Biomedical subjects

Robert L Wilensky

Publications and source records attributed to Robert L Wilensky.

At least 19 recordsLinked to original sources

PubMed2007

Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution.

We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.

Asian People↗

PubMed2006

Effect of gender on prognosis following percutaneous coronary intervention for stable angina pectoris and acute coronary syndromes.

Women with non-ST-elevation acute coronary syndromes (NSTACSs) may have better outcomes than men, but the effect of NSTACSs in women undergoing percutaneous coronary intervention (PCI) has not been examined. We performed a prospective, multicenter, cohort study of consecutive patients who underwent PCI for NSTACS and stable angina during 3 National Heart, Lung, and Blood Institute Dynamic Registry recruitment waves (1997 to 2002) to examine the effect of female gender on adverse clinical events after PCI or stable angina for NSTACS. The primary end point was the combined rate of death, myocardial infarction, or rehospitalization for cardiac causes at 1 year. Compared with men with NSTACS (n = 2,124), women (n = 1,338) were older and more often had hypertension, diabetes mellitus, and history of heart failure (p <0.001 for all), whereas multivessel disease was less frequent (p <0.01). Procedural success and in-hospital adverse event rates were similar. Women with NSTACS had the highest 1-year rate of death/myocardial infarction/cardiac rehospitalization compared with women with stable angina pectoris (n = 462) or men (n = 995; women with NSTACS 37.6%, men with NSTACS 29.8%, women with stable angina 29.4%, men with stable angina 27.7%, p <0.001). The higher rate remained after adjustment for differences in baseline characteristics (adjusted hazard ratio 1.37, 95% confidence interval 1.20 to 1.56). Among women, NSTACS conferred a significantly higher risk for adverse events compared with stable angina (adjusted hazard ratio 1.41, p = 0.001), whereas the risk of adverse events was not different in men (adjusted hazard ratio 1.05, p = 0.5). In conclusion, women undergoing PCI for NSTACS have a higher risk of major adverse cardiac events than men or women undergoing PCI for stable angina.

Aged↗

PubMed2006

Comparison of the efficacy of direct coronary stenting with sirolimus-eluting stents versus stenting with predilation by intravascular ultrasound imaging (from the DIRECT trial).

A direct coronary stenting technique using drug-eluting stents may decrease drug-eluting stent efficacy due to possible damage to the surface coating of the stent. The DIRECT is a multicenter, prospective, nonrandomized trial designed to evaluate the direct stenting strategy for the sirolimus-eluting Bx-Velocity stent compared with the historical control (SIRIUS trial, stenting with predilation). Volumetric and cross-sectional intravascular ultrasound analyses at 8-month follow-up were performed in 115 patients (DIRECT n= 64, control n = 51). Patient and lesion characteristics were comparable between groups. The DIRECT group achieved an equivalent uniform expansion index, defined as minimum stent area/maximum stent area x 100, compared with the control group (65.9 +/- 11.7 vs 63.1 +/- 12.7, p = NS). At 8-month follow-up, vessel, stent, lumen, and neointimal volume index (volume in cubic millimeters/length in millimeters) and percent neointimal volume were similar between the DIRECT and control groups (vessel volume index 13.9 +/- 4.40 vs 15.0 +/- 3.83; stent volume index 6.83 +/- 2.02 vs 6.94 +/- 2.04; lumen volume index 6.71 +/- 2.04 vs 6.81 +/- 2.07; neointimal volume index 0.14 +/- 0.24 vs 0.16 +/- 0.23; percent neointimal volume 3.73 +/- 6.97 vs 3.14 +/- 5.32, p = NS for all). In addition, in-stent neointimal hyperplasia distribution was significantly smaller near the distal stent edge (0.22 vs 0.098 mm(3)/mm, p = 0.01 for an average neointimal volume index within 3 mm from the distal stent edge). In conclusion, direct coronary stenting with the sirolimus-eluting Bx-Velocity stent is equally effective in terms of uniform stent expansion and long-term quantitative intravascular ultrasound results compared with conventional stenting using predilation. This strategy appears to be associated with less neointimal hyperplasia near the distal stent edge.

Coronary Stenosis↗

PubMed2006

Outcome of percutaneous coronary intervention in unstable angina pectoris versus stable angina pectoris in two different time periods.

Percutaneous coronary intervention (PCI) for unstable angina pectoris (UAP) has traditionally been associated with a higher risk of ischemic complications than that for stable angina pectoris (SAP). However, PCI procedures have evolved, so this study was designed to determine whether PCI for UAP is still associated with less favorable outcomes. In-hospital and 1-year outcomes in Dynamic Registry patients who presented for PCI with UAP (n = 2,994) or SAP (n = 1,457) between 1997 and 2002 were compared. One-year results were also compared with consecutive patients who underwent angioplasty (n = 2,431) from the 1985 to 1986 Percutaneous Transluminal Coronary Angioplasty Registry. Although Dynamic Registry patients with UAP were older and more likely to smoke (p < 0.05), have diabetes mellitus (p = 0.03), or a previous myocardial infarction (p < 0.001), procedural success was higher than in patients with SAP. By 1 year, there was greater risk of death (4.4% vs 2.6%, p < 0.01), death/myocardial infarction (9.9% vs 6.6%, p < 0.001), and death, myocardial infarction, and coronary artery bypass grafting (15.1% vs 11.6%, p < 0.01) in patients with UAP. In patients with UAP, there was no significant difference in adjusted 1-year death and death/myocardial infarction rates when comparing the waves of the Dynamic Registry with those of the Percutaneous Transluminal Coronary Angioplasty Registry, although death/myocardial infarction rates among Dynamic Registry patients were lower. However, in patients with SAP, the adjusted rate for death/myocardial infarction was lower in wave 3, and for death, myocardial infarction, and revascularization, there was a significant decrease in event rates with each successive recruitment period (p < 0.05 for all comparisons). In conclusion, in contradistinction to patients with SAP, death and death/myocardial infarction rates in patients who have undergone PCI for UAP have not significantly decreased over the past 16 years and patients with UAP remain at a greater risk of ischemic events at 1 year compared with patients with SAP.

Angina, Unstable↗

PubMed2006

Role of lipoprotein-associated phospholipase A2 in leukocyte activation and inflammatory responses.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an emerging cardiovascular risk marker. To explore the biologic role of Lp-PLA2 in atherosclerosis, we examined its expression and contribution to leukocyte activation under proatherogenic conditions. METHODS AND RESULTS: Following the induction of diabetes and hypercholesterolemia in a porcine model, a rapid increase in plasma Lp-PLA2 activity was observed at 1 month. This was accompanied by upregulated Lp-PLA2 mRNA expression by peripheral blood mononuclear cells (PBMC) at 3 months, and elevated Lp-PLA2 mRNA expression in coronary arteries at 6 months. These changes were paralleled by increased inflammatory responses by circulating PBMC (ICAM-1, IL-6), in coronary tissues (ICAM-1, VCAM-1), and the subsequent accumulation of inflammatory cells. In human PBMC, proinflammatory mediators augmented the synthesis and release of functional Lp-PLA2. Furthermore, lysophosphatidylcholine (lysoPC), a product of Lp-PLA2 activity, induced an increase in several inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in a concentration-dependent manner. In contrast, Lp-PLA2 inhibition (SB677116; 1 microM) abrogated the inflammatory response elicited by oxidized LDL. CONCLUSIONS: In an experimental model of diabetes and hypercholesterolemia, leukocyte activation was associated with augmented Lp-PLA2 expression. In vitro, Lp-PLA2 activity mediated leukocyte activation and inflammatory responses, whereas Lp-PLA2 inhibition abolished inflammatory responses induced by oxidized LDL. Collectively, these observations support a proatherogenic role for Lp-PLA2.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2006

Rash with both clopidogrel and ticlopidine in two patients following percutaneous coronary intervention with drug-eluting stents.

