A gender-specific analysis of association between hyperuricaemia and cardiovascular events in patients with coronary artery disease.

BACKGROUND AND AIMS: Gender-related differences in the association between hyperuricaemia and cardiovascular events remain poorly understood. The objective of this study was to assess gender-related differences in the association between hyperuricaemia and cardiovascular events in patients with coronary artery disease (CAD). METHODS AND RESULTS: This study included 13,273 patients with CAD. Hyperuricaemia was defined as a plasma uric acid >7.0mgdl(-1) in men and >5.7mgdl(-1) in women. The primary outcome was 1-year all-cause mortality. Hyperuricaemia was found in 3745 men (36.5%) and 1562 women (50.3%); odds ratio (OR)=1.76, 95% confidence interval (CI) 1.62-1.91; P<0.001. Women with hyperuricaemia were older, had higher proportions of patients with diabetes and arterial hypertension and had reduced renal function and higher C-reactive protein levels compared with men with hyperuricaemia. One-year all-cause mortality was 9.3% (n=143) in women with hyperuricaemia versus 6.9% (n = 252) in men with hyperuricaemia (P=0.002). After adjustment in multivariable Cox proportional hazards model, uric acid predicted 1-year mortality with an adjusted hazard ratio (HR)=1.17, 95% CI (1.03-1.31), P=0.012 in men and HR=1.25, 95% CI (1.06-1.48), P=0.007 in women, for each standard deviation increase in the natural logarithm. Uric acid predicted 1-year mortality with an area under the receiver-operating characteristic curve=0.625, 95% CI (0.594-0.656) in men and 0.676, 95% CI (0.635-0.717) in women (P=0.044, for women versus men). CONCLUSION: Hyperuricaemia predicts an increased risk of 1-year mortality in both genders with a stronger association in women. Differences in cardiovascular risk profile may explain the stronger association between hyperuricaemia and cardiovascular events in women.

P27 and P53 gene polymorphisms and restenosis following coronary implantation of drug-eluting stents.

OBJECTIVE: Drug-eluting stents (DES) have reduced restenosis rates compared with bare-metal stents. P27 and P53 play important roles in the signal transduction leading to neointimal growth inhibition and induction of apoptosis of smooth muscle cells due to rapamycin and paclitaxel. We hypothesized that genetic variants of P27 and P53 influence the development of restenosis and the clinical outcome of patients receiving DES. METHODS: Polymorphisms in the genes encoding for P27 and P53 were tested for their association with restenosis and major adverse cardiac events. P27 C-79T and P53 G72C polymorphism genotypes were determined in a series of 433 consecutive patients receiving DES. Follow-up angiography after 6 months was performed in 87% of the patients. Genotyping was performed with PCR-based methods. RESULTS: For patients with the respective P27 C-79T and P53 G72C genotypes, the angiographic restenosis rates were between 5.0 and 22.0%, and the clinical restenosis rates were between 0.0 and 16.3%, without significant differences for the studied genotypes (p > 0.19). There was no association of the studied genotypes with the 1-year incidences of death and myocardial infarction. CONCLUSION: This study could not demonstrate a clinically relevant role of P27 and P53 polymorphisms in the processes leading to in-stent restenosis.

Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation.

OBJECTIVES: Optimal antithrombotic/anticoagulation therapy in patients on chronic oral anticoagulation (OAC) undergoing drug-eluting stent (DES) implantation is unknown. We investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC. METHODS: We included a series of 515 patients on OAC who underwent DES implantation between 2002 and 2007. Based on predefined clinical and echocardiographic criteria, 306 patients continued OAC (triple therapy) and 209 patients discontinued OAC (dual therapy) for the time they received antiplatelet therapy with clopidogrel and aspirin [stent-related antithrombotic treatment (SRAT)]. The primary end point was a composite of death, myocardial infarction, stent thrombosis or stroke. RESULTS: During SRAT the primary endpoint was observed in 13 patients in the group with triple therapy versus 15 patients in the group with dual therapy [Kaplan-Meier estimates 4.2% and 7.2%, odds ratio (OR) = 0.61, 95% confidence interval (CI) 0.29-1.28; P = 0.19]. At 2 years of follow-up, the primary endpoint was observed in 35 patients in the group with triple therapy versus 36 patients in the group with dual therapy (Kaplan-Meier estimates 14.1% and 18.0%, OR = 0.76, 95% CI: 0.48-1.21; P = 0.25). Two-year incidence of major bleeding was 1.4% (n = 4, triple therapy) versus 3.1% (n = 6, dual therapy) (P = 0.34). CONCLUSIONS: In patients on chronic OAC undergoing DES implantation, clinical and echocardiographic criteria help to define postprocedural antithrombotic/anticoagulation therapy. Based on these criteria, both a double antiplatelet therapy (clopidogrel plus aspirin) and a triple therapy (OAC plus clopidogrel plus aspirin) are associated with favourable safety and efficacy.

Myeloperoxidase level in patients with stable coronary artery disease and acute coronary syndromes.

BACKGROUND: No studies have measured plasma myeloperoxidase (MPO) across the entire spectrum of patients with coronary artery disease (CAD). The aim of the study was to compare MPO level across the entire spectrum of CAD, to assess the accuracy of MPO in predicting acute coronary syndromes and to define independent correlates of MPO level. DESIGN: This case-control study included 874 patients with angiographically proven CAD. Cases included 680 patients with CAD (382 patients with stable CAD, 107 patients with non-ST-segment elevation acute coronary syndromes and 191 patients with ST-segment elevation acute myocardial infarction). Controls included 194 subjects with normal coronary angiograms. MPO was measured using an enzyme immunoassay before angiography and heparin administration. RESULTS: MPO level [median (25th-75th percentiles)] was 74.5 (52.5-135.3) microg L(-1) in cases vs. 61.2 (44.6-80.9), microg L(-1) in controls (P < 0.001). MPO level was 61.2 (47.5-85.8), microg L(-1) in patients with stable CAD, 99.2 (62.2-154.9), microg L(-1) in patients with non-ST-segment elevation acute coronary syndromes and 129.5 (72.2-216.0) microg L(-1) in patients with acute myocardial infarction (P < 0.001). Elevated MPO level was associated with acute coronary syndromes with an area under receiver operating characteristic (ROC) curve of 0.731 (95% confidence interval 0.692-0.770; P < 0.001). Independent correlates of MPO level were acute coronary syndrome (P < 0.001), high-sensitivity C-reactive protein (P = 0.007), creatinine (P = 0.026), left ventricular ejection fraction (P = 0.027, negative association) and smoking (P = 0.028). CONCLUSIONS: MPO level is elevated in patients with CAD and higher levels of MPO were found with progression of CAD from stable CAD to non-ST-segment elevation acute coronary syndromes and to acute myocardial infarction.

Gene transfer of heterologous G protein-coupled receptors to cardiomyocytes: differential effects on contractility.

In heart failure, reduced cardiac contractility is accompanied by blunted cAMP responses to beta-adrenergic stimulation. Parathyroid hormone (PTH)-related peptide and arginine vasopressin are released from the myocardium in response to increased wall stress but do not stimulate contractility or adenylyl cyclase at physiological concentrations. To bypass the defective beta-adrenergic signaling cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V(2) vasopressin receptors (rV(2)-Rs), which are normally not expressed in the myocardium and which are both strongly coupled to adenylyl cyclase, and recombinant beta(2)-adrenergic receptors (rbeta(2)-ARs) were overexpressed in cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to increase contractility via the heterologous, recombinant receptors was compared. Whereas V(2)-Rs are uniquely coupled to Gs, PTH1-Rs and beta(2)-ARs are also coupled to other G proteins. Gene transfer of rPTH1-Rs or rbeta(2)-ARs to adult cardiomyocytes resulted in maximally increased basal contractility, which could not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs induced increased cAMP formation and phospholipase C activity. In contrast, healthy or failing rV(2)-R-expressing cardiomyocytes showed unaltered basal contractility. Their contractility and cAMP formation increased only at agonist exposure, which did not activate phospholipase C. In summary, we found that gene transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the transgene, as does that of beta(2)-ARS: In the absence of receptor agonists, rPTH1-Rs and rbeta(2)-ARs increase basal contractility, coupling to 2 G proteins simultaneously. In contrast, rV(2)-Rs are uniquely coupled to Gs and are not constitutively active, retaining their property to be activated exclusively on agonist stimulation. Therefore, gene transfer of V(2)-Rs might be more suited to test the effects of cAMP-stimulating receptors in heart failure than that of PTH1-Rs or beta(2)-ARS:

Clinical evidence on polymer-based sirolimus and paclitaxel eluting stents.

Percutaneous coronary interventions with the use of stents have become the mainstay treatment of patients with various clinical manifestations of coronary artery disease. Despite their remarkable success, restenosis has remained the major drawback and its prevention has absorbed intensive experimental and clinical research work. After the failure of multiple efforts with systemic use of various drugs, local application of antiproliferative and anti-inflammatory agents released by specially designed coated stents led to considerable suppression of neointima and opened new prospects in the prevention of restenosis. An increasing body of evidence is showing the advantages provided by drug-eluting stents (DES) in almost all subsets of patients with coronary artery disease with a drastic decrease in the need for reintervention. To date, the most commonly used and the only US Food and Drug Administration (FDA) approved DES are a sirolimus-eluting stent (Cypher) and a paclitaxel-eluting stent (Taxus), both of which are polymer-based DES and will constitute the focus of this review. Recent data demonstrate that DES are not equal in their safety and efficacy. A less optimistic aspect of DES technology are the reiterated concerns about a more prolonged risk of stent thrombosis. Although all agree on the need of a longer duration of dual antiplatelet therapy in patients treated with DES, its optimal length is still to be defined. Because polymers used for stent coating are often seen at the origin of the compromised long-term safety of DES, new technologies able to avoid permanent polymers may offer a valuable alternative.

Current drug-eluting stents in complex patients and lesions.

Drug-eluting stents (DES) are playing an increasingly important role in the treatment of coronary artery disease. These new devices work by releasing controlled amounts of pharmacological agents with anti-restenosis properties at the implantation site. Most of them use polymer coating as a drug carrier, but concerns about long-term negative effects of a permanent polymer coating have stimulated the development of non-polymer DES or DES based on bioabsorbable polymers. Several randomized studies with DES have demonstrated their superiority over bare metal stents mostly in selected patients and lesion subsets. Accumulating evidence is showing significant differences in performance between currently used DES. These differences are more pronounced in complex, high-risk subsets of patients and lesions and should be considered during the process of DES selection for the individual patient. Interventional cardiologists have learned that patients who receive DES require a more prolonged antiplatelet therapy, but the optimal length and regimen are still unclear and further investigations are needed. Major advances in interventional cardiology have caused a dramatic shift away from aorto-coronary bypass surgery and an increase in the complexity of percutaneous coronary interventions. Observational and specifically designed randomized studies are currently addressing the issue of the role of DES in complex situations including in-stent restenosis, ostial and bifurcation lesions, chronic occlusions, small vessels, long lesions, saphenous vein grafts, multivessel disease, left main disease, acute myocardial infarction and diabetes mellitus. Although definitive answers are still to come from ongoing research, available data support the use of DES in most of these situations.

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is not associated with restenosis after coronary stent placement.

