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Members of a Roma (Gypsy) family with hereditary motor and sensory peripheral neuropathy (HMSN) and concomitant auditory and vestibular cranial neuropathies were identified in Kocevje, Slovenia. The illness begins in childhood with a severe and progressive motor disability and the deafness is delayed until the second decade. There are no symptoms of vestibular dysfunction. The family structure is consistent with an autosomal recessive pattern of inheritance and the genetic locus for the disorder is linked to the same region of chromosome 8q24 as other Roma families with HMSN and deafness from Lom, Bulgaria (HMSN-Lom). The present study shows that the deafness is caused by a neuropathy of the auditory nerve with preserved measures of cochlear outer hair cell function (otoacoustic emissions and cochlear microphonics) but absent neural components of auditory brainstem potentials. The hearing loss affects speech comprehension out of proportion to the pure tone loss. Vestibular testing showed absence of caloric responses. Physiological and neuropathological studies of peripheral nerves were compatible with the nerve disorder contemporaneously affecting Schwann cells and axons resulting in both slowed nerve conduction and axonal loss. Genetic linkage studies suggest a refinement of the 8q24 critical region containing the HMSN-Lom locus that affects peripheral motor and sensory nerves as well as the cranial auditory and vestibular nerves.

The role of low-molecular-weight heparins (LMWHs) in the management of stent thrombosis, although expected to produce fewer hemorrhagic complications than warfarin anticoagulation regimens, is poorly defined. The ENoxaparin and TIClopidine after Elective Stenting (ENTICES) trial was designed to compare a combination of a LMWH (enoxaparin), ticlopidine, and aspirin with the conventional warfarin anticoagulant treatment in patients who received coronary stents, in an effort to decrease stent thrombosis and ischemic clinical events. The results show that the enoxaparin regimen produced significantly fewer clinical events and vascular complications than the conventional warfarin anticoagulant regimen. [ABSTRACT FROM AUTHOR]

Although coronary stenting has been shown to be effective, retrospective studies have suggested that stents do not provide better results than angioplasty in small coronary arteries. We sought to examine procedural, in-hospital, and long-term outcomes of patients undergoing small-vessel stenting with Palmaz-Schatz stents hand-crimped on a balloon catheter <3 mm in diameter. We retrospectively analyzed the outcomes of 117 patients who underwent this type of coronary stent implantation at Duke University Medical Center between January 1, 1997 and May 30, 1998. The clinical indications for percutaneous revascularization included unstable angina in 67.5% of patients, acute myocardial infarction in 4.3%, postinfarct angina in 3.4%, silent ischemia in 3.4%, and stable angina in 1% of patients. Quantitative angiographic analysis was performed immediately before angioplasty and after stent implantation. Stents were used for elective indications in 24%, for suboptimal angiographic result in 61.5%, and for abrupt and/or threatened closure in 14.5% of patients. Reference vessel diameter was similar before and after the procedure. Minimum luminal diameter increased from 0.63 to 2.35 mm, an acute gain of 1.72+/-0.43 mm. Percent stenosis decreased from 74.2% to 4.7%. The clinical composite of death (n = 1, 1%), nonfatal myocardial infarction (n = 6, 5.1%), and revascularization (n = 1, 1%) occurred in-hospital in only 8 patients (6.8%), resulting in clinical procedure success in 109 patients (93%). Our data suggest that stents designed for vessels >3.0 mm can be deployed in small vessels, with a low in-hospital event rate. However, target lesion revascularization in small vessels remains high. Development of antiproliferative strategies could improve long-term outcomes for small-vessel interventions. [ABSTRACT FROM AUTHOR]

We compared the effect on platelet deposition of the glycoprotein IIb/IIIa receptor antagonist L-703,081, administered locally via a drug delivery stent, with that of a standard metal stent in a canine coronary model. There was a significant reduction in platelet deposition using the L-703,081-impregnated stent compared with the bare metal stent. This study demonstrates an alternative route of delivery of GPIIb/IIIa antagonists with potential advantages over systemic administration. [ABSTRACT FROM AUTHOR]

This single-center review of a consecutive series of patients requiring reexamination by angiography within 1 week of a coronary stent placement due to chest pain reveals that patients treated with a poststent anticoagulation regimen of warfarin and aspirin, and those with lower poststent deployment dilation pressures, have an increased risk of subacute stent thrombosis. Repeat cardiac catheterization within the first week after coronary artery stent implantation should be reserved for patients with significant electrocardiographic changes. [ABSTRACT FROM AUTHOR]

Objectives: We performed a multicenter, double-blind placebo-controlled trial to examine the efficacy and safety of enoxaparin in patients at high risk for stent thrombosis (ST)., Background: The optimal antithrombotic regimen for such patients is unknown., Methods: We randomized 1,102 patients with clinical, angiographic or ultrasonographic features associated with an increased risk of ST to receive either twice-daily injections of weight-adjusted enoxaparin or placebo for 14 days after stenting. All patients received aspirin and ticlopidine. The primary end point was a 30-day composite end point of death, myocardial infarction (MI) or urgent revascularization., Results: The target enrollment for the study was 2,000 patients. However, the trial was terminated prematurely at 1,102 patients after interim analysis revealed an unexpectedly low event rate. The primary outcome occurred in 1.8% enoxaparin-treated patients versus 2.7% treated with placebo (odds ratio [OR] 0.66; 95% confidence interval [CI] 0.29 to 1.5, p = 0.30); for death or MI the rates were 0.9% vs. 2.2%, respectively (OR 0.41, 95% CI 0.14 to 1.2, p =0.13); and for MI, 0.4% vs. 1.6%, respectively (OR 0.22, 95% CI 0.05 to 0.99, p = 0.04). The groups had comparable rates of major bleeding (3.3% for enoxaparin, 1.6% for placebo, p =0.08), but minor nuisance bleeding was increased with enoxaparin (25% vs. 5.1%, p < 0.001)., Conclusions: The clinical outcomes of patients at increased risk of ST are more favorable than previously reported, rendering routine oral antiplatelet therapy adequate for most. However, given its relative safety and potential to reduce the risk of subsequent infarction, a 14-day course of enoxaparin may be considered for carefully selected patients.

Objectives: To predict which patients might not require stent implantation, we identified clinical and angiographic characteristics associated with repeat revascularization after standard balloon angioplasty., Background: Stents reduce the risk of repeat revascularization but are costly and may lead to in-stent restenosis, which remains difficult to treat. Identification of patients at low risk for repeat revascularization may allow clinicians to reserve stents for patients most likely to benefit., Methods: Data from five interventional trials (5,146 patients) were pooled for analysis. We identified patients with optimal angiographic results (final diameter stenosis < or =30% and no dissection) after balloon angioplasty and determined the multivariable predictors of repeat revascularization., Results: Optimal angiographic results were achieved in 18% of patients after angioplasty. The repeat revascularization rate at six months was lower for patients with optimal results (20% vs. 26%, p < 0.001) but still higher than observed in stent trials. Independent predictors of repeat revascularization were female gender (odds ratio [OR] 1.67, p = 0.01), lesion length > or =10 mm (OR 1.62, p = 0.03) and proximal left anterior descending coronary artery lesions (OR 1.62, p = 0.03). For the 8% of patients with optimal angiographic results and none of these risk factors, the repeat revascularization and target vessel revascularization rates were 14% and 8% respectively, similar to rates after stent implantation. Cost analysis estimated that $78 million per year might be saved in the U.S. with a provisional stenting strategy using these criteria compared with elective stenting., Conclusions: A combination of baseline characteristics and angiographic results can be used to identify a small group of patients at very low risk for repeat revascularization after balloon angioplasty. Provisional stenting for these low risk patients could substantially reduce costs without compromising clinical outcomes.

A 33-year-old woman with subacute thrombosis of the distal aorta after aorto-bi-iliac stenting had local thrombolysis with reteplase in conjunction with systemic abciximab. The infusion was given as a bolus and then continuously for 14 hr by radial artery access with two selective kissing catheters. Patency of the stented segments was achieved with this technique in conjunction with resolution of her clinical symptoms.

Coronary stents reduce the rates of abrupt closure, emergency coronary artery bypass graft surgery and restenosis, but do not prevent myocardial infarction or death at six months. The financial burden of increased stent use and the difficulty in managing in-stent restenosis have provided the impetus to develop provisional stenting strategies. Patients at low risk for restenosis after balloon angioplasty may not derive additional benefit from stent implantation and may be successfully managed with percutaneous transluminal coronary angioplasty (PTCA) alone. Numerous patient, lesion and procedural predictors of restenosis have been identified. Postprocedural assessment using quantitative coronary angiography, intravascular ultrasound (IVUS), coronary flow velocity reserve (CVR) or fractional flow reserve (FFR) may further enhance the ability to predict adverse outcomes after PTCA. Several studies have been performed to investigate the feasibility of provisional stenting strategies using various modalities to identify low risk patients who could be managed with PTCA alone. An optimal or "stent-like" angiographic result after PTCA is associated with favorable clinical outcomes. Preliminary results of studies using IVUS or CVR to guide provisional stenting appear promising. Angiography alone may be inadequate to identify truly low risk patients and may need to be combined with clinical factors, assessment of recoil, IVUS or physiologic indexes. Strategies that avoid unnecessary stenting in even a small proportion of patients may have large impacts on health care costs. Provisional stenting may potentially reduce costs and rates of in-stent restenosis without compromising the quality of health care delivery.

Bailout stenting for major dissection and threatened closure has high rates of ischemic complications. We performed a randomized trial of local heparin delivery using the infusion sleeve before bailout stenting for suboptimal angioplasty results. In phase I, 20 patients were randomized to local delivery with either 40- or 100-psi infusion pressure. In phase II, 37 patients were randomized to local delivery at 100 psi or standard therapy. Local delivery succeeded in all but one patient; overall there was no significant worsening of intimal dissection. One patient treated with 100-psi drug infusion suffered a perforation after stent placement. There were no significant differences in the composite endpoint of death, MI, CABG, urgent repeat angioplasty, and stent thrombosis at 30 days (21% vs. 0%; P = 0.18). At 6 months, the rates of myocardial infarction in phase II were 27% with local delivery vs. 10% with standard treatment (P = 0.4). Local heparin delivery in dissected vessels may be associated with increased complications and should be approached with caution.

Objectives: We compared the acute and one year medical costs and outcomes of coronary stenting with those for balloon angioplasty (percutaneous transluminal coronary angioplasty) in contemporary clinical practice., Background: While coronary stent implantation reduces the need for repeat revascularization, it has been associated with significantly higher acute costs compared with coronary angioplasty., Methods: We studied patients treated at Duke University between September 1995 and June 1996 who received either coronary stent (n = 384) or coronary angioplasty (n = 159) and met eligibility criteria. Detailed cost data were collected initially and up to one year following the procedure. Our primary analyses compared six and 12 month cumulative costs for coronary angioplasty- and stent-treated cohorts. We also compared treatment costs after excluding nontarget vessel interventions; after limiting analysis to those without prior revascularization; and after risk-adjusting cumulative cost estimates., Results: Baseline clinical characteristics were generally similar between the two treatment groups. The mean in-hospital cost for stent patients was $3,268 higher than for those receiving coronary angioplasty ($14,802 vs. $11,534, p < 0.001). However, stent patients were less likely to be rehospitalized (22% vs. 34%, p = 0.002) or to undergo repeat revascularization (9% vs. 26%, p = 0.001) than coronary angioplasty patients within six months of the procedure. As such, mean cumulative costs at 6 months ($19,598 vs. $19,820, p = 0.18) and one year ($22,140 vs. $22,571, p = 0.26) were similar for the two treatments. Adjusting for baseline predictors of cost and selectively examining target vessel revascularization, or those without prior coronary intervention yielded similar conclusions., Conclusions: In contemporary practice, coronary stenting provides equivalent or better one-year patient outcomes without increasing cumulative health care costs.

Thrombus formation after intracoronary stent implantation provides a stimulus for neointimal hyperplasia and if excessive can result in stent thrombosis. We tested the hypothesis that local delivery of an antithrombin drug from a polymeric-metallic stent inhibits platelet thrombus formation. An uncoated metal slotted tube, a jellyroll slotted metal stent with an Argatroban-loaded polymeric sleeve, and a jellyroll slotted metal stent with a drug-leached polymeric sleeve were randomly deployed into the coronary arteries of eight juvenile farm swine. Platelet deposition in the stented segments was determined at 2 hr using autologous 111Indium oxime-labeled platelets. Platelet deposition was significantly less in the Argatroban-loaded stents compared to the Argatroban-leached stents (1.40 x 10(8) platelets/cm2 vs. 26.8 x 10(8) platelets/cm2; P=0.005). When corrected for differences in the metal surface area exposed to blood, platelet deposition was significantly lower in the Argatroban-loaded stent (1.74+/-1.95 x 10(8)/cm2) compared to the Argatroban-leached stent (33.5+/-39.1 x 10(8)/cm2; P=0.005) and the uncoated metal stent (36.2+/-73.3 x 10(8)/cm2; P=0.006). In this coronary stent thrombosis model Argatroban has local antithrombotic properties when delivered with a polymer-metallic stent. Improved polymeric designs may reduce risk of thrombus deposition at the site of stent implantation.

A pilot clinical study called Enoxaparin and Ticlopidine after Elective Stenting (ENTICES) was designed to determine whether the combination of enoxaparin, ticlopidine and acetylsalicylic acid (ASA) is superior to the conventional five-drug regimen routinely used after elective stent placement (warfarin, unfractionated heparin, dextran, dipyridamole and ASA). Compared with patients on conventional therapy (44), those randomly assigned to enoxaparin and ticlopidine (79) had a lower composite rate of in-hospital bleeding and vascular complications (5% versus 16%; P = 0.005), a significantly lower composite end-point rate (death, nonfatal myocardial infarction, stent thrombosis of urgent revascularization) at 30 days (5% versus 20%; P = 0.001), a significantly lower incidence of stent thrombosis in the first 30 days (0% versus 7%; P = 0.04) and the same incidence of death or repeat angioplasty at six months. The Antiplatelet Therapy versus Lovenox plus Antiplatelet Therapy for Patients with an Increased Risk of Stent Thrombosis (ATLAST) trial was subsequently designed to compare the efficacy of the combination therapy enoxaparin. ASA and ticlopidine with that of antiplatelet therapy alone after coronary stent placement in patients at increased risk of stent thrombosis. Target enrolment of 2000 patients began in December 1996 and is expected to be complete by the end of 1998. In summary, the ENTICES pilot study demonstrated that the low molecular weight heparin enoxaparin is safe and effective for use with ASA and ticlopidine for elective stent patients. The ATLAST trial should provide results on whether enoxaparin is beneficial in patients at high risk for stent thrombosis.

Secondary to the low attrition rate of internal mammary artery grafts, limited data are available on the clinical and angiographic outcome of patients who have undergone balloon angioplasty of an internal mammary artery stenosis. This study examined a consecutive series of 68 patients who underwent balloon angioplasty of an internal mammary artery graft over a 9-year period. Procedural success was achieved in 60 of 68 (88%) patients. The primary reason for procedural failure was extreme vessel tortuosity. There were no major in-hospital complications. Angiographic follow-up was obtained in 78% of the patients with an angiographic restenosis rate of 19%. The overall event-free survival in patients with an initially successful procedure was 92%. In conclusion, internal mammary artery balloon angioplasty has both an excellent initial success rate as well as a low incidence of restenosis and repeat target lesion revascularization.

Stents have been as revolutionary for the practice of coronary revascularization in recent years as was the coronary angioplasty balloon 15 years ago, but they have also been associated with a high rate of stent thrombosis. The Enoxaparin and Ticlopidine After Elective Stenting (ENTICES) trial is designed to determine the impact of a reduced anticoagulation regimen on clinical outcomes after stent deployment. Patients are randomly assigned 2:1 to enoxaparin-ticlopidine-aspirin versus the conventional warfarin regimen, and surrogate markers of platelet activation and thrombin activity are measured after 3 days. Three factors underpin ENTICES: (1) a desire to eliminate stent thrombosis, (2) a desire to reduce length of stay after stent placement by avoiding the prolonged hospitalization required with the five-drug regimen of heparin, aspirin, dipyridamole, dextran, and warfarin, and (3) a desire to reduce the bleeding complications associated with the intense anticoagulation typically used in patients receiving stents. Patients are enrolled at seven sites in the United States and include patients with recent infarctions, restenotic lesions, and lesions as large as 30 mm in length. Other trials have also addressed issues concerning anticoagulation in patients undergoing stenting. The Stent Antithrombotic Regimen Study (STARS) trial compared aspirin, aspirin plus ticlopidine, and aspirin plus warfarin in 1650 patients receiving stents. The Aspirin/Ticlopidine vs Low-Molecular Weight Heparin/Aspirin/Ticlopidine High-Risk Stent Trial (ATLAST) is comparing aspirin plus ticlopidine with enoxaparin, aspirin, and ticlopidine in a group of patients at high risk undergoing stenting. The Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial, a trial of ticlopidine, aspirin, and 12 hours of postprocedural heparin versus phenocoumaron on and aspirin after stenting in 517 patients, found a significantly lower incidence of the combined end point of death, myocardial infarction, bypass surgery, or repeated percutaneous transluminal angioplasty in the patients who received antiplatelet therapy, but the patients enrolled were not representative of the usual population undergoing stenting. New trials of stents and their sequelae should include low-molecular weight heparins and should gather cost and outcome data to satisfy capitated systems and managed care. Innovative stent designs may also permit changes in antithrombotic regimens.

Coronary angioplasty remains limited by abrupt closure and restenosis. Metallic stents are useful for suboptimal PTCA results or threatened closure and can reduce restenosis in de novo lesions. However, they are permanent devices that are used to treat a short-term problem and have only limited potential for local drug delivery. Several catheters have been designed for specific delivery of drugs or gene products. Unfortunately drug delivery efficiency and long-term retention remain problematic. To overcome these limitations and provide a scaffold for the remodeling vessel as well as a vehicle for sustained local drug delivery, bioabsorbed stents have been proposed as an alternative. This article describes the limitations of the current metallic stents, reviews the initial animal studies of polymeric stents, and proposes the biodegradable stent as a local drug delivery device to prevent restenosis and acute closure post-PTCA.

Prolonged balloon inflation with or without autoperfusion techniques is a common initial approach to major dissection or abrupt occlusion after percutaneous transluminal coronary angioplasty (PTCA). To assess such a strategy in the setting of unsuccessful angioplasty, 40 patients who underwent prolonged balloon inflations of greater than 20 minutes between January and July of 1991 after initially unsuccessful angioplasty were studied. These patients (median age 59 years) underwent PTCA for progressive or unstable angina (16[40%]), symptomatic or asymptomatic residual stenosis after myocardial infarction (10[25%]), acute myocardial infarction (3[8%]), stable angina (3[8%]), reinfarction (2[5%]), and other indications (6[15%]). The significant stenoses were primarily in the proximal and midportions of the right coronary (53%), left anterior descending (30%) and left circumflex (17%) coronary arteries. Before prolonged balloon inflation, the longest single inflation was 11 +/- 6 minutes and the total time of all inflations was 17 +/- 8 minutes (mean +/- standard deviation). Stenosis was reduced from 91 +/- 9 to 68 +/- 16% before prolonged inflation. After prolonged balloon inflation of 30 +/- 9 minutes, the residual stenosis was 47 +/- 21% (p = 0.0001 vs value before prolonged inflation). Furthermore, improvements in the appearance of filling defects or dissections, or both, occurred in 19 patients (48%). Procedural success was obtained in 32 of 40 patients (80%). Coronary bypass grafting was performed in 8 patients (20%): 4 after unsuccessful PTCA (3 emergently) and 4 electively after initially successful PTCA. Although 5 patients had creatine kinase-MB elevations greater than 20 IU/liter after the procedure, only 1 sustained a Q-wave myocardial infarction. There were no deaths in the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)