Of mixed vegetables and cardiac arrhythmias - Digitalis purpurea confused with Borago officinalis: A case series of accidental digitoxin intoxications.

We present the case series of two women aged 35 and 60 years who presented to our emergency department with severe vomiting, nausea, and malaise. Their symptoms started approximately 2 h after the ingestion of home-made mixed vegetables with freshly picked vegetables and leaves from the patients' garden, of which one was supposed to be borage. An electrocardiogram revealed diffuse ST-segment depression with down-up sloping in both patients. We supposed an accidental confusion of wild borage (Borago officinalis) with foxglove (Digitalis purpurea). Both patients were subsequently admitted to the intermediate-care-unit for close monitoring and continuous activated charcoal administration. Digitoxin serum concentrations were elevated in both patients (40.9 and >50 ng/ml, respectively - reference therapeutic range 8-18 ng/ml). The younger woman, despite the relatively lower serum digitoxin concentrations, presented a single episode of advanced atrioventricular block and long-lasting sinus bradycardia. Both showed a complete recovery. Although not uncommon, our case series reiterates the fact that such plant misclassifications are potentially life-threating and warrant the treating physicians' full attention. Learning objective: Plant poisoning is a frequent reason for consultation of poison information centers and may result in life-threatening cardiac arrhythmias. Confusion of foxglove leaves (Digitalis purpurea) with borage leaves (Borago officinalis L.), which is a popular food ingredient for mixed salads, is not uncommon. Without a dedicated medical history, such cases are difficult to diagnose and warrant the treating physicians' full attention and the involvement of a local poison information center.

Prognostic value of mild-to-moderate pulmonary hypertension in patients with severe aortic valve stenosis undergoing aortic valve replacement.

BACKGROUND: Optimal timing of elective aortic valve replacement (AVR) for severe aortic stenosis (AS) is challenging. Hence, a sensitive marker in AS patients indicating increasing risk after AVR would be of great clinical value. In the present study, we hypothesized that mild-to-moderate pulmonary hypertension (PH) assessed prior to AVR is a sensitive marker for adverse events in patients after successful AVR. METHODS: We enrolled 200 consecutive patients with severe AS undergoing AVR. Among them, 176 patients (88%) were symptomatic. Patients were divided according to systolic pulmonary artery pressure (PAP(sys)) into three groups: no PH (PAP(sys) <30 mmHg), mild-to-moderate PH (PAP(sys) ≥30 and PAP(sys) <60 mmHg) and severe PH (≥60 mmHg). Multivariable analyses were adjusted for age and gender and included PH, left ventricular ejection fraction ≤35%, renal insufficiency and logistic EuroSCORE ≥20%. Primary endpoint was death of any cause within 5 years after AVR. RESULTS: During follow-up, 23 patients died (cumulative 5-year mortality rate 14.6%). Patients without (n = 78), mild-to-moderate (n = 99) and severe PH (n = 23) had 5-year mortality rates of 2.6, 15.2 and 26.1% (p = 0.001). PAPsys ≥30 mmHg yielded an excellent level of sensitivity of 92.8%. On multivariable analysis, mild-to-moderate PH was the only independent risk factor (hazard ratio 4.9, 95% confidence interval 1.1-21.8). CONCLUSIONS: In patients with severe AS undergoing AVR, mild-to-moderate PH is a strong and independent predictor of late mortality. Conversely, patients with normal PAP(sys) have an extremely good prognosis.

Best way to revascularize patients with main stem and three vessel lesions: patients should undergo PCI!

The optimal revascularization strategy for multivessel disease is under controversial discussion for long time. Until now, technical innovations have been faster than performance of clinical trials, making results of randomized studies outdated at the time of appearance. Recently, the SYNTAX trial has been published, which compared drug elutings stents (DES) implantation with Coronary artery bypass graft (CABG) patients with multivessel or left main disease in a clinically stable population. Overall, CABG was superior with respect to the clinical endpoint of death, myocardial infarction, stroke, or revascularization. However, the difference is driven by the "weakest" end point, namely repeated revascularization, whereas combined "hard" events did not demonstrate a difference. More detailed analysis demonstrates that only patients with most complex coronary anatomy gain definite benefit from CABG. In addition, SYNTAX demonstrated that left main disease is no longer a domain of CABG, since DES implantation revealed comparable results, as long as there is no concomitant multivessel disease. Regardless the results of SYNTAX, one should not forget that SYNTAX represents only a minority of daily patients in a catheterization laboratory, excluding patients with one- or two-vessel disease and those with an acute coronary syndrome. Especially in the latter, percutaneous coronary intervention has demonstrated to improve prognosis.