BACKGROUND: The renin-angiotensin system is thought to play a role in coronary thrombosis and restenosis. Plasma angiotensin I-converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. The objective of this study was to test the hypothesis that the D allele of the ACE gene is associated with a higher risk for restenosis after coronary stent placement. METHODS AND RESULTS: This prospective study included 1850 consecutive patients with coronary artery disease who underwent intracoronary stent implantation. The adverse clinical events recorded were death, myocardial infarction, and target vessel revascularization. The primary end point of the study was restenosis (>/=50% diameter stenosis at follow-up angiography performed in 84% of the patients). The secondary end point was clinical outcome 1 year after the procedure. The restenosis rate at the 6-month angiographic follow-up was 32.8% in patients with the II genotype, 34.0% for patients with the ID genotype, and 31.2% for patients with the DD genotype (P=0.62). One-year event-free survival was 77.7% in patients with genotype II, 75.2% in patients with genotype ID, and 75.5% in patients with genotype DD (P=0.54). The lack of association was also present in the subgroup of patients with a low risk for restenosis: the restenosis rate was 21.7% in II carriers, 23.4% in ID carriers, and 19.7% in DD carriers (P=0.83). CONCLUSIONS: The ACE DD genotype or D allele does not influence the 1-year clinical and angiographic outcome of patients undergoing coronary stent placement. These data suggest that routine determination of the ACE genotype may not help identify patients who are at a higher risk of thrombotic and restenotic events after coronary stent placement.

Prognostic value of the modified american college of Cardiology/American heart association stenosis morphology classification for long-term angiographic and clinical outcome after coronary stent placement.

Background-The modified American College of Cardiology/American Heart Association (ACC/AHA) lesion morphology criteria are predictive of early outcome after various coronary catheter interventions. Their potential prognostic value after stent implantation and, in particular, for restenosis and long-term clinical outcome has not been studied. We assessed the prognostic value of the modified ACC/AHA criteria for the long-term angiographic and clinical outcome of patients after coronary stenting. Methods and Results-This study includes 2944 consecutive patients with symptomatic coronary artery disease treated with coronary stent placement. Modified ACC/AHA lesion morphology criteria were used to qualitatively assess the angiograms; type A and B1 lesions were categorized as simple, and type B2 and C lesions were designated complex. Primary end points were angiographic restenosis and 1-year event-free survival. Restenosis rate was 33.2% in complex lesions and 24.9% in simple lesions (P<0.001). It was 21. 7% for type A, 26.3% for type B1, 33.7% for type B2, and 32.6% for type C lesions. One-year event-free survival was 75.6% for patients with complex lesions and 81.1% for patients with simple lesions (P<0. 001). It was 85.2% for patients with type A, 79.4% for type B1, 75. 9% for type B2, and 75.2% type C lesions. The higher risk for restenosis and an adverse outcome associated with complex lesions was also maintained after multivariate adjustment for other clinical and angiographic characteristics. Conclusions-The modified ACC/AHA lesion morphology scheme has significant prognostic value for the outcome of patients after coronary stent placement. Lesion morphology is able to influence the restenosis process and thus the entire 1-year clinical course of these patients.

A randomized trial comparing stenting with balloon angioplasty in small vessels in patients with symptomatic coronary artery disease. ISAR-SMART Study Investigators. Intracoronary Stenting or Angioplasty for Restenosis Reduction in Small Arteries.

BACKGROUND: More than 30% of the lesions currently treated with interventional approaches are situated in vessels smaller in size than those representing an established indication for stenting. The objective of this randomized trial was to assess whether compared with PTCA, stenting of small coronary vessels is associated with a reduction of restenosis. METHODS AND RESULTS: Patients with symptomatic coronary artery disease with lesions situated in native coronary vessels between 2 and 2.8 mm in size were randomly assigned to be treated with either stenting (n=204) or PTCA (n=200). Adjunct therapy consisted of abciximab, ticlopidine, and aspirin. Repeat angiography at 6-month follow-up was performed in 83% of the patients. The primary end point of the study was the incidence of angiographic restenosis (>/=50% diameter stenosis) at follow-up; adverse clinical events, such as death, myocardial infarction, stroke, or target vessel revascularization, were assessed as secondary end points. After 7 months, there were no significant differences in the infarct-free survival rates between the 2 study groups: 96.6% for stent patients, and 97.0% for PTCA patients (P:=0. 80). Target vessel revascularization was needed in 20.1% of the stent patients and 16.5% of the PTCA patients (P:=0.35). The primary end point of angiographic restenosis was found in 35.7% of the stent patients and 37.4% of the PTCA patients (P:=0.74). The net lumen gain observed at follow-up was identical (0.76+/-0.78 in the stent group versus 0.76+/-0.63 mm in the PTCA group, P:=0.93). CONCLUSIONS: Stenting and PTCA are associated with equally favorable results when used for treating lesions in small coronary vessels.