OBJECTIVE: To describe 2 cases of rash that occurred following oral administration of both clopidogrel and ticlopidine and to review previously published case reports. CASE SUMMARY: Two patients developed maculopapular pruritic rashes that began on the abdomen and spread to the back, neck, and face following clopidogrel administration after placement of a drug-eluting intracoronary stent. Following recurrence of the rash after ticlopidine was initiated, thienopyridines were discontinued, and the patients were treated for 3-6 months with aspirin, cilostazol, and enoxaparin or warfarin for prevention of stent thrombosis and reinfarction. One patient self-discontinued cilostazol, reinitiated clopidogrel, and redeveloped a rash. DISCUSSION: While there have been several published cases of thienopyridine-associated rash, there have been only 2 reported cases of cross-sensitivity between orally administered clopidogrel and ticlopidine. Preliminary reports suggest that clopidogrel desensitization may be accomplished in selected patients several months to years following thienopyridine rash using an allergy desensitization protocol, with close monitoring for anaphylaxis. An objective causality assessment using the Naranjo probability scale indicated that both ticlopidine and clopidogrel were probable causes of the rash in the first patient; in the second patient, clopidogrel was judged a definite cause and ticlopidine was a probable cause of the rash. CONCLUSIONS: In a patient who develops a rash following clopidogrel treatment after intracoronary stent placement, ticlopidine therapy should be attempted, provided the initial reaction did not include life-threatening symptoms. In a patient who experiences rash with both clopidogrel and ticlopidine and does not have a contraindication to cilostazol or anticoagulation, therapy with aspirin, cilostazol, and either enoxaparin or warfarin may be administered for 2-6 months following placement of a drug-eluting stent.

Angioplasty, Balloon, Coronary↗

PubMed2006

Role of magnetic resonance and intravascular magnetic resonance in the detection of vulnerable plaques.

Noninvasive magnetic resonance imaging (MRI) has been used to determine vascular three-dimensional structure, detect the presence of subclinical atherosclerotic disease in high-risk patient subgroups, and optimize and follow therapy in individual patients. The outstanding soft-tissue-characterizing capabilities of MRI permit depiction of various components of atherothrombotic plaque, including lipid, fibrous tissue, calcium, and thrombus formation. However, noninvasive MRI visualization of coronary arteries is currently limited by the small size of the coronary arteries, the deep arterial location, and arterial motion. The combination of MR imaging and molecular probes offers exciting possibilities of direct visualization of biologic processes within atherosclerotic tissue. The self-contained intravascular MRI probe appears to hold promise in the identification of high-risk coronary atherosclerotic lesions with increased superficial lipid content.

Animals↗

PubMed2006

Hypercholesterolemia suppresses inwardly rectifying K+ channels in aortic endothelium in vitro and in vivo.

Inwardly rectifying K+ (Kir) channels are responsible for maintaining endothelial membrane potential and play a key role in endothelium-dependent vasorelaxation. In this study, we show that endothelial Kir channels are suppressed by hypercholesterolemic levels of lipoproteins in vitro and by serum hypercholesterolemia in vivo. Specifically, exposing human aortic endothelial cells to acetylated low-density lipoprotein or very low density lipoprotein resulted in a time- and concentration-dependent decrease in Kir current that correlated with the degree of cholesterol loading. The suppression was fully reversible by cholesterol depletion. Furthermore, a decrease in Kir current resulted in depolarization of endothelial membrane potential. Most important, the flow sensitivity of Kir currents was also impaired by cholesterol loading. Specifically, flow-induced increase in Kir current was suppressed by 70%, and flow-induced hyperpolarization was almost completely abrogated. Furthermore, we show that hypercholesterolemia in vivo also strongly suppresses endothelial Kir currents and causes a shift in endothelial membrane potential, as determined by comparing the currents in aortic endothelial cells freshly isolated from healthy or hypercholesterolemic pigs. Therefore, we suggest that suppression of Kir current is one of the important factors in hypercholesterolemia-induced endothelial dysfunction.

