A three-gene DNA methylation biomarker accurately classifies early stage prostate cancer.

BACKGROUND: We identify and validate accurate diagnostic biomarkers for prostate cancer through a systematic evaluation of DNA methylation alterations. MATERIALS AND METHODS: We assembled three early prostate cancer cohorts (total patients = 699) from which we collected and processed over 1300 prostatectomy tissue samples for DNA extraction. Using real-time methylation-specific PCR, we measured normalized methylation levels at 15 frequently methylated loci. After partitioning sample sets into independent training and validation cohorts, classifiers were developed using logistic regression, analyzed, and validated. RESULTS: In the training dataset, DNA methylation levels at 7 of 15 genomic loci (glutathione S-transferase Pi 1 [GSTP1], CCDC181, hyaluronan, and proteoglycan link protein 3 [HAPLN3], GSTM2, growth arrest-specific 6 [GAS6], RASSF1, and APC) showed large differences between cancer and benign samples. The best binary classifier was the GAS6/GSTP1/HAPLN3 logistic regression model, with an area under these curves of 0.97, which showed a sensitivity of 94%, and a specificity of 93% after external validation. CONCLUSION: We created and validated a multigene model for the classification of benign and malignant prostate tissue. With false positive and negative rates below 7%, this three-gene biomarker represents a promising basis for more accurate prostate cancer diagnosis.

Long-term outcome of unprotected left main stenting: a Canadian tertiary care experience.

BACKGROUND: Coronary stenting is increasingly used to treat unprotected left main disease in selected patients. However, there is a paucity of data on the long-term outcome of these patients in a Canadian context outside of clinical trials. METHODS: We retrospectively reviewed all provincially-insured patients undergoing left main coronary stenting at a large tertiary referral centre from 2000-2011. Pre-procedural angiograms were reviewed to identify the location of left main disease, and extent of concomitant coronary disease quantified by calculating Synergy Between Percutaneous Coronary Intervention With TAXUS Drug-Eluting Stent and Cardiac Surgery (SYNTAX) scores for each patient. In-hospital death and major adverse cardiac event (MACE) rates were evaluated as were long-term death and MACE rates obtained via linkage of our institutional registry with the Ontario health claims database. RESULTS: Two hundred twenty-one patients underwent unprotected left main stenting with 29 (13.1%) in-hospital death and 34 (15.4%) a MACE. At an average follow-up of 3.1 ± 2.8 years, 109 patients (49.3%) died and 151 (68.3%) experienced a MACE. Higher SYNTAX tertile and use of bare metal rather than drug-eluting stents was associated with increased rates of in-hospital and long-term death. CONCLUSIONS: This study reports, to our knowledge, the largest Canadian cohort of unprotected left main stenting over more than a decade. Coronary stenting was associated with acceptable in-hospital event rates, but poor long-term outcomes, reflecting the higher-risk population traditionally selected for this procedure.

Association between drug-eluting stent type and clinical outcomes in patients with chronic kidney disease undergoing percutaneous coronary intervention.

BACKGROUND: The comparative efficacy of first- vs second-generation drug-eluting stents (DESs) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) is unknown. METHODS: A retrospective analysis of consecutive patients undergoing PCI at a tertiary PCI center from 2007-2011 was performed, with linkage to administrative databases for long-term outcomes. CKD was defined as creatinine clearance (CrCl) < 60 mL/min. Propensity matching by multivariable scoring method and Kaplan-Meier analyses were performed. RESULTS: Of 6481 patients with available CrCl values undergoing a first PCI during the study period, 1658 (25%) had CKD. First- and second-generation DESs were implanted in 320 (19.3%) and 128 (7.7%) patients with CKD, respectively. At 2 years, no significant differences were observed between first-generation (n = 126) and second-generation (n = 126) propensity-matched DES cohorts for the outcomes of death (19% vs 16%; P = 0.51), repeat revascularization (10% vs 10%; P = 1.00), and major adverse cardiovascular and cerebrovascular events (MACCE) (36% vs 37%; P = 0.90). The 2-year Kaplan-Meier survival was also similar (P = 0.77). In patients with CKD, second-generation DES type was not an independent predictor for death (P = 0.49) or MACCE (P = 1.00). CONCLUSIONS: Although the use of first- and second-generation DESs was associated with similar 2-year safety and efficacy in patients with CKD, our results cannot rule out a beneficial effect of second- vs first-generation DESs owing to small sample size. Future studies with larger numbers of patients with CKD are needed to identify optimal stent types, which may improve long-term clinical outcomes.

