in 2 (2.1%) of 76 patients without (p = 0.003) rapidly progressive vasculopathy. The IVUS-defined rapid progression correlated highly with future development of angiographic disease (p = 0.0005). CONCLUSIONS: Rapidly progressive vasculopathy by IVUS, defined as an increase of >/=0.5 mm in intimal thickness within the first year after transplantation, is a powerful predictor of all-cause mortality, MI, and angiographic abnormalities. Accordingly, such patients may be candidates for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.

Evaluating the optimal activated clotting time during carotid artery stenting.

Carotid artery stenting is an alternative to carotid endarterectomy for patients at high risk for surgery for carotid artery stenosis. Although unfractionated heparin is routinely used, there are no published data evaluating the optimal activated clotting time during carotid stenting. In a retrospective analysis of 605 patients who underwent carotid stenting using unfractionated heparin at the Cleveland Clinic Foundation, the optimal peak procedural activated clotting time associated with the lowest combined incidence of death, stroke, or myocardial infarction was 250 to 299 seconds.

Association between apolipoprotein E alleles and calcific valvular heart disease.

BACKGROUND: Studies on apolipoprotein E (apoE) alleles have reported an increased risk of coronary heart disease in patients with the apoE4 allele. Given the risk factor and histological similarities between coronary and calcific valvular heart disease (aortic stenosis [AS] and mitral annular calcification [MAC]), we postulated that apoE alleles might be associated with the development of these valvular lesions. METHODS AND RESULTS: We evaluated the association between apoE alleles and calcific valvular lesions in 802 patients undergoing transthoracic echocardiography using logistic regression analyses. No difference was noted in genotype distribution (P=0.59) or prevalence of apoE4 between those with or without MAC (30% versus 27%, respectively; P=0.57). Compared with patients without AS, the genotype distribution of patients with AS differed significantly (P=0.03), with increasing prevalences of the apoE 4 allele (27% in those without versus 40% in those with AS; P=0.01). In multivariate analyses adjusting for age, gender, low-density lipoprotein cholesterol levels, and coronary artery disease, increasing age and the apoE4 allele were significant independent predictors of AS (odds ratio, 1.94; 95% confidence interval, 1.01 to 3.71; P=0.046), whereas the apoE4 allele was not predictive of MAC. CONCLUSIONS: These findings support extension of the importance of the apoE4 allele beyond atherosclerosis and Alzheimer's disease to calcific AS.

Severe bilateral carotid stenosis: the impact of ipsilateral stenting on Doppler-defined contralateral stenosis.

OBJECTIVES: The study examined the effect of carotid stenting (CS) on contralateral carotid Doppler-defined degree of stenosis. BACKGROUND: Patients with carotid disease are frequently referred for carotid revascularization (carotid endarterectomy [CEA] or CS) based on the results of carotid duplex studies. Although a drop in flow velocities in the contralateral carotid has been described after CEA, the effect of ipsilateral stenting on contralateral velocities has not been defined. METHODS: A total of 104 consecutive patients underwent CS and were divided into two cohorts, those with unilateral stenosis, and those with bilateral stenosis. Doppler-defined pre-procedural peak systolic velocities (PSV) and end-diastolic velocities (EDV) in the contralateral carotid were compared with the post-procedural velocities. Post-procedural angiographic stenoses were compared with post-procedural duplex-defined stenoses. RESULTS: Among patients with bilateral stenosis, after ipsilateral stenting there was a drop in the contralateral PSV and EDV of 60.3 cm/s (p = 0.005) and 15.1 cm/s (p = 0.03), respectively. There was no change in the contralateral velocities in patients with unilateral stenosis. Among patients with > or =60% stenosis by duplex in the contralateral carotid, 20% dropped to a lower classification of contralateral stenosis after ipsilateral stenting. Furthermore, 71% of patients with significant contralateral stenosis by duplex pre-stenting did not have significant stenosis by angiography. CONCLUSIONS: Patients with bilateral carotid disease may have elevated Doppler flow velocities in the contralateral carotid resulting in an artifactually high grade of stenosis. After ipsilateral carotid revascularization, such patients should have a repeat Doppler of the contralateral carotid to assess the true grade of stenosis.

Symptomatic patients have similar outcomes compared with asymptomatic patients after carotid artery stenting with emboli protection.

In a single-center cohort of 174 consecutive patients, we sought to evaluate whether the use of emboli protection devices (EPDs) results in equivalent rates of adverse events in symptomatic and asymptomatic patients after carotid artery stenting (CAS) with EPDs. Death or stroke occurred in 3.3% in the symptomatic group and in 3.5% of the asymptomatic group at 30 days (p = NS). At 6 months, there was also no significant difference in the rate of stroke or death between the groups. Unlike surgical revascularization, symptomatic patients did not have a greater risk for stroke and death compared with asymptomatic patients after CAS with EPDs.

Relation of albumin/creatinine ratio to C-reactive protein and to the metabolic syndrome.

We hypothesized that the association of high sensitivity C-reactive protein (CRP) with urinary albumin excretion (UAE) is predominately mediated through its correlation with the metabolic syndrome. Serum CRP and urine albumin:creatinine ratios (ACR) from 720 preventive cardiology patients were analyzed to estimate age- and gender-adjusted relative risk of high CRP and metabolic syndrome for high ACR. These data demonstrate that CRP independently predicts the presence of UAE, a marker of endothelial dysfunction.