Animals↗

PubMed2006

A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction.

AIMS: Mesenchymal stem cells (MSCs), rare bone marrow-derived stem cell precursors of non-haematopoietic tissues, have shown promise in potentially repairing infarcted myocardium. These and similar cell types are being tested clinically, but understanding of delivery and subsequent biodistribution is lacking. This study was designed to quantitatively compare MSC engraftment rates after intravenous (IV), intracoronary (IC), or endocardial (EC) delivery in a porcine myocardial infarction (MI) model. METHODS AND RESULTS: Allogeneic, male MSCs were cultured from porcine bone marrow aspirates. Iridium nanoparticles were added during culturing and internalized by the MSCs. An MI was induced in female swine (27-40 kg in size) by prolonged balloon occlusion of the mid-left anterior descending artery. Animals (n = 6 per group) were randomized to one of three delivery methods. Cellular engraftment was determined 14+/-3 days post-delivery by measuring ex-vivo the iridium nanoparticle concentration in the infarct. Confirmation of cellular engraftment utilized both DiI and fluorescence in situ hybridization (FISH) labelling techniques. During MSC infusion, no adverse events were noted. However, following IC infusion, half of the pigs exhibited decreased blood flow distal to the infusion site. At 14 days, the mean number of engrafted cells within the infarct zone was significantly greater (P< or =0.01) following IC infusion than either EC injection or IV infusion and EC engraftment was greater than IV engraftment (P< or =0.01). There was less systemic delivery to the lungs following [EC vs. IV (P = 0.02), EC vs. IC (P = 0.06)]. Both DiI and FISH labelling demonstrated the presence of engrafted male MSCs within the female infarcted tissue. CONCLUSION: IC and EC injection of MSCs post-MI resulted in increased engraftment within infarcted tissue when compared with IV infusion, and IC was more efficient than EC. However, IC delivery was also associated with a higher incidence of decreased coronary blood flow. EC delivery into acutely infarcted myocardial tissue was safe and well tolerated and was associated with decreased remote organ engraftment with compared with IC and IV deliveries.

Animals↗

PubMed2006

Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.

We have previously reported suggestive linkage of type 2 diabetes mellitus to chromosome 10q. We genotyped 228 microsatellite markers in Icelandic individuals with type 2 diabetes and controls throughout a 10.5-Mb interval on 10q. A microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with type 2 diabetes (P = 2.1 x 10(-9)). This was replicated in a Danish cohort (P = 4.8 x 10(-3)) and in a US cohort (P = 3.3 x 10(-9)). Compared with non-carriers, heterozygous and homozygous carriers of the at-risk alleles (38% and 7% of the population, respectively) have relative risks of 1.45 and 2.41. This corresponds to a population attributable risk of 21%. The TCF7L2 gene product is a high mobility group box-containing transcription factor previously implicated in blood glucose homeostasis. It is thought to act through regulation of proglucagon gene expression in enteroendocrine cells via the Wnt signaling pathway.

Chromosome Mapping↗

PubMed2006

The impact of ejection fraction on outcomes after percutaneous coronary intervention in patients with congestive heart failure: an analysis of the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry and Dynamic Registry.

BACKGROUND: Patients with congestive heart failure (CHF) have higher rates of adverse outcomes after percutaneous coronary intervention (PCI). A comprehensive analysis of outcomes in patients with CHF in the current era has not been done. We studied the outcomes of patients with CHF who underwent PCI in the National Heart, Lung, and Blood Institute-sponsored Percutaneous Transluminal Coronary Angioplasty (PTCA) and Dynamic registries. METHODS: We evaluated demographic and angiographic characteristics and the clinical outcomes of patients with CHF in the Dynamic Registry and the PTCA Registry, excluding patients with acute myocardial infarction. In the Dynamic Registry, patients with CHF (n = 503) were compared with patients without CHF (n = 4194), and patients with CHF with a preserved ejection fraction (EF) (n = 134) were compared with patients with CHF who have a reduced EF (n = 199). The patients with CHF in the 1997 through 2001 Dynamic Registry (n = 236) were then similarly compared with patients with CHF in the earlier PTCA Registry (n = 117). RESULTS: In the Dynamic Registry, compared with patients without CHF, patients with CHF had a higher-risk clinical and angiographic profile, and a higher mortality rate both inhospital (2.6% vs 0.4%, P < or = .001) and at 1 year (13.1% vs 3.0%, P < .001). Patients with reduced EF had higher inhospital mortality rates and a trend toward higher mortality at 1 year. The patients with CHF in the Dynamic Registry compared with those in the PTCA Registry had a higher risk profile yet had significantly higher procedural success rates and improved clinical outcomes. CONCLUSIONS: Although CHF remains a strong predictor of adverse outcomes after PCI, significant improvement seen in the past decade is likely related to improved procedural techniques and improved medical therapy.

Aged↗

PubMed2005

Bisphosphonate-mediated gene vector delivery from the metal surfaces of stents.

The clinical use of metallic expandable intravascular stents has resulted in improved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-bisphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine bisphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular bisphosphonate layer on metal alloy surfaces (steel, nitinol, and cobalt-chromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Ad-inducible nitric oxide synthase (iNOS) attached to the bisphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ratio 1.68 +/- 0.27 and 3.4 +/- 0.35; Ad-iNOS vs. control, P < 0.01). It is concluded that effective gene vector delivery from metallic stent surfaces can be achieved by using this approach.

Adenoviridae↗

PubMed2005

Site specific gene delivery in the cardiovascular system.

Gene therapy holds great promise for treating both genetic and acquired disorders. However, progress toward effective human gene therapy has been thwarted by a number of problems including vector toxicity, poor targeting of diseased tissues, and host immune and inflammatory activity to name but a few of the challenges. Gene therapy for cardiovascular disease has been the subject of many fewer clinical trials than other disorders such as cancer or cystic fibrosis. Nevertheless, the challenges are comparable. The present paper reports a review of investigations related to our hypothesis that site specific cardiovascular gene therapy represents an approach that can lead to both optimizing efficacy and reducing the impact of gene vector-related systemic adverse effects. We report experimental studies demonstrating proof of principle in three areas: gene therapy for heart valve disease, gene delivery stents, and gene therapy to treat cardiac arrhythmias. Heart valve disease is the second most common indication for open heart surgery and is now only treatable by surgical removal or repair of the diseased heart valve. Our investigations demonstrate that gene vectors can be immobilized on the surface of prosthetic heart valve leaflets thereby enabling a therapeutic genetic modification of host cells around the valve annulus and on the leaflet. Other animal studies have shown that vascular stents used to relieve arterial obstruction can also be used as gene delivery systems to provide therapeutic vector constructs that can both locally prevent post stenting reobstruction, known as in-stent restenosis, and treat the underlying vascular disease. Cardiac arrhythmias are the cause of sudden death due to heart disease and affect millions of others on a chronic basis. Our group has successfully investigated in animal studies localized gene therapy using an ion channel mutation to treat atrial arrhythmias.

Animals↗

PubMed2005

Diagnosis of thin-cap fibroatheromas by a self-contained intravascular magnetic resonance imaging probe in ex vivo human aortas and in situ coronary arteries.

OBJECTIVES: We sought to correlate findings obtained from a self-contained magnetic resonance imaging (MRI) probe with plaque morphology of ex vivo human aortas and coronary arteries. BACKGROUND: Early detection of thin-cap fibroatheromas (TCFAs) may allow for early preventive treatment of acute coronary syndromes. We developed an intravascular MRI catheter capable of imaging the arterial wall without external magnets or coils by differentiating lipid-rich and fibrotic-rich areas of the atherosclerotic plaque on the basis of differential water diffusion. METHODS: Aortic samples (n = 16) and coronary arteries were obtained within 12 h of death. Coronary specimens were intermediate in angiographic severity (30% to 60% luminal narrowing, n = 18). Blinded histologic and immunohistochemical analyses of the tissues were performed and correlated to MRI findings. RESULTS: The 16 aortic lesions included four ulcerated plaques, two TCFAs, two thick-cap fibrous atheromas, two intimal xanthomas, and six adaptive intimal thickenings. The MRI scan correctly correlated with the histologic diagnosis in 15 (94%) of 16 lesions. The 18 coronary lesions included one plaque rupture, three TFCAs, seven thick-cap fibrous atheromas, four fibrocalcific plaques, two intimal xanthomas, and one adaptive intimal thickening. The MRI scan correlated with the histologic diagnosis in 16 of 18 lesions (sensitivity 100%, specificity 89%). CONCLUSIONS: The self-contained intravascular MRI catheter successfully identified TCFA and may prove to be an important diagnostic approach to determining the presence of lesions with increased risk of causing death or myocardial infarction.

Aorta↗

PubMed2005

Importance of the postdischarge interval in assessing major adverse clinical event rates following percutaneous coronary intervention.

In-hospital major adverse clinical event (MACE) rates after percutaneous coronary intervention serve as benchmarks of performance. However, accelerated clinical pathways, decreased lengths of stay, and potential delayed effects of percutaneous coronary intervention may result in an underestimation of this traditional measurement of outcome. Records from patients in the first 3 waves of the National Heart, Lung, and Blood Institute's Dynamic Registry (n = 6,676) were reviewed for rates of composite in-hospital MACEs (death, myocardial infarction, and any repeat target vessel revascularization) and postdischarge MACEs (death, myocardial infarction, repeat hospitalization, and repeat target vessel revascularization) through 30 days. Rates for each composite MACE were compared across waves to assess changes over time. Predictors of each MACE category were identified using multivariate analysis. In-hospital MACE decreased significantly (5.4% of wave 1, 4.9% of wave 2, 3.1% of wave 3, p <0.001), whereas stent implantation increased significantly (67.5% of wave 1, 79.1% of wave 2, 86.2% of wave 3, p <0.001). Postdischarge MACE through 30 days remained unchanged (5.1% of wave 1, 5.1% of wave 2, 4.8% of wave 3, p = 0.6). Mean length of stay decreased (2.7 days for wave 1, 2.2 days for wave 3, p <0.001). Disparate clinical, procedural, and angiographic factors were associated with each MACE. Postdischarge MACE rates through 30 days comprise a significant and unchanging fraction of overall procedurally related MACE rates despite improving in-hospital outcomes. Most postdischarge events derive from pathology related to the controlled vessel. A 30-day MACE rate may serve as a more comprehensive measurement of procedural outcome.

Aged↗

PubMed2005

Usefulness of noncoronary vascular disease in predicting adverse events in the year following percutaneous coronary intervention.

It is unknown whether noncoronary vascular disease is associated with persistent cardiac risk in patients who undergo percutaneous coronary intervention (PCI). Using the National Heart, Lung, and Blood Institute Dynamic Registry, the incidence of death, myocardial infarction (MI), and repeat revascularization outcomes were compared in patients who had noncoronary vascular disease (n = 554) with patients who did not (n = 4,075). Vascular disease was defined as a history of stroke, transient ischemic attack, claudication, vascular bypass, limb amputation, or aortic aneurysm. Patients who had concomitant noncoronary vascular disease had more significant co-morbidities. Angiographic success rate was lower in patients who had concomitant noncoronary vascular disease (89.5% vs 93.2%, p <0.01), whereas in-hospital adverse events, including death (2.7% vs 1.3%, p <0.05), MI (4.7% vs 2.6%, p <0.01), stroke (1.1% vs 0.2%, p <0.001), major entry site complication (6.7% vs 3.5%, p <0.001), and need for coronary artery bypass grafting (2.2% vs 1.1%, p <0.05) were significantly higher. One-year death rate (10.5% vs 4.5%, p <0.001) and MI rate (9.2% vs 5.2%, p <0.001) were also significantly higher in patients who had vascular disease. After adjustment, vascular disease was independently associated with a higher risk of death or MI (risk ratio 1.4, 95% confidence interval 1.1 to 1.8) and death, MI, or coronary artery bypass grafting (risk ratio 1.3, 95% confidence interval 1.1 to 1.6) at 1 year. Repeat PCI rates were similar (15.9% vs 13.8%, p = NS). In conclusion, the presence of noncoronary vascular disease is an independent predictor of MI and death or MI 1 year after PCI. Because PCI is often performed before vascular surgery, these data may lend insight to the risk/benefit ratio of such an approach.

Aged↗

PubMed2005

FilterWire distal embolic protection device for vein graft stenting: initial single-center experience.

BACKGROUND: Saphenous vein graft (SVG) intervention is associated with a significant incidence of major adverse cardiac events (MACE) related to distal vessel embolization. The FilterWire distal embolic protection device has recently been approved as an adjunct to SVG intervention. We report here our initial experience in a single center in 30 consecutive patients using this device in SVG stenting. HYPOTHESIS: This study examined the outcomes and complications associated with these devices, as well as whether proficiency with the devices increased with greater experience and whether there were measurable outcome differences between devices. METHODS: We retrospectively identified all patients in whom a FilterWire device was placed at our hospital between June 2001 and June 2004. RESULTS: The device was successfully deployed in 29 of 30 patients, and all patients were stented successfully. Overall MACE rate was 6.6%, consistent with reports in larger multicenter clinical trials. Transient decreases in flow were noted while the device was in place in six patients, but improved in five patients with device removal. CONCLUSIONS: This early experience in a single center using FilterWire embolic protection indicates that excellent clinical results can be obtained by the adoption of filter protection for SVG intervention, without evidence for a detrimental learning curve.

Aged↗

PubMed2005

Temporal variation in inhospital mortality with percutaneous coronary intervention: a report from the National Heart, Lung and Blood Institute Dynamic Registry.

BACKGROUND: Cardiovascular morbidity and mortality display a distinct time dependence also known as circadian variation. Whether such time dependence extends to the risk of procedural-related mortality after percutaneous coronary intervention (PCI) is presently unknown. METHODS: Inhospital mortality was analyzed in 6,347 patients with PCI start times from 8:00 am to 6:59 pm ("usual" workday). The sample was divided into 3 evenly populated groups (morning start 8:00-10:59 AM, midday start 11:00 AM-1:59 PM, afternoon start 2:00-6:59 PM). The association between procedural start time and mortality was assessed using multivariable analysis including a propensity score accounting for factors associated with procedural start time. RESULTS: There was a significant, nonlinear relationship between procedural-related mortality and start time (P = .03). Afternoon start patients were at higher adjusted risk of mortality compared with midday start patients (OR 2.03, 95% CI 1.07-3.83, P = .03 ). Morning start patients were also at higher risk compared with midday start patients although the association was not statistically significant (OR 1.73, 95% CI 0.89-3.39, P = .11). CONCLUSIONS: There is a significant time-dependent variation in the risk of inhospital PCI-related mortality during usual working hours. The highest risk period, taking into account numerous factors that confound this association, is the latter part of the workday. A second period of apparent greater risk occurs during the early part of the workday and is consistent with our present understanding of circadian variation in cardiovascular disease processes.

Aged↗