Early but not late stent thrombosis is influenced by residual platelet aggregation in patients undergoing coronary interventions.

AIMS: Recent studies suggest a relevant association of post-interventional residual platelet aggregation (RPA) under therapy with oral platelet inhibitors and the occurrence of atherothrombotic events. The influence of post-interventional RPA on the incidence of stent thrombosis (ST) has not been sufficiently evaluated in consecutive unselected cohorts of percutaneous coronary intervention (PCI) patients. The aim of this observational study was to investigate the impact of RPA on the incidence of ST within 3 months in patients treated with dual antiplatelet therapy. METHODS AND RESULTS: The study population included a consecutive cohort of 1019 patients treated with PCI [n = 741 bare-metal stent (BMS) and n = 278 drug-eluting stent (DES)] due to symptomatic coronary artery disease. Residual platelet activity was assessed by adenosine disphosphate (20 micromol/L)-induced PA after 600 mg clopidogrel loading dose. Maximum RPA was measured as peak of aggregation, final RPA was measured 5 min after addition of agonist. The primary endpoint was the occurrence of ST within 3 months defined according to academic research consortium (ARC) criteria. Final and maximum RPA were independent predictors of ST after 3 months. In secondary analysis, the observed effects were independently associated with early ST (HR 1.05, 95% CI 1.01-1.08 and HR 1.05, 95% CI 1.01-1.09, P < 0.01, respectively). However, incidence of 3-month late stent thrombosis (LAT) was not influenced by post-interventional RPA in multivariable analysis. CONCLUSION: Post-interventional RPA is associated with the occurrence of early ST in patients treated with either BMS or DES; however, there is no predictive value of RPA for the incidence of 3-month LAT, suggesting the involvement of other possible mechanisms like discontinuation of antiplatelet therapy.

Massive haemoptysis in an intravenous drug user with infective tricuspid valve endocarditis.

Major causes of morbidity in intravenous drug users are infections. In infective endocarditis, the tricuspid valve is mainly involved. Masses can cause septic embolisms and, in rare cases, they are associated with mycotic aneurysms of pulmonary arteries that lead to severe haemorrhage. We report the case of a young woman with a history of intravenous drug abuse and prolonged infective tricuspid valve endocarditis. Initially, echocardiography showed large masses on the anterior leaflet of the tricuspid valve and severe tricuspid regurgitation; blood cultures revealed staphylococcus and streptococcus species. Eight months after initial diagnosis, she presented with severe haemoptysis and fever. CT revealed a ruptured mycotic aneurysm of the right pulmonary artery. Lobectomy was performed immediately. Postoperatively, the patient fully recovered. After continued antibiotic treatment, follow-up examinations showed negative echocardiographic findings and blood cultures results.

Catheter-based delivery of fluid paclitaxel for prevention of restenosis in native coronary artery lesions after stent implantation.

BACKGROUND: Stents eluting antiproliferative drugs reduce the incidence of restenosis but delay healing of the vascular wall. We assessed the safety and efficacy of catheter-based local delivery of fluid paclitaxel in patients with coronary de novo stenoses after implantation of a bare metal stent. METHODS AND RESULTS: We conducted a prospective, randomized trial comparing the local delivery of fluid paclitaxel after bare metal stent implantation (group I) with the implantation of a bare metal stent (group II) and the implantation of a paclitaxel-eluting stent (group III) in 204 patients. The primary end point was in-stent late lumen loss. Secondary end points included binary restenosis rate >50%, minimal lumen diameter, diameter stenosis, and a composite clinical end point (major adverse cardiac events and revascularization of the target lesion) 6 months after intervention. At 6 months, angiography showed an in-stent late lumen loss of 0.61+/-0.44 mm in group I versus 0.99+/-0.72 mm in group II (I versus II, P=0.0006) and 0.44+/-0.48 mm in group III (noninferiority of I versus III, P=0.023). The 1-sided 95% CI for the true difference of the means of in-stent late lumen loss in groups I and III was -infinity to 0.3174188. The cumulative overall rate of major cardiac events was 13.4% in group I, 26.8% in group II, and 14.9% in group III. Target lesion revascularization rate was 13.4% (group I), 22.1% (group II), and 13.4% (group III). CONCLUSIONS: Additional antiproliferative treatment of de novo lesions in native coronary arteries with catheter-based delivery of fluid paclitaxel after bare metal stenting was safe and significantly reduced neointimal proliferation, restenosis, and clinical events compared with bare metal stent implantation alone.

Risk stratification by adenosine stress cardiac magnetic resonance in patients with coronary artery stenoses of intermediate angiographic severity.

OBJECTIVES: The purpose of this study was to determine the role of adenosine stress cardiac magnetic resonance (CMR) for risk stratification in patients with coronary artery stenoses of intermediate angiographic severity. BACKGROUND: Coronary angiography only provides a morphological description of coronary lesions. As the patient's prognosis is closely related to the functional significance of angiographically detected coronary lesions, a functional assessment is desirable in patients with coronary artery stenoses of intermediate severity. METHODS: Myocardial perfusion measurements at rest and adenosine stress were performed on 81 patients (75.6% male, mean age 64.2 years) with stable angina pectoris (AP) and coronary artery stenoses of intermediate angiographic severity (50% to 75%). Regardless of the CMR result, all patients were treated conservatively with an intensified medical treatment, and a follow-up was performed after 18 +/- 8 months and 30 +/- 8 months. The primary end point was defined as a major adverse cardiac event (MACE): all-cause death, stroke, acute coronary syndrome; the secondary end point was defined as target vessel revascularization. Furthermore, AP and dyspnea were evaluated. RESULTS: After the follow-up period of 30 +/- 8 months, 9 patients with perfusion deficit (PD) suffered from MACE, whereas no MACE occurred among the 36 patients without PD (p = 0.014). Among patients who had MACE, the number of ischemic segments (2.3 +/- 1.6 vs. 1.4 +/- 1.6, p = 0.0025) was significantly higher, whereas the number of delayed enhancement segments did not differ (1.4 +/- 1.6 vs. 1.6 +/- 2.3, p = 0.4). Target vessel revascularization was required in 38% of patients with PD and 6% of patients without PD (p = 0.005). In addition, the percentage of freedom from AP and dyspnea at the follow-up after 18 +/- 8 months was significantly lower among patients without perfusion deficit (69.4% vs. 15.6%; p = 0.0001). After a follow-up period of 30 +/- 8 months, the rate of AP (11.1% vs. 8.3%, p = 0.33) as well as the percentage of patients free of symptoms was similar in both groups (77.8% vs. 88.9%, p = 0.82). CONCLUSIONS: Adenosine stress CMR may help to identify patients at risk who benefit from intensified medical treatment and close follow-up.

Successful thrombolysis of mechanical mitral valve prosthesis in a patient with cardiogenic shock.

A 48-year-old woman with cardiogenic shock was admitted to a nearby hospital. Her medical history included mechanical replacement of her mitral valve 4 years previously in Russia because of rheumatic stenosis. On admission, her international normalised ratio (INR) was significantly reduced below the therapeutic limit. A severe stenosis of the valve prosthesis was identified by transthoracic and transoesophageal echocardiography and the patient was transferred to our university hospital for discussion of an immediate therapeutic procedure and to ensure cardiac surgical backup. Here, the patient's poor clinical status led to the decision for a non-routine treatment: a successful series of intravenous thrombolysis with alteplase. Clinical symptoms and echocardiographic parameters improved significantly.

[Drug-eluting stents for diabetic patients. A critical appraisal of the currently available data from randomized trials]. / Drug-eluting Stents bei Patienten mit Diabetes mellitus: Eine kritische Analyse der aktuellen Datenlage aus randomisierten Studien.

BACKGROUND AND PURPOSE: Patients with coronary artery disease (CAD) and diabetes mellitus represent a peculiar high-risk population because of their specific characteristics of atherosclerotic disease. In conjunction with the diabetes-related comorbidities, percutaneous coronary intervention (PCI) often leads not only to a worse acute result but - also as compared to nondiabetics - to significantly worse long-term results due to the higher restenosis rates. The rapid introduction of effective drug-eluting stents (DES), which undoubtedly reduce the restenosis rates as compared with bare-metal stents (BMS), brought great hope of providing diabetic patients better and longer-lasting interventional solutions. This overview compiles the currently available data from randomized trials and meta-analyses. METHODS: Altogether, 86 randomized DES studies were identified in 34,677 patients. None of these with an adequate primary clinical endpoint had diabetes as an inclusion criterion. The high standard of an adequate primary clinical endpoint for comparing BMS versus DES in patients with predominantly stable CAD and de novo lesions was met by only five pivotal trials: SIRIUS (Cypher stent), TAXUS-IV, -V, -VI (Taxus stent) and ENDEAVOR II (Endeavor stent). Patients with diabetes were represented in these trials only in smaller subgroups. Three studies with a primary surrogate endpoint had diabetes as an inclusion criterion (DIABETES, SCORPIUS and ISAR-DIABETES, totaling 610 patients). The efficacy parameter TLR (target lesion revascularization) was chosen to compare these studies and the subgroup analyses. RESULTS: In the subgroup analyses for diabetic patients in the pivotal trials, TLR was reduced at the time of the primary endpoint after 9 months as compared with BMS as follows (p < 0.05): Cypher stent (279 patients): 22.3% versus 6.9%; Taxus stent (318 patients): 16.0% versus 5.2%; Endeavor stent (239 patients): 15.2% versus 7.5%. 5-year follow-up data are available only for the Cypher and Taxus stents with 33.1% versus 13.7% and 26.9% versus 13.4%. As compared with BMS, the three above-mentioned studies studies with a primary surrogate endpoint and diabetes as an inclusion criterion showed a significant reduction of TLR after 9 months of 31.3% versus 7.3% and after 8 months of 25.0% versus 5.3%, respectively. The TLR between Taxus (12.0%) and Cypher (6.4%), however, was not statistically different. Meta-analyses of 627 Cypher patients and 814 Taxus patients corroborated these findings with 1-year TLR of 24.8% versus 7.9% and 20.5% versus 8.0%. CONCLUSION: Of the 22 DES having received a CE certificate, long-term data over 5 years for patients with diabetes are available only for the Cypher and the Taxus stents. Compared with BMS, patients with diabetes and their characteristically small vessels and long lesions predominantly benefit from effective DES. The sometimes postulated differences between Cypher and Taxus in diabetic patients could not be convincingly demonstrated; larger randomized trials with a primary clinical endpoint are required for this. PCI cannot be considered a scientifically sound and evidence- based alternative to bypass surgery in diabetic patients with multivessel disease and/or unprotected left main stenosis until we have the results of the SYNTAX, COMBAT and FREEDOM trials.

Statins do not adversely affect post-interventional residual platelet aggregation and outcomes in patients undergoing coronary stenting treated by dual antiplatelet therapy.

AIMS: There are growing data suggesting a clinical relevance of residual platelet aggregation (RPA) in patients undergoing PCI. Drug-drug interaction of statins and clopidogrel has been controversially discussed in ex vivo studies and clinical trials. The aim of the present study was to investigate the effects of peri-procedural statin medication on the metabolization of aspirin and clopidogrel with regard to platelet aggregation and clinical outcome in patients undergoing coronary intervention. METHODS AND RESULTS: Patients with coronary stenting for symptomatic coronary artery disease are routinely evaluated by platelet function analysis in a monocentre registry, and for the present study, a consecutive cohort of 1155 patients were analysed. About 87.7% of the patients were treated with statins at the time of platelet function analysis. Residual platelet activity assessed by adenosine diphosphate (20 micromol/L)-induced platelet aggregation was not significantly influenced by statin treatment. Nor the significant effects of CYP3A4-metabolization pathway on post-treatment aggregation were recorded, although there was even a trend to lower RPA values in patients treated with CYP3A4-metabolized statins. Further, in an inter-individual analysis comparing patients treated with CYP3A4- and non-CYP3A4-metabolized statins, no time-dependent difference of clopidogrels anti-aggregatory effects was observed. Clinical follow-up of major adverse events (myocardial infarction, ischaemic stroke, death) in 991 patients within 3 months revealed no significant adverse effects of statin treatment on clinical outcome. Instead, statin treatment was independently associated with lower incidence of composite events (HR 0.44, 95% confidence interval 0.23-0.83, P = 0.01). CONCLUSION: Peri-procedural co-administration of statins does not increase the post-interventional RPA in cardiovascular patients treated with dual antiplatelet therapy and does not worsen the clinical prognosis of these patients.

Local catheter-based delivery of antithrombotic or antiproliferative drugs: a new concept for prevention of restenosis.

BACKGROUND: Drug eluting stents have reduced the incidence of restenosis after percutaneous coronary interventions significantly, but cause concern about long term safety. Local drug delivery using special application catheters is an alternative approach for intracoronary pharmacotherapy. Besides the fact, that no problematic coating as drug carrier has to be used, a local delivery independent of the stent itself by using catheter techniques offers further advantages - such as the possibility to treat the whole vessel wall, stent edges and adjacent vessel segments and not only the area close to the stent struts. METHODS AND RESULTS: We have developed a new local catheter-based delivery system for local intracoronary pharmacotherapy. An antithrombotic as well as an antiproliferative therapy concept for prevention of restenosis are presented in the manuscript. Our data show that local drug delivery of platelet glycoprotein VI and paclitaxel were effective in the reduction of thrombus formation and neointima formation in experimental animal models. CONCLUSIONS: A combination of early antithrombotic and antiatherosclerotic mechanisms may be a realistic and effective approach to minimize postinterventional thromboischemic events and neointima formation. These results may contribute to an advanced and even combined local intracoronary pharmacotherapy in near future, independent of stent coatings.

Catheter-based local antiproliferative therapy in kissing balloon technique for in-stent stenosis of coronary artery bifurcation lesions.

There is currently no promising interventional solution for in-stent stenosis in previously stented bifurcation lesions, even with drug-eluting stents. Rather than being restricted to stent struts, catheter-based local antiproliferative therapy offers the advantage of homogenous drug transfer to the whole vessel wall, and thereby allows for intracoronary pharmacotherapy without adding additional layers of metal into an already stented lesion. The newly developed GENIE catheter (Acrostak Corp, Switzerland), applied in the kissing balloon technique, allows for delivery of liquid paclitaxel into whole bifurcation lesions without repeat stent implantation. After conventional percutaneous transluminal coronary angioplasty, local delivery of paclitaxel using two GENIE catheters in the kissing balloon technique was performed in three patients (left anterior descending, left circumflex and right coronary arteries) with highly symptomatic in-stent bifurcation stenoses. The intervention was feasible and safe in all coronary arteries. Final angiography and control angiography after six months showed good results. No major adverse cardiac events occurred 30 days and six months after intervention. The patients, who represent a group at high risk of recurrent instent restenosis, remained asymptomatic since the local drug delivery. They did not require insertion of a drug-eluting stent or crossover to coronary artery bypass surgery. In conclusion, this new treatment strategy proved to be safe and effective in this first human experience and offers a promising alternative to surgery or implantation of additional stents in these patients.

Local paclitaxel delivery after coronary stenting in an experimental animal model.

The goal of this study was to test the safety and efficacy of local paclitaxel delivery via a newly designed application catheter in an experimental animal study. Drug-eluting stents reduce restenosis in comparison to bare-metal stents. The drug-eluting polymer, however, may exert potential thrombogenic and inflammatory effects. A catheter-based local paclitaxel delivery offers further advantages, particularly a homogenous drug transfer into the vessel wall and a pharmacotherapy of the stent edges. In 30 pigs, both bare-metal stent (3.0 x 13 mm) implantation and balloon angioplasty were performed. Ten pigs received subsequent local delivery of paclitaxel-solution via a newly designed catheter (Genie, ACROSTAK corp., Switzerland), 10 animals served as a sham group and received vehicle (0.9% NaCl solution) and 10 animals were used as a control group. All animals were treated with aspirin and clopidogrel to prevent stent thrombosis. After final angiography the vessels were excised 42 days after intervention and prepared for histological and histomorphometric analysis. All coronary arteries showed complete endothelialization 42 days following treatment. Paclitaxel treatment led to a marked reduction of neointimal proliferation either post stent implantation (neointimal area: 1.04 +/- 0.10 mm(2) vs. 2.37 +/- 0.23 mm(2), p < 0.001) or post balloon dilatation (neontimal area: 0.35 +/- 0.14 mm(2), vs. 0.68 +/- 0.24 mm(2), p < 0.01). There were no significant angiographic or histomorphometric differences between the control and the sham group. In both paclitaxel groups neither angiographic edge phenomena nor a significant histomorphometric inflammatory response were found in the treated vessel segments. In conclusion, the local application of paclitaxel via the Genie catheter is safe and effective to significantly reduce the proliferative response post-stent implantation or balloon dilatation in an experimental animal model.

Local delivery of soluble platelet collagen receptor glycoprotein VI inhibits thrombus formation in vivo.

Platelet-mediated thrombus formation at the site of vascular injury is a major trigger for thrombo-ischemic complications after coronary interventions. The platelet collagen receptor glycoprotein VI (GPVI) plays a critical role in the initiation of arterial thrombus formation. Endothelial denudation of the right carotid artery in rabbits was induced through balloon injury. Subsequently, local delivery of soluble, dimeric fusion protein of GPVI (GPVI-Fc) (n = 7) or control Fc (n = 7) at the site of vascular injury was performed with a modified double-balloon drug-delivery catheter. Thrombus area within the injured carotid artery was quantified using a computer-assisted image analysis and was used as index of thrombus formation. The extent of thrombus formation was significantly reduced in GPVI-Fc- compared with control Fc-treated carotid arteries (relative thrombus area, GPVI-Fc vs. Fc: 9.3 +/- 4.2 vs. 2.3 +/- 1.7, p < 0.001). Local delivery of soluble GPVI resulted in reduced thrombus formation after catheter-induced vascular injury. These data suggest a selective pharmacological modulation of GPVI-collagen interactions to be important for controlling onset and progression of pathological arterial thrombosis, predominantly or even exclusively at sites of injured carotid arteries in the absence of systemic platelet therapy.

Usefulness of noninvasive MSCT coronary angiography as first-line imaging technique in patients with chest pain: initial clinical experience.

PURPOSE: Comparative studies with invasive coronary angiography (ICA) indicated a good sensitivity and specificity in the noninvasive detection of coronary artery disease (CAD) using Multi-slice spiral computed tomography coronary angiography (MS-CTA). The aim was to investigate the usefulness of MS-CTA as first-line imaging technique in patients (pts) with known or suspected CAD and low to intermediate probability of a severe coronary lesion. We report on our initial clinical experience using MS-CTA without compelled ICA. MATERIAL AND METHODS: One hundred thirty six patients with chest pain underwent MS-CTA on an outpatient basis (age 60+/-10, suspicion of CAD: n=95, suspicion of restenosis: n=24, after CABG: n=17). Based on the MS-CTA results, a recommendation concerning further diagnostics and therapy was given to each pt. A telephone interview was performed after 455+/-166 days to evaluate the further clinical course. RESULTS: Per pt, 8.2+/-2.7 coronary segments could be evaluated. Based on the MSCT results, the presence of flow-limiting stenoses was excluded in n=77 (57%) pts (group I). An additional ICA was recommended in n=59 (43%) pts (group II). An ICA had been performed in meantime in 27/136 (20%) pts, and could be avoided in the majority of pts. Nevertheless, 58/136 (42%) pts reported on improved clinical symptoms and 42/136 (31%) pts of improved quality of life. CONCLUSIONS: MS-CTA was found to be useful to evaluate the need and to reduce the total number of ICA in pts with unclear chest pain. It appears to be the first noninvasive modality, which might be used on a clinical routine basis in selected groups of pts.

Stent-based delivery of tissue inhibitor of metalloproteinase-3 adenovirus inhibits neointimal formation in porcine coronary arteries.

BACKGROUND: Stent-based antiproliferative therapy appears to decrease in-stent restenosis. However, alternative approaches might produce equivalent efficacy with better long-term safety. In previous work, an adenovirus capable of expressing the tissue inhibitor of metalloproteinase-3 (RAdTIMP-3) inhibited neointima formation in cell cultures and porcine saphenous vein grafts. RAdTIMP-3 decreased smooth muscle cell migration, stabilized the extracellular matrix, and uniquely promoted apoptosis. The current study developed eluting stent technology to deliver RAdTIMP-3 during stenting of pig coronary arteries. METHODS AND RESULTS: Binding of virus to and elution from stents and transduction of pig coronary arteries were confirmed using beta-galactosidase as a reporter gene in vitro and in vivo. Deployment of RAdTIMP-3-coated stents increased apoptosis and reduced neointimal cell density, but did not increase inflammation or proliferation compared with beta-galactosidase-expressing adenovirus (RAdlacZ). Neointimal area after 28 days was significantly reduced to 1.27+/-0.19 mm2 with RAdTIMP-3 versus 2.61+/-0.31 mm2 with RAdlacZ stents (P<0.001) and 2.12+/-0.20 mm2 with bare stents (P<0.005). CONCLUSIONS: Our results demonstrate for the first time to our knowledge the feasibility of adenovirus-coated stent technology and highlight the potential of TIMP-3 to produce significant inhibition of in-stent neointima formation.