Increased risk of restenosis after placement of gold-coated stents: results of a randomized trial comparing gold-coated with uncoated steel stents in patients with coronary artery disease.

BACKGROUND: Gold is a highly biocompatible material. Experimental evidence suggests that coating the stent with a gold layer may have a beneficial influence. In this randomized trial, we assessed whether gold-coated stents were associated with a better clinical and angiographic outcome after coronary placement. METHODS AND RESULTS: Patients with symptomatic coronary artery disease were randomly assigned to receive either a gold-coated Inflow stent (n = 367) or an uncoated Inflow stainless steel stent (n = 364) of identical design. Follow-up angiography was routinely performed at 6 months. The primary end point of the study was the occurrence of any adverse clinical event (death, myocardial infarction, or target-vessel revascularization) during the first year after stenting. At 30 days, there was no significant difference in the combined incidence of adverse events, with 7.9% in the gold-stent group versus 5.8% in the steel-stent group (P = 0.25). The incidence of angiographic restenosis (> or =50% diameter stenosis) was 49.7% in the gold-stent group and 38.1% in the steel-stent group (P = 0.003). One-year survival free of myocardial infarction was 88.6% in the gold-stent group and 91.8% in the steel-stent group (P = 0.14). One-year event-free survival was significantly less favorable in the gold-stent group (62.9% versus 73.9% in the steel-stent group; P = 0.001). CONCLUSIONS: Coating steel stents with gold had no significant influence on the thrombotic events observed during the first 30 days after the intervention. However, gold-coated stents were associated with a considerable increase in the risk of restenosis over the first year after stenting.

Inhibition of neointima formation after experimental coronary artery stenting: a new biodegradable stent coating releasing hirudin and the prostacyclin analogue iloprost.

BACKGROUND: To minimize acute stent thrombosis and development of restenosis, stents coated with biodegradable and nonbiodegradable polymers have been proposed to serve as sustained-release drug carriers. METHODS AND RESULTS: In both a sheep and a pig model, we examined the vascular response to standard and high-pressure implantation of coronary Palmaz-Schatz stents coated with a 10-microm layer of polylactic acid (MW 30 kDa) releasing recombinant polyethylene glycol (r-PEG)-hirudin and the prostacyclin analogue iloprost, both drugs with antithrombotic and potentially antiproliferative effects. Study observation time was 28 days. Between the corresponding stent groups, no differences were observed with regard to preplacement and postplacement implantation parameters. The morphometric analysis demonstrated that the coating was associated with a greater lumen diameter through a reduction in the mean restenosis area by 22.9% (P<0.02) in the standard-pressure model (sheep) and by 24.8% (P<0.02) in the overstretch pig model compared with uncoated control stents without inducing a local inflammatory response. CONCLUSIONS: The results from this study demonstrate beneficial effects of a polymeric stent coating with polylactic acid releasing r-PEG-hirudin and iloprost on the development of restenosis after coronary stent placement at 4 weeks, independent of the extent of vascular injury. Future studies are proposed to investigate the integration of other substances to further enhance the potential of the stent coating on reducing neointimal formation.

Enhanced cardiac contractility after gene transfer of V2 vasopressin receptors In vivo by ultrasound-guided injection or transcoronary delivery.

BACKGROUND: Systemic levels of arginine vasopressin (AVP) are increased in congestive heart failure, resulting in vasoconstriction and reduced cardiac contractility via V(1) vasopressin receptors. V(2) vasopressin receptors (V2Rs), which promote activation of adenylyl cyclase, are physiologically expressed only in the kidney and are absent in the myocardium. Heterologous expression of V2Rs in the myocardium could result in a positive inotropic effect by using the endogenous high concentrations of AVP in heart failure. METHODS AND RESULTS: We tested gene transfer with a recombinant adenovirus for the human V2R (Ad-V2R) to stimulate contractility of rat or rabbit myocardium in vivo. Ultrasound-guided direct injection or transcoronary delivery of adenovirus in vivo resulted in recombinant receptor expression in the myocardial target area, leading to a substantial increase in [(3)H]AVP binding. In 50% of the cardiomyocytes isolated from the directly injected area, single-cell shortening measurements detected a significant increase in contraction amplitude after exposure to AVP or the V2R-specific desmopressin (DDAVP). Echocardiography of the target myocardial area documented a marked increase in local fractional shortening after systemic administration of DDAVP in V2R-expressing animals but not in control virus-treated hearts. Simultaneous measurement of global contractility (dP/dt(max)) confirmed a positive inotropic effect of DDAVP on left ventricular function in the Ad-V2R-injected animals. CONCLUSIONS: Adenoviral gene transfer of the V2R into the myocardium increases cardiac contractility in vivo. Heterologous expression of cAMP-forming receptors in the myocardium could lead to novel strategies in the therapy of congestive heart failure by bypassing the desensitized beta-adrenergic receptor-signaling cascade.

Influence of balloon pressure during stent placement in native coronary arteries on early and late angiographic and clinical outcome: A randomized evaluation of high-pressure inflation.

BACKGROUND: High-pressure dilatation is considered a better stent placement strategy, but this has not yet been proved by appropriately designed studies. The objective of this randomized trial was to assess the role of high-pressure dilatation in the early and late outcome of patients undergoing coronary stent placement. METHODS AND RESULTS: Consecutive patients with coronary stent placement were randomly assigned to high- (15 to 20 atm, 468 patients) or low- (8 to 13 atm, 466 patients) balloon-pressure dilatation. The primary end point of the study was the event-free survival at 1 year. Secondary end points were the incidence of stent thrombosis at 30 days and angiographic restenosis (>/=50% diameter stenosis) at 6 months. The incidence of stent thrombosis was 1.7% in the high-pressure and 1.9% in the low-pressure group (relative risk 0.89; 95% CI 0.30 to 2.56). During the first 30 days, although there was no significant difference in the incidence of Q-wave myocardial infarction, the incidence of non-Q-wave infarction was 6.4% in the high-pressure and 3.4% in the low-pressure group (relative risk 1. 87; 95% CI 1.02 to 3.42). The restenosis rate was 30.4% in the high-pressure and 31.4% in the low-pressure group (relative risk 0. 97; 95% CI 0.75 to 1.26). Event-free survival at 1 year was not significantly different between the groups, with 78.8% in high-pressure patients and 75.5% in patients assigned to low-pressure dilatation (hazard ratio 0.85; 95% CI 0.65 to 1.11). CONCLUSIONS: The systematic use of high-balloon-pressure inflation (15 to 20 atm) during coronary stent placement is not associated with any significant influence on the 1-year outcome of patients undergoing this intervention.

PlA polymorphism of platelet glycoprotein IIIa and risk of restenosis after coronary stent placement.

BACKGROUND: Platelets play a central role in the process of restenosis after percutaneous coronary interventions. A polymorphism of platelet glycoprotein IIIa (PlA) has been associated with a higher risk of coronary thrombosis. We designed this prospective study to test the hypothesis that PlA polymorphism of glycoprotein IIIa is associated with an increased risk for restenosis after coronary stent placement. METHODS AND RESULTS: The study included 1150 consecutive patients with successful coronary stent placement and 6-month follow-up with coronary angiography. The end point of the study was the incidence of angiographic restenosis (>/=50% diameter stenosis) at follow-up. Of the 1150 patients, 72.5% were homozygous for PlA1, 24.7% were heterozygous (PlA1/A2), and 2.8% were homozygous for PlA2. Patients with the PlA2 allele demonstrated a significantly higher restenosis rate than did those without (47% versus 38%; OR, 1.42; 95% CI, 1.09 to 1.84). The risk was highest in homozygous carriers of PlA2 (53.1% restenosis rate). After adjustment for several clinical and angiographic characteristics, the presence of the PlA2 allele remained a significantly independent risk factor for restenosis (adjusted OR, 1.35; 95% CI, 1.07 to 1.70). The influence of the PlA2 allele on restenosis was stronger in women. Women with PlA2 had a restenosis rate of 52% compared with the 33% incidence among women homozygous for PlA1 (OR, 2.21; 95% CI, 1.27 to 3.85). CONCLUSIONS: This study showed a significant association between the PlA polymorphism of glycoprotein IIIa and the risk of restenosis after coronary stent placement. The risk was more pronounced in patients homozygous for PlA2 allele and in female patients.

Clinical experience with a novel multielectrode basket catheter in right atrial tachycardias.

BACKGROUND: The complexity of atrial tachycardias (ATs) makes the electroanatomic characterization of the arrhythmogenic substrate difficult with conventional mapping techniques. The aim of our study was to evaluate possible advantages of a novel multielectrode basket catheter (MBC) in patients with AT. METHODS AND RESULTS: In 31 patients with AT, an MBC composed of 64 electrodes was deployed in the right atrium (RA). The possibility of deployment, spatial relations between MBC and RA, MBC recording and pacing capabilities, mapping performance, and MBC-guided ablation were assessed. MBC deployment was possible in all 31 patients. The MBC was left in the RA for 175+/-44 minutes. Stable bipolar electrograms were recorded in 88+/-4% of electrodes. Pacing from bipoles was possible in 64+/-5% of electrode pairs. The earliest activity intervals, in relation to P-wave onset, measured from the MBC and standard roving catheters were 41+/-9 and 46+/-6 ms, respectively (P=0.21). Radiofrequency ablation was successful in 15 (94%) of 16 patients in whom it was attempted, including 2 patients with polymorphic right atrial tachycardia (RAT), 2 with RAT-atrial flutter combination, 1 with macroreentrant AT, and 1 with focal origin of atrial fibrillation. CONCLUSIONS: These data demonstrate that MBC can be used safely in patients with right atrial arrhythmias. The simultaneous multielectrode mapping aids in the rapid identification of sites of origin of the AT and facilitates radiofrequency ablation procedures. The technique is especially effective for complex atrial arrhythmias.

Previous cytomegalovirus infection and restenosis after coronary stent placement.

BACKGROUND: Reactivated cytomegalovirus may promote neointima formation after percutaneous coronary interventions by facilitating cell cycle progression through inhibition of the eukariotic tumor suppressor protein p53. This prospective study sought to investigate the effect of previous cytomegalovirus infection on restenosis after coronary stenting. METHODS AND RESULTS: In 551 consecutive patients with successful stent placement, we determined cytomegalovirus IgG titers. Primary and secondary end points were the rate of angiographic restenosis at 6 months and the rate of target vessel reintervention at 1 year, respectively. Three hundred forty patients (62%) had a positive cytomegalovirus IgG titer. We obtained angiographic follow-up in 82% of all patients. Angiographic restenosis rate was 28.7% in patients with positive cytomegalovirus titers and 34.6% in patients with negative titers (P=0.18). Between the groups with and without positive cytomegalovirus titers, there were no significant differences in late lumen loss (1.16+/-0.90 mm and 1.23+/-0.86 mm, respectively, P=0.44). Target vessel reintervention was performed in 16.8% of the patients with positive cytomegalovirus titers and in 17.5% of those without (P=0.82). Even after correction for potential confounding variables by multivariate analysis, positive cytomegalovirus titers did not manifest as a predictor of angiographic restenosis (adjusted odds ratio [95% confidence interval], 0.78 [0.52 to 1.19]). CONCLUSIONS: Previous cytomegalovirus infection does not carry an increased risk of restenosis after stenting.

Gene expression profiling of human stent-induced neointima by cDNA array analysis of microscopic specimens retrieved by helix cutter atherectomy: Detection of FK506-binding protein 12 upregulation.

BACKGROUND: Restenosis due to neointima formation is the major limitation of stent-supported balloon angioplasty. Despite abundant animal data, molecular mechanisms of neointima formation have been investigated on only a limited basis in patients. This study sought to establish a method for profiling gene expression in human in-stent neointima and to identify differentially expressed genes that may serve as novel therapeutic targets. METHODS AND RESULTS: We retrieved tissue specimens from patients with symptomatic in-stent restenosis using a novel helix cutter atherectomy device. cDNA samples prepared from neointima (n=10) and, as a control, from the media of normal arteries (n=14) were amplified using a novel polymerase chain reaction protocol and hybridized to cDNA arrays. Immunohistochemistry characterized the atherectomy material as neointima. cDNA arrays readily identified differentially expressed genes. Some of the differentially expressed genes complied with expected gene expression patterns of neointima, including downregulation of desmin and upregulation of thrombospondin-1, cyclooxygenase-1, and the 70-kDa heat shock protein B. Additionally, we discovered previously unknown gene expression patterns, such as downregulation of mammary-derived growth inhibitor and upregulation of FK506-binding protein 12 (FKBP12). Upregulation of FKBP12 was confirmed at the protein level in neointimal smooth muscle cells. CONCLUSIONS: Gene expression patterns of human neointima retrieved by helix-cutter atherectomy can be reliably analyzed by cDNA array technology. This technique can identify therapeutic targets in patients, as exemplified by the findings regarding FKBP12. FKBP12 is the receptor for Rapamycin (sirolimus), which in animal models reduced neointima formation. Our study thus yields a rationale for the use of Rapamycin to prevent restenosis in patients.

Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO) trial.

BACKGROUND: Increased thrombogenicity and smooth muscle cell proliferative response induced by the metal struts compromise the advantages of coronary stenting. The objective of this randomized, multicenter study was to assess whether a reduced strut thickness of coronary stents is associated with improved follow-up angiographic and clinical results. METHODS AND RESULTS: A total of 651 patients with coronary lesions situated in native vessels >2.8 mm in diameter were randomly assigned to receive 1 of 2 commercially available stents of comparable design but different thickness: 326 patients to the thin-strut stent (strut thickness of 50 microm) and 325 patients to the thick-strut stent (strut thickness of 140 microm). The primary end point was the angiographic restenosis (>/=50% diameter stenosis at follow-up angiography). Secondary end points were the incidence of reinterventions due to restenosis-induced ischemia and the combined rate of death and myocardial infarctions at 1 year. The incidence of angiographic restenosis was 15.0% in the thin-strut group and 25.8% in the thick-strut group (relative risk, 0.58; 95% CI, 0.39 to 0.87; P=0.003). Clinical restenosis was also significantly reduced, with a reintervention rate of 8.6% among thin-strut patients and 13.8% among thick-strut patients (relative risk, 0.62; 95% CI, 0.39 to 0.99; P=0.03). No difference was observed in the combined 1-year rate of death and myocardial infarction. CONCLUSIONS: The use of a thinner-strut device is associated with a significant reduction of angiographic and clinical restenosis after coronary artery stenting. These findings may have relevant implications for the currently most widely used percutaneous coronary intervention.

The conduction and cardiac sympathetic systems: metabolic aspects.

Compared with the myocardium, glycolytic enzymes are reduced by 50% and mitochondrial enzymes and space by 70% in the conduction system of the calf heart. In addition, on the basis of adenosine triphosphate activities energy demands are reduced by more than 50%; this is in parallel with the reduction in myofibrillar space. The increased tolerance of the conduction system against ischemia can be explained by a reduction of energy demands and a higher proportion of (anaerobic) glycolytic as opposed to aerobic mitochondrial energy production. Among the structures of the conduction system, the sinoatrial and atrioventricular nodes are markedly susceptible to hypoxia in contrast to atrial conduction and ventricular conduction by way of the His-Purkinje system. In the isolated perfused rat heart, an increased net release of noradrenaline during the first 10 minutes of ischemia is only noted after sympathetic stimulation. During this phase, catecholamine overflow is limited by the activity of the neuronal reuptake. At a later second phase, from 15 to 40 minutes after the onset of ischemia, the mechanism of noradrenaline net release is carrier-mediated efflux inhibited by neuronal uptake blocking agents. During the third phase of ischemia, after about 40 minutes, spontaneous noradrenaline release is greatly augmented, probably as a result of leakage caused by membrane damage.