Antithrombotic therapy after coronary stenting in patients with nonvalvular atrial fibrillation.

BACKGROUND: The safety and efficacy of triple therapy (TT; warfarin with dual antiplatelet therapy [DAPT]) in post-percutaneous coronary intervention (PCI) patients with atrial fibrillation (AF) are unclear. We aimed to determine whether TT is associated with a decreased stroke rate and an acceptable bleeding rate in this population. METHODS: This was a single-centre, retrospective study. Primary composite outcome was death, ischemic stroke, or transient ischemic attack. Secondary outcomes included components of primary outcome, bleeding, and blood transfusion rates. RESULTS: Of 602 post-PCI patients with AF between 2000 and 2009, 382 received TT, 220 DAPT. Mean follow-up post PCI was 5.9 ± 5.0 months. The TT group had a higher CHADS(2) score (2.6 vs 2.1, P < 0.001), older age (72.9 vs 70.5 years, P = 0.039), more heart failure (72.3% vs 36.9%, P = 0.010), and more strokes (14.4% vs 6.4%, P = 0.010). Neither primary outcome, major bleeding, nor blood transfusion rates differed between treatment groups, but more gastrointestinal bleeding occurred with TT use (2.6% vs 0.5%, P = 0.045). Net clinical benefit was -5.2 (CHADS(2) ≤ 2), 0.9 (CHADS(2) > 2), and -3.2 (overall) per 100 patient-years. CONCLUSIONS: Although we found no association with TT usage and a reduction in cerebrovascular ischemic or major bleeding events in post-PCI patients with AF regardless of CHADS(2) score vs DAPT, the study was likely underpowered to demonstrate a clinically relevant reduction. TT was associated with a 5-fold increase in gastrointestinal bleeding vs DAPT. Net clinical benefit calculations suggest benefits of TT in patients with CHADS(2) > 2. Stratification with CHADS(2) might be useful to determine the optimal antithrombotic therapy post PCI.

Choice of stent and outcomes after treatment of drug-eluting stent restenosis in highly complex lesions.

OBJECTIVES: Our aim was to compare the outcomes of a same versus different drug-eluting stent (DES) implantation strategy for the treatment of DES instent restenosis (ISR). BACKGROUND: The absence of clear data renders the treatment of DES ISR one of the most challenging situations in interventional cardiology. METHODS: We identified all cases of DES ISR treated with a second DES between January 2004 and January 2009. The lesions were divided into those treated with the same DES as the initial one that restenosed and those treated with a different DES. The main end-point was repeat target lesion revascularization (TLR). RESULTS: We included 116 patients with a total of 132 lesions. The patient population was highly complex: 55.5% with diabetes, 56% with type-C lesions, 15.9% with lesions previously stented with BMS and 18.2% with fluoroscopic evidence of stent fracture. A same and different stent strategy was conducted in 41 lesions (31%) and 91 lesions (69%), respectively. Overall TLR was 31.1% and occurred in 46.3% of patients treated with the same stent and 24.4% of those with a different stent (P = 0.012). Multivariable analysis found same stent strategy (OR 2.84, 95%CI 1.23-6.57;P = 0.014) and occurrence of stent fracture (OR 4.03, 95%CI 1.33-12.01;P = 0.012) to be the only independent predictors of TLR after a median follow-up of 20.4 [12.1-30.2] months. CONCLUSIONS: In highly complex lesions, DES implantation for DES ISR is linked to a high need of future revascularization. An association between implanting a DES type other than the original and lower rate of TLR is suggested.

Decreased risk of stent fracture-related restenosis between paclitaxel-eluting stents and sirolimus eluting stents: results of long-term follow-up.

OBJECTIVE: To compare the outcomes between paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) for the treatment of drug-eluting stent (DES) fracture. BACKGROUND: DES fracture is considered as an important predictor of in-stent restenosis (ISR). However, little data are available evaluating the optimal treatment for this complication of coronary stenting. METHODS: From January 1, 2004 to December 31, 2008, patients with DES ISR treated with a second DES were identified and evaluated for stent fracture. Stent fracture was defined by the presence of strut separation in multiple angiographic projections, assessed by two independent reviewers. Target lesion revascularization (TLR) at 6 and 12 months were the primary end points. RESULTS: Of 131 lesions with DES ISR treated with a second DES, we found 24 patients (24 lesions, 18.2%) with angiographically confirmed stent fracture. Of these, 20 patients (20 lesions) treated with either PES (n = 11/55%) or SES (n = 9/45%) were included in the study. TLR at 6 months occurred in 9% of patients treated with PES and 22% of those treated with SES (P = 0.41). After 12 months, TLR was 9% and 55.5%, respectively (P = 0.024). CONCLUSIONS: This study demonstrates a high incidence of stent fracture in patients presenting with DES ISR in need of further treatment with another DES. The suggested association between treatment of stent fracture-associated DES ISR with PES as compared with SES, and better long-term outcomes, is in need of confirmation by larger prospective registries and randomized trials.

In-hospital outcomes of very elderly patients (85 years and older) undergoing percutaneous coronary intervention.

OBJECTIVE: To compare in-hospital outcomes of a large cohort of very elderly patients (age ≥ 85 years) with younger patients (age < 85 years) undergoing percutaneous coronary intervention (PCI) for all indications at our institution. BACKGROUND: Interventionist cardiologists are often reluctant to undertake PCI in very elderly patients due to the perception of poor outcome in this high-risk cohort. However, the prognostic significance of advanced age itself is not clear. METHODS: Baseline clinical, angiographic and procedural variables, and in-hospital outcome data were entered into a prospective registry of 17,572 consecutive patients undergoing PCI at the University Health Network between April 2000 and December 2008. Patients were stratified according to age (< 85 years, n = 17,168, or ≥ 85 years, n = 404) and in-hospital mortality, major adverse cardiac events (MACE), and complication rates were calculated. Logistic regression-analysis identified independent predictors of unadjusted mortality and MACE. Very elderly patients were propensity matched with younger patients (1:2 ratio), and the analysis repeated. RESULTS: Very elderly patients had a mean age of 87.5 ± 2.9 (range, 85-97 years) vs. 62.8 ± 11.1 years for the younger cohort and had a greater number of comorbid conditions. This cohort were more likely to present as an urgent or primary PCI, underwent more complex interventions, and achieved less angiographic success. Unadjusted mortality and post procedure myocardial infarction were significantly higher in very elderly patients (6.93% vs. 1.20%, P < 0.0001 and 4.46% vs. 2.74%, P = 0.04). Renal, neurological, and access-site complications were all greater in the very elderly cohort. Although age ≥ 85 years was a significant independent predictor of both mortality (OR, 2.62; CI, 1.44-4.78, P = 0.0016) and MACE (OR, 1.94; CI, 1.25-3.01, P = 0.003), other variables such as cardiogenic shock were more potent predictors of adverse outcomes. CONCLUSION: Very elderly patients represent a high-risk cohort, with significantly increased in-hospital mortality and complication rates after PCI. Death occurred predominantly in very elderly patients undergoing nonelective PCI. Decisions to proceed with PCI in very elderly patients should be based on other prognostic variables in combination with advanced age, and these patients should not be excluded from revascularization based on age alone.

Late outcomes following percutaneous coronary interventions: results from a large, observational registry.

BACKGROUND: Randomized controlled trials report short- and medium- term outcomes following percutaneous coronary intervention (PCI), but their applicability to the general population is not known. Data regarding the long-term clinical outcomes of patients undergoing PCI are lacking. OBJECTIVE: To determine the long-term outcomes of 'all-comers' undergoing PCI at a large-volume tertiary cardiac referral centre. METHODS: A total of 12,662 consecutive patients undergoing an index procedure and entered into the University Health Network's (Toronto, Ontario) prospective registry between April 2000 and September 2007 were identified. In-hospital outcomes were assessed. Follow-up data were obtained through linkage to a provincial registry. Kaplan-Meier analysis was performed to calculate unadjusted survival rates, and Cox multiple regression analysis identified independent predictors of late mortality, major adverse cardiac events and all cardiovascular events. RESULTS: The population included a relatively high-risk patient cohort, with 19% older than 75 years of age, 28% with diabetes, 61% with multivessel disease and 1.3% in cardiogenic shock. Urgent procedures comprised 53% of all cases. The all-cause mortality rate at seven years follow-up was 10.6%. Repeat PCI occurred in 14.2% of patients, and coronary artery bypass grafting in 4.2%. Men showed a significant unadjusted survival advantage compared with women. Procedural characteristics such as incomplete revascularization and residual stenosis, in addition to established risk factors, were predictors of poorer long-term outcomes. Cardiogenic shock was the strongest predictor of late mortality. CONCLUSION: In the present large registry of 'all-comers' for PCI, longterm major adverse cardiac event rates were low and consistent with outcomes from randomized controlled trials. These data reflect a large cohort in real-world clinical practice, and may help clinicians further characterize and better treat high-risk patients who are undergoing PCI.

Selective use of embolic protection devices during saphenous vein grafts interventions: a single-center experience.

OBJECTIVES: To report on outcomes with selective use of embolic protection devices (EPD) during percutaneous coronary intervention (PCI) to saphenous vein grafts (SVG). BACKGROUND: PCI to SVG is associated with increased risk and the use of EPD is recommended in this setting. METHODS: Angiographic and clinical outcomes were prospectively obtained from 534 consecutive patients who underwent PCI to SVG with or without EPD at a tertiary cardiac centre. Long-term outcomes were obtained by linkage to a provincial registry. RESULTS: EPD, deployed in 198 of 373 SVGs (53%) suitable for deployment of a distal EPD, were used more often in ectatic (33% vs. 19%, P = 0.003), ulcerated (17% vs. 9%, P = 0.03), thrombotic (26% vs. 10%, P < 0.0001) vein grafts, with longer degenerated segments (P = 0.002), and in lesions involving the body of the graft (85% vs. 66%, P < 0.0001), and less with lesions involving the graft ostium (29% vs. 44%, P = 0.003). Patients suitable for but not receiving EPD tended to be more likely to have a periprocedural myocardial infarction. During 3 years of follow-up, 49% of the patients had a cardiovascular event. Cumulative mortality was 8.4%, 18.8% and 14.7% in patients unsuitable for distal EPD, suitable but without EPD, and with EPD (p = 0.11). Nonuse of EPD was an independent predictor of MACE at 3 years. (P = 0.02). CONCLUSIONS: Selective use of EPD is associated with low in-hospital cardiovascular event rates. Long-term outcomes are manifested by a high rate of events, especially in patients with SVG's suitable for but not receiving EPD. This suggests that routine use of distal EPD may be warranted in unselected patients with suitable SVG anatomy.

The adverse long-term impact of renal impairment in patients undergoing percutaneous coronary intervention in the drug-eluting stent era.

BACKGROUND: An observational study determining the long-term impact of chronic kidney disease (CKD) on patients undergoing percutaneous coronary intervention at a tertiary cardiac referral center. CKD is associated with poor in-hospital outcomes after percutaneous coronary intervention, but its effect beyond 1 year, particularly in the drug-eluting stent (DES) era, has not been reported. METHODS AND RESULTS: Baseline creatinine was available for 11,953 patients entered into a prospective registry (April 2000 to September 2007). Patients were stratified: those with or without at least moderate CKD (creatinine clearance, <60 mL/min). Follow-up data were obtained through linkage to a provincial registry. Kaplan-Meier analysis was performed. Cox multiple-regression analysis identified independent predictors of late mortality and major adverse cardiac events (MACE) and examined the association between DES use and late outcomes in the presence or absence of CKD. CKD was present in 3070 patients (25.7%). In-hospital mortality and MACE were significantly increased in CKD (3.34% versus 0.44%, P<0.001 and 5.73% versus 2.2%, P<0.001). Survival and MACE-free survival at 7 years were reduced (64.5+/-1.4% versus 89.4+/-0.5%, P<0.001; 44.0+/-1.4% versus 63.4+/-0.8%, P<0.001). CKD was an independent predictor of late mortality and MACE (hazard ratio [HR]: 2.18, CI: 1.90 to 2.49, P<0.0001; HR: 1.37, CI: 1.25 to 1.49, P<0.0001). DES use was associated with a significant reduction in both (HR: 0.71, CI: 0.60 to 0.83, P<0.0001; HR: 0.70, CI: 0.63 to 0.78, P<0.0001). In patients with CKD, DES use was associated with reduced revascularization (HR: 0.68, CI: 0.53 to 0.88, P=0.004) and reduced MACE (HR: 0.81, CI: 0.69 to 0.95, P=0.011) but not reduced mortality (HR: 0.85, CI: 0.69 to 1.05, P=0.1). CONCLUSIONS: In a large registry of "all comers" for percutaneous coronary intervention, CKD was an independent predictor of adverse late outcomes. DES use may be associated with improved long-term outcomes in this high-risk cohort, but further prospective studies are required.

The Toronto score for in-hospital mortality after percutaneous coronary interventions.

BACKGROUND: Benchmarking the performance of providers is an increasing priority in many health care economies. In-hospital mortality represents an important and uniformly assessed measure on which to examine the outcome of percutaneous coronary intervention (PCI). Most existing prediction models of in-hospital mortality after PCI were derived from 1990s data, and their current relevance is uncertain. METHODS: From consecutive PCIs performed during 2000-2008, derivation and validation cohorts of 10,694 and 5,347 patients, respectively, were analyzed. Logistic regression for in-hospital death yielded integer risk weights for each independent predictor variable. These were summed for each patient to create the Toronto PCI risk score. RESULTS: Death occurred in 1.3% of patients. Independent predictors with associated risk weights in parentheses were as follows: age 40 to 49 y (1), 50 to 59 y (2), 60 to 69 y (3), 70 to 79 y (4), and > or =80 y (5); diabetes (2); renal insufficiency (2); New York Heart Association class 4 (3); left ventricular ejection fraction <20% (3); myocardial infarction in the previous month (3); multivessel disease (1); left main disease (2); rescue or facilitated PCI (3); primary PCI (4); and shock (6). The model had a receiver operator curve of 0.96 and Hosmer-Lemeshow goodness-of-fit P = .16 in the validation set. Four previously published external models were tested in the entire data set. Three models had ROC curves significantly less than the Toronto PCI score, and all 4 showed significant levels of imprecision. CONCLUSIONS: The Toronto PCI mortality score is an accurate and contemporary predictive tool that permits evaluation of risk-stratified outcomes and aids counseling of patients undergoing PCI.

Decreased complication rates using the transradial compared to the transfemoral approach in percutaneous coronary intervention in the era of routine stenting and glycoprotein platelet IIb/IIIa inhibitor use: a large single-center experience.

BACKGROUND: Studies evaluating the efficacy and safety of the transradial approach for percutaneous coronary intervention (PCI) were carried out mainly before the widespread use of stents and glycoprotein (GP) IIb/IIIa inhibitors. We sought to determine the association between the choice of the vascular access site and procedural complications after PCI performed with routine stenting and GP IIb/IIIa inhibition. METHODS: The data source was a prospective registry of 13,499 consecutive cases of PCI at the University Health Network, Toronto, Canada, from April 2000 to September 2006. Logistic regression was used to calculate the probability of selection to the radial access group. Using propensity score methodology, 3,198 patients with femoral access were randomly matched to 3,198 patients with radial access based on clinical, angiographic, and procedural characteristics. Multivariable logistic regression analysis was used to identify the independent predictors of access site-related complications. Major adverse cardiac event was defined as death, myocardial infarction, abrupt vessel closure, or coronary artery bypass surgery. RESULTS: Use of the transradial approach was associated with fewer vascular access complications (1.5% vs 0.6%, P<.001) and a shorter length of hospital stay. Multivariable analysis revealed transradial access (OR 0.39, 95% CI 0.2-0.7) to be an independent predictor of lower risk, whereas primary PCI (OR 4.36, 95% CI 1.4, 13), recent myocardial infarction (OR 2.0 95% CI 1.2, 3.4), age (per 10 years increase: OR 1.37, 95% CI 1.1-1.7) and female gender (0R 2.78 95% CI 1.7, 4.6) were independent predictors of a higher risk of access site complications. CONCLUSIONS: Use of transradial access for PCI is safe and is independently associated with a reduced rate of in-hospital access site complications and reduced length of hospital stay.

Long-term outcomes after percutaneous coronary intervention of bifurcation narrowings.

The optimal approach to percutaneous coronary intervention (PCI) of bifurcation lesions remains unclear, reflecting lack of long-term follow-up and heterogeneity of lesions encountered. We evaluated the long-term outcome of patients undergoing bifurcation PCI followed in the prospective bifurcation registry at the University Health Network, Toronto, Ontario, Canada. Of 526 patients undergoing bifurcation PCI between November 2003 and March 2005, most (n = 406) were treated by main vessel stenting only (n = 266) or crush/culotte stenting (n = 140). After median follow-up of 26.5 months, major adverse cardiac events (MACEs) and Canadian Cardiovascular Society class > or =2 angina occurred in 28.5% and 22.3% of patients in these groups, respectively (p = 0.190), whereas MACE rates were 20.8% for main vessel stenting and 18.7% for crush/culotte stenting (p = 0.670). A low bifurcation angle was associated with better outcomes in the crush/culotte group but had no effect on outcome of patients treated with main vessel stenting only. Use of crush/culotte techniques independently predicted freedom from MACEs or Canadian Cardiovascular Society class > or =2 angina compared with main vessel stenting only (odds ratio 0.55, 95% confidence interval 0.32 to 0.94, p = 0.029). In conclusion, the use of crush/culotte stenting is safe, with efficacy and MACE rates being similar to main vessel stenting alone. Our observations regarding the effect of lesion characteristics such as bifurcation angle and extent of side branch disease on outcome underscore the need for randomized trials that are inclusive of patients with complex side branch disease.

Thrombocytopenia at baseline is a predictor of inhospital mortality in patients undergoing percutaneous coronary intervention.

BACKGROUND: Thrombocytopenia (TP) is a common baseline abnormality in patients undergoing percutaneous coronary intervention (PCI). Whether TP has any influence on the outcome of PCI patients is unknown. Our aim was to determine if TP at baseline impacts on inhospital mortality in patients undergoing PCI at our institution. METHODS: From April 2000 until October 2005, 11,021 PCI procedures were performed at the University Health Network in Toronto, Canada. Baseline platelet count was recorded in 10,821 (98.2%) cases. Patients with platelets <150 x 10(9)/L were assigned to the TP group (n = 639), and those with > or =150 x 10(9)/L to the normal platelet group (n = 10,182). Clinical, angiographic, procedural, and inhospital outcome data were collected prospectively. Multivariable analysis was performed using logistic regression. RESULTS: In-hospital death rate was higher in the TP group (1.9% vs 0.6%, P < .001) due to an increased mortality in TP patients undergoing urgent (3.55% vs 1.15%, P < .001) but not elective (0% vs 0.04%, P = 1.0) PCI. Major bleeding (1.7% vs 0.8%, P < .05) and gastrointestinal bleeding (1.1% vs 0.5%, P < .05) complications were greater in the TP group. Multivariate analysis demonstrated that baseline TP was an independent predictor of inhospital mortality (odds ratio 2.07 [1.1-4.1], P = .035). CONCLUSIONS: Baseline TP is an independent predictor of inhospital mortality in patients undergoing PCI for urgent indications. Thrombocytopenia should be considered an important addition to PCI risk prediction models to improve their precision and clinical applicability.

Impact of renal insufficiency on angiographic, procedural, and in-hospital outcomes following percutaneous coronary intervention.

Patients with chronic renal insufficiency (RI) have higher in-hospital mortality and major adverse cardiac event (MACE) rates after percutaneous coronary intervention (PCI). The mechanisms of this adverse course are not well understood. It was hypothesized that this worse outcome may be caused by inadequate PCI results secondary to more complex coronary anatomy in patients with RI. Baseline, procedural, and outcome variables of all PCI cases at the University Health Network are entered prospectively in the PCI Registry. All PCI cases between April 1, 2000, and October 31, 2005, excluding patients in shock, who had preprocedural creatinine clearance (CrCl) measured were included in this study (n = 10,821 of 11,023 patients). Moderate RI (CrCl <60 ml/min) was evaluated as an independent predictor of procedural outcomes, death, and MACE (defined as death, myocardial infarction, abrupt closure, or coronary artery bypass grafting). Moderate RI (CrCl <60 ml/min) independently predicted the procedural outcomes of worse residual stenosis >20% (p = 0.03), number of undeliverable stents (p = 0.003), and smallest stent diameter (p <0.001). Worst residual stenosis >20% and any undeliverable stent were significantly associated with in-hospital MACEs (odds ratio [OR] 3.97, 95% confidence interval [CI] 3.0 to 5.3, p <0.001 and OR 1.89, 95% CI 1.2 to 2.9, p = 0.002) and mortality (OR 3.82, 95% CI 2.2 to 6.7, p <0.001 and OR 3.0, 95% CI 1.6 to 5.9, p = 0.002). These risks were independent of all other measured variables. In conclusion, moderate to severe RI was a strong predictor of worse procedural results during PCI, which, in turn, were independent predictors of in-hospital MACE and mortality and independent contributors to the higher risk of in-hospital adverse events observed after PCI in patients with RI.

Predictors of long-term outcome after crush stenting of coronary bifurcation lesions: importance of the bifurcation angle.

OBJECTIVES: We hypothesized that the bifurcation angle (BA) may affect the outcome of crush stenting (CS) of bifurcation lesions and thus set out to determine the effect of the BA on outcome of patients undergoing coronary bifurcation CS. METHODS: Of 538 bifurcation PCI cases performed between November 2003 and March 2005, 133 were performed using CS (n = 56), balloon CS (n = 71), or reverse CS (n = 6). Patients were divided into low-angle and high-angle groups using the median BA as the cut point. RESULTS: The median BA was 50 degrees. High-angle patients were more likely to be women (33% vs 15%, P = .02), with a prior percutaneous coronary intervention (26% vs 12%. P = .05) and coronary artery bypass grafting (15% vs 5%, P = .05). Procedural success was 98.5% in the low-angle and 95.4% in the high-angle group (P = nonsignificant). Two high-angle patients had acute stent thrombosis, and 1 died in hospital. Four additional high-angle patients (6.1%) and 1 low-angle patient (1.5%) died (P = nonsignificant) during follow-up. Major adverse cardiac events (MACE) occurred more frequently in the high-angle group (22.7% vs 6.2%, P = .007). Bifurcation angle > or = 50 degrees (P = .004), no final kissing balloon inflation (P = .012), and creatinine clearance < 40 mL/min (P = .031) independently predicted MACE. CONCLUSIONS: Bifurcation angle > or = 50 degrees is an independent predictor of MACE after bifurcation CS, in addition to no final kissing balloon inflation and severe renal dysfunction. A high BA confers a setting of increased turbulent flow that is further exacerbated by suboptimal treatment of the crushed side-branch stent. Further study to improve outcome in this subset of patients is warranted.

Impact of renal insufficiency on outcome after contemporary percutaneous coronary intervention.

BACKGROUND: End-stage renal failure is associated with poor outcomes, including increased mortality, after percutaneous coronary intervention (PCI). The effect of milder degrees of renal insufficiency (RI) is less clear, especially with routine stenting and glycoprotein IIb/IIIa inhibitor therapy, which may be of particular benefit in patients with RI. METHODS: Clinical, angiographic, procedural, and outcome variables of 7769 consecutive patients who underwent PCI between April 2000 and July 2004 were entered into a prospective database. Inhospital mortality and morbidity were calculated according to baseline creatinine clearance. Simple and multiple logistic regression analyses were performed to determine independent predictors of mortality. RESULTS: Baseline creatinine clearance was available in 6840 patients. It was normal (> 80 mL/min) in 3474; 1670 had mild RI (61-80 mL/min), 1111 moderate RI (41-60 mL/min), and 585 severe RI (< or = 40 mL/min). Major adverse cardiac events (MACE) (death/myocardial infarction/revascularization) increased substantially with worsening renal function (2.4% vs 3.0% vs 4.8% vs 9.7%, P < .0001), as did mortality (0.3% vs 0.7% vs 1.5% vs 6.0%, P < .0001). Multiple logistic regression analysis identified moderate RI and severe RI as independent predictors of mortality (odds ratio [OR] 3.9, P < .001; OR 12.7, P < .0001, respectively) and morbidity (MACE) (OR 1.5, P < .05; OR 2.5, P < .0001, respectively). Mild RI trended to increase the risk of mortality but did not reach statistical significance as an independent predictor of inhospital death on multiple regression analysis (OR 2.1, P = .1) and did not increase the risk of MACE (OR 1.1, P = .6). CONCLUSIONS: Despite routine stenting and glycoprotein IIb/IIIa inhibitor therapy, RI remains an independent predictor of increased morbidity, and particularly mortality, after PCI. However, the adverse effect of truly mild RI on outcome is limited.

Routine use of glycoprotein IIb/IIIa inhibitor therapy is associated with an improved in-hospital outcome after percutaneous coronary intervention: Insights from a large, prospective, single-centre registry.

BACKGROUND: Clinical trials have demonstrated the benefit of glycoprotein IIb/IIIa inhibitors (GPIs) with stenting in the setting of percutaneous coronary intervention (PCI) in reducing adverse cardiac outcomes. OBJECTIVES: To assess the association between a strategy of routine GPI use and the prevention of adverse cardiac outcomes post-PCI at a large, tertiary care institution. PATIENTS AND METHODS: Patients who underwent a first PCI at the institution from April 1994 to February 2001 were divided into three cohorts: pre-GPI with selected stent use (P1), selected GPI with routine stent use (P2), and routine GPI with routine stent use (P3). A multiple logistic regression model was constructed to evaluate the different strategy periods, with the rate of in-hospital myocardial infarction, death and abrupt closure as the primary composite end point. RESULTS: The cohort comprised 7702 patients (2621, 3501 and 1580 patients in P1, P2 and P3, respectively). GPI use increased from 0% in P1 to 17.5% in P2 to 91.0% in P3. There was a significant difference in the unadjusted composite end point among the three periods (4.9%, 3.4% and 2.6%, for P1, P2 and P3, respectively; P<0.001). In the multiple regression analysis, the composite end point was significantly greater in P1 and P2 than in P3 (P1 versus P3, OR 2.61, P<0.0001; P2 versus P3, OR 1.55; P=0.0204). CONCLUSIONS: A significant reduction in adverse in-hospital clinical cardiac events was observed in association with the strategy of routine use of GPI therapy and stenting in a large, consecutive PCI cohort after adjusting for potentially confounding patient characteristics.

Impact of delays to cardiac surgery after failed angioplasty and stenting.

OBJECTIVES: This study was designed to determine the likelihood of harm in patients having additional delays before urgent coronary artery bypass graft (UCABG) surgery after percutaneous coronary intervention (PCI). BACKGROUND: Patients who have PCI at hospitals without cardiac surgery have additional delays to surgery when UCABG is indicated. METHODS: Detailed chart review was performed on all patients who had a failed PCI leading to UCABG at a large tertiary care hospital. A prespecified set of criteria (hemodynamic instability, coronary perforation with significant effusion or tamponade, or severe ischemia) was used to identify patients who would have an increased likelihood of harm with additional delays to surgery. RESULTS: From 1996 to 2000, 6,582 PCIs were performed. There were 45 patients (0.7%) identified to have UCABG. The demographic characteristics of the UCABG patients were similar to the rest of the patients in the PCI database, except for significantly more type C lesions (45.3% vs. 25.0%, p < 0.001) and more urgent cases (66.6% vs. 49.8%, p = 0.03) in patients with UCABG. Myocardial infarction occurred in eight patients (17.0%) after UCABG, with a mean peak creatine kinase of 2,445 +/- 1,212 IU/l. Death during the index hospital admission occurred in two patients. Eleven of the 45 patients (24.4%) were identified by the prespecified criteria to be at high likelihood of harm with additional delays to surgery. The absolute risk of harm is approximately one to two patients per 1,000 PCIs. CONCLUSIONS: Approximately one in four patients referred for UCABG would be placed at increased risk of harm if delays to surgery were encountered.

A 17-month evaluation of a chlorine dioxide water treatment system to control Legionella species in a hospital water supply.

OBJECTIVE: To assess the safety and efficacy of a chlorine dioxide water treatment system in controlling Legionella in a hospital water supply. DESIGN: For 17 months following installation of the system, we performed regular water cultures throughout the building, assessed chlorine dioxide and chlorite levels, and monitored metal corrosion. RESULTS: Sites that grew Legionella species decreased from 41% at baseline to 4% (P = .001). L. anisa was the only species recovered and it was found in samples of both hot and cold water. Levels of chlorine dioxide and chlorite were below Environmental Protection Agency (EPA) limits for these chemicals in potable water. Further, enhanced carbon filtration effectively removed the chemicals, even at chlorine dioxide levels of more than twice what was used to treat the water. After 9 months, corrosion of copper test strips exposed to the chlorine dioxide was not higher than that of control strips. During the evaluation period, there were no cases of nosocomial Legionella in the building with the system, whereas there was one case in another building. CONCLUSIONS: Our results indicate that operation of a chlorine dioxide system effectively removed Legionella species from a hospital water supply. Furthermore, we found that the system was safe, as levels of chlorine dioxide and chlorite were below EPA limits. The system did not appear to cause increased corrosion of copper pipes. Our results indicate that chlorine dioxide may hold promise as a solution to the problem of Legionella contamination of hospital water supplies.