Collagenase to facilitate guidewire crossing in chronic total occlusion PCI-The Total Occlusion Study in Coronary Arteries-5 (TOSCA-5) trial.

BACKGROUND: Chronic total occlusions (CTO) are common and are associated with lower percutaneous coronary intervention (PCI) success rates, often due to failure of antegrade guidewire crossing. Local, intralesional delivery of collagenase (MZ-004) may facilitate guidewire crossing in CTO. AIMS: To evaluate the effect of MZ-004 in facilitating antegrade wire crossing in CTO angioplasty. METHODS: A total of 76 patients undergoing CTO PCI were enrolled at 13 international sites: 38 in the randomized training stage (collagenase [MZ-004] 900 or 1200 µg) and 38 in the placebo-controlled stage (MZ-004 900 or 1200 µg or placebo). Patients received the MZ-004 or identical volume saline (placebo group) in a double-blind design, injected via microcatheter directly into the proximal cap of the CTO. The following day patients underwent CTO PCI using antegrade wire techniques only. RESULTS: Patients were generally similar except for a trend for higher Japanese chronic total occlusion (J-CTO) score in the MZ-004 group (MZ-004 J-CTO score 1.9 vs. 1.4, p = 0.07). There was a numerical increase in the rates of guidewire crossing in the MZ-004 groups compared to placebo (74% vs. 63%, p = 0.52). Guidewire crossing with a soft-tip guidewire (≤1.5 g tip load) was significantly higher in the MZ-004 groups (0% in placebo, 17% in 900 µg, and 29% in 1200 µg MZ-004 group, p = 0.03). Rates of the major adverse cardiovascular event were similar between groups. CONCLUSION: Local delivery of MZ-004 into coronary CTOs appears safe and may facilitate CTO crossing, particularly with softer tipped guidewires. These data support the development of a pivotal trial to further evaluate this agent.

Risk Prediction Models for Contrast-Induced Acute Kidney Injury Accompanying Cardiac Catheterization: Systematic Review and Meta-analysis.

BACKGROUND: Identification of patients at risk of contrast-induced acute kidney injury (CI-AKI) is valuable for targeted prevention strategies accompanying cardiac catheterization. METHODS: We searched MedLine and EMBASE for articles that developed or validated a clinical prediction model for CI-AKI or dialysis after angiography or percutaneous coronary intervention. Random effects meta-analysis was used to pool c-statistics of models. Heterogeneity was explored using stratified analyses and meta-regression. RESULTS: We identified 75 articles describing 74 models predicting CI-AKI, 10 predicting CI-AKI and dialysis, and 1 predicting dialysis. Sixty-three developed a new risk model whereas 20 articles reported external validation of previously developed models. Thirty models included sufficient information to obtain individual patient risk estimates; 9 using only preprocedure variables whereas 21 included preprocedural and postprocedure variables. There was heterogeneity in the discrimination of CI-AKI prediction models (median [total range] in c-statistic 0.78 [0.57-0.95]; I2 = 95.8%, Cochran Q-statistic P < 0.001). However, there was no difference in the discrimination of models using only preprocedure variables compared with models that included postprocedural variables (P = 0.868). Models predicting dialysis had good discrimination without heterogeneity (median [total range] c-statistic: 0.88 [0.87-0.89]; I2 = 0.0%, Cochran Q-statistic P = 0.981). Seven prediction models were externally validated; however, 2 of these models showed heterogeneous discriminative performance and 2 others lacked information on calibration in external cohorts. CONCLUSIONS: Three published models were identified that produced generalizable risk estimates for predicting CI-AKI. Further research is needed to evaluate the effect of their implementation in clinical care.

Randomized trial of insulin versus usual care in reducing restenosis after coronary intervention in patients with diabetes. the STent Restenosis And Metabolism (STREAM) study.

BACKGROUND: Diabetes status is an independent marker of restenosis after percutaneous coronary intervention (PCI). Previous studies suggest that metabolic abnormalities associated with diabetes increase stent restenosis by promoting intimal hyperplasia. Preclinical studies have indicated that insulin therapy reduces intimal hyperplasia. The objective of this study was to determine whether insulin-mediated glucose lowering reduces in-stent restenosis in patients with diabetes undergoing PCIs. METHODS: We conducted a prospective, randomized, multicenter, open-labeled study with blinded outcomes. Patients were randomized 1:1 to daily bedtime subcutaneous NPH insulin (Novo Nordisk) versus usual therapy with oral hypoglycemic agents. The main outcomes were change in volume of intimal hyperplasia within the stent measured by intravascular ultrasound and late lumen loss by quantitative coronary angiography at 6 months post-PCI. RESULTS: Seventy-eight patients (36 insulin, 42 usual care) were randomized. Eight patients in each group received drug-eluting stents. The insulin group achieved greater reductions in both glycosylated hemoglobin A1c (mean±S.D.) (insulin: 8.0%±1.2% to 6.7%±0.7% vs. control: 7.5%±1.2% to 7.1%±1.0 %, P=.0038) and fasting glucose (insulin: 9.3±3.8 to 5.8±1.7 vs. usual care: 8.4±2.4 to 7.7±2.0 mmol/l, P<.0001). There were no hypoglycemic events. At 6 months, there were no significant differences in either intravascular-ultrasound-determined neointimal volume (insulin: 41.2±38.9 vs. usual care: 48.4±40.2 mm(3), P=.33) or late lumen loss by angiography (insulin: 1.29±0.74 mm vs. usual care: 1.02±0.71 mm, P=.17). CONCLUSIONS: Addition of a single bedtime dose of insulin in patients with diabetes does not influence in-stent restenosis.

An early cardiac access clinic significantly improves cardiac rehabilitation participation and completion rates in low-risk ST-elevation myocardial infarction patients.

BACKGROUND: Survivors of an acute ST-elevation myocardial infarction (STEMI) remain at high risk for future cardiac events. Cardiac rehabilitation (CR) participation significantly reduces coronary artery disease (CAD) morbidity and mortality risk. Regrettably, poor utilization of CR services post STEMI is common, accentuating a critical action gap in the trajectory of CAD management. The objective of this study was to determine whether integration of an early cardiac access clinic (ECAC), held within 4-14 days of hospital discharge, could improve CR utilization rates following an STEMI. METHODS: Between January 2008 and July 2009, 245 consecutively admitted STEMI patients (19.6% female) deemed low risk following early re-establishment of coronary blood flow, were assigned to the ECAC model. An historic comparison group (n=224) was identified based on all STEMI patient admissions at the same tertiary care facility during the 2007 calendar year that met ECAC eligibility criteria. The primary outcomes were rates of CR referral, orientation attendance, program participation, and completion. RESULTS: The ECAC cohort had significantly higher rates of CR referral (100% vs 55.8%, P < 0.0001), orientation attendance (96.3 vs 37.1%, P < 0.0001), program participation (87.8% vs 33.5%, P < 0.0001), and completion (71.4% vs 29.9%, P < 0.001) compared to the matched historical comparison group. CONCLUSIONS: The utilization of the ECAC model resulted in an unprecedented (∼3-fold) increase in the number of post-STEMI patients participating in CR. Given the unequivocal mortality and morbidity benefits of CR, adoption of the ECAC model has important clinical and economic relevance.

Prognostic implications of C-reactive protein and troponin following percutaneous coronary intervention.

BACKGROUND: C-reactive protein (CRP), a marker of inflammation, plays a role in the pathophysiology of atherosclerotic events. The relationship between CRP levels and myocardial necrosis assessed by troponin T (TnT) in patients undergoing percutaneous coronary intervention (PCI) has not been established. In addition, the long-term significance of TnT rise following PCI is not clear. OBJECTIVES: To examine the relationship between CRP and the rise in TnT levels, and evaluate the long-term prognostic implications of TnT rise following PCI. METHODS: A total of 1208 patients underwent successful nonemergent PCI. Baseline demographic characteristics, CRP and TnT levels were prospectively collected before and 12 h to 18 h following PCI. Long-term follow-up data over two years were available. RESULTS: Among the patients studied (mean age 62 years), 64% presented with acute coronary syndrome. A PCI procedure was associated with a significant increase in TnT levels (higher than 0.1 microg/L) in 238 patients (20%). Multivariate logistic regression identified presentation with acute coronary syndrome or myocardial infarction, no statin use at the time of the procedure, increased CRP and increasing length of stent as independent predictors of TnT rise following PCI. Periprocedural TnT rise was not associated with adverse events in follow-up examinations (OR 1.09, 95% CI 0.73 to 1.65). CONCLUSIONS: Myocardial necrosis commonly occurred in otherwise successful PCI and was particularly prevalent in the proinflammatory milieu of a recent myocardial infarction. This response was blunted with statin therapy. However, there was no long-term adverse sequelae of these troponin rises following otherwise uncomplicated PCI.

Obesity is associated with impaired human coronary endothelial function.

BACKGROUND: Obesity is an independent risk factor for cardiovascular disease. Endothelial dysfunction assessed in the peripheral circulation is associated with obesity, however, little is known if this association also exists in the coronary circulation. METHODS: Stable patients with coronary artery disease were evaluated. Baseline characteristics were evaluated, including assessment of body mass index [(BMI), kg/m(2)]. Coronary diameter (quantitative coronary angiography) and blood flow (0.014 in. Doppler Flo-wire) were measured at baseline and in response to intracoronary acetylcholine (10(-7) and 10(-6) M) to evaluate endothelial dependent effects with endothelial independent effects evaluated in response to intracoronary nitroglycerin and adenosine. The cohort was divided into tertiles around BMI values, i.e. normal weight (BMI < 25), overweight (BMI 25-29.9) and obese (BMI ≥ 30) groups. RESULTS: 83 patients were evaluated, with 20 patients in the normal weight (BMI 22.6 ± 0.3 kg/m(2)), 40 subjects in the overweight (BMI 27.3 ± 0.2 kg/m(2)) and 23 in the obese (BMI 34.3 ± 0.3 kg/m(2)) groups. A significant difference was seen in the primary endpoint of Ach mediated % change in coronary blood flow between the normal (101 ± 28%) and the obese (37 ± 15%) groups (p = 0.04). No significant difference was observed in epicardial constrictor response to acetylcholine across these three groups of patients. CONCLUSIONS: In a cohort of subjects with coronary artery disease, patients with a high BMI had associated impaired microvascular coronary endothelial dependent function.

Effects of tetrahydrobiopterin on coronary vascular reactivity in atherosclerotic human coronary arteries.

OBJECTIVES: Reduced nitric oxide (NO) bioavailability is a key mechanism in the development of endothelial dysfunction. The NO synthase cofactor, tetrahydrobiopterin (BH4), increases NO availability, yet its effect in the human coronary circulation, particularly following PCI, remains uncertain. This study was designed to evaluate the effects of intracoronary BH4 in human coronary arteries with non-critical coronary artery disease or following percutaneous coronary intervention (PCI). METHODS: The study group consisted of 57 stable patients, 10 of which were controls. Active drug was administered in 47 patients, with either de novo non-critical coronary disease (non-stent group; n=25) or following PCI (stent group; n=22). Coronary blood flow (CBF) was measured (0.014-inch Doppler flow wire) in each of these groups in response to sequential intracoronary infusions of acetylcholine (Ach, 10(-7) & 10(-6) M), BH4 (250 microg/min & 500 microg/min) and a co-infusion of BH4 (500 microg/min) and Ach (10(-7) & 10(-6) M). The primary endpoint evaluated the % change in CBF to Ach compared to co-infusion of Ach and BH4. RESULTS: Mean age was 60+/-10 years (M 45:F 12). Regarding the primary hypothesis, no difference was observed between Ach response compared to co-infusion of BH4 and Ach in the % change in CBF in either the non-stent group (Ach 97+/-122%, Ach/BH4 87+/-95%) or the stent group (Ach 77+/-105%, Ach/BH4 55+/-97%). CONCLUSIONS: In native non-critical coronary artery disease or following PCI, coronary microvascular endothelial function is not improved by co-administration of Ach and BH4.

Registry data evaluating the effectiveness of drug-eluting stents for the treatment of symptomatic in-stent restenosis.

BACKGROUND: In this new-era of drug-eluting stents (DES) the impact of symptomatic in-stent restenosis (ISR) is diminishing. However, world wide bare-metal stents remain widely used and therefore, it is imperative to establish a simple and effective form of treatment. The objective of this registry database was to evaluate the 'real-world' effectiveness of DES for the treatment of symptomatic bare-metal stent ISR. METHODS: All patients presenting with symptomatic ISR were evaluated between February 2003 and February 2005. Patients had 9-month angiographic follow-up with primary endpoint evaluation of binary restenosis (>50%). Secondary endpoints included in-segment late loss, target lesion revascularization (TLR) and the difference in late loss between sirolimus (n=23) and paciltaxel (n=36) eluting stents. RESULTS: Fifty eight patients with fifty nine ISR lesions were evaluated, 36% of patients had diabetes mellitus. All procedures were performed safely with no adverse peri-procedural events documented. At 9-month follow-up the median in-segment late loss was 0.24 mm (IQR 0.1, 0.53), with a binary restenosis rate of 17%. At long-term follow-up greater than 1 year, the incidence of TLR was 10%. No difference in the angiographic parameter of in-segment late loss was seen between the sirolimus and paclitaxel-eluting stents. CONCLUSIONS: In this cohort of patients with long-term angiographic and clinical follow-up, DES is an effective and safe treatment for symptomatic bare-metal stent ISR.

Effect of percutaneous coronary intervention of nonacute total coronary artery occlusions on QT dispersion.

BACKGROUND: Myocardial ischemia is one of several potential causes of increased QT dispersion (QTd) in patients with nonacute total coronary artery occlusions (TCOs). We sought to assess the effect of percutaneous revascularization (PCI) of TCO on QTd and the relationship between QTd and long-term vessel patency. METHODS: Seventy patients enrolled in the TOSCA were analyzed. Patients were undergoing PCI of a TCO > 72 hours' duration. Two independent reviewers measured QTd from electrocardiograms done immediately before PCI (PRE), 12 to 18 hours after PCI (POST), and then at 6 months (6M). Follow-up angiography was performed at 6 months. RESULTS: Mean QTd decreased from PRE (77 +/- 29 milliseconds) to POST (66 +/- 26 milliseconds, P < .001) and 6M (65 +/- 25 milliseconds, P < .001). Patients with the same or longer QTd at 6 months compared with POST (POST < or = 6M) had significantly higher risk of failed target-vessel patency (odds ratio 10.3, 95% CI 1.24-84.8) than patients with QTd reduction at 6M versus POST values. CONCLUSION: Revascularization of TCO resulted in a decrease in QTd, which was sustained at 6M. This suggests that PCI to a TCO has a beneficial effect on stabilization of the underlying ischemic substrate. Furthermore, absence of QTd reduction at 6M versus POST was associated with increased risk of failed target-vessel patency.

A randomized pilot study of dalteparin versus unfractionated heparin during percutaneous coronary interventions.

BACKGROUND: Direct comparison of low-molecular-weight heparin, dalteparin, with unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) is limited. This study examined the relative effects of dalteparin and UFH on coagulation and angiographic and clinical indices during PCI. METHODS: This was a double-blind randomized study, stratified by planned glycoprotein IIb/IIIa inhibitor use. Both UFH and dalteparin were administered as an intra-arterial bolus immediately before PCI. RESULTS: All randomized patients received the assigned study drug and underwent PCI. Mean activated clotting time levels were 344 seconds for UFH and 234 seconds for dalteparin (P < .0001). Anti-factor Xa levels were higher for dalteparin at 30 minutes (UFH 1.3 IU/mL vs dalteparin 1.7 IU/mL, P = .005)) and at 4 hours (UFH 0.27 IU/mL vs dalteparin 0.69 IU/mL, P < .0001). Angiographic success was > 90% in both groups, and angiographic complications were similar (UFH 2.5% vs dalteparin 3.8%). The composite of death, myocardial infarction, target vessel revascularization, or bailout glycoprotein IIb/IIIa at hospital discharge was 13.7% in the UFH group and 13.1% in the dalteparin group (P = not significant). There were 2 major bleedings requiring transfusion, both occurring in the UFH group. CONCLUSIONS: This study suggests that a single intra-arterial bolus of low-molecular-weight heparin without monitoring is feasible and warrants further investigation as an alternative to UFH during PCI.

Large and small vessel vasoconstriction following coronary artery stenting. Effect of intra coronary nitroglycerine and relation to LDL cholesterol.

UNLABELLED: Percutaneous coronary intervention (PCI) with stent placement induces epicardial coronary vasoconstriction, which is resolved by intracoronary (IC) nitroglycerine (NTG). The effect of stenting on microvascular coronary circulation and coronary blood flow (CBF) is less well established, and the effect of NTG on CBF following stenting is unknown. We examined the time course, extent, and influence of NTG, on PCI induced coronary vasoconstriction. Secondarily we also did an explorative analysis to evaluate the effect of increased levels of low density lipoprotein cholesterol (LDL-Cholesterol) on CBF after stenting. METHODS: Single vessel PCI stent was performed in 19 patients (age 62+/-10 years). Immediately after PCI, a 0.014 Doppler flow-wire was positioned distal to the stent, and IC NTG 0.2 mg was given. Quantitative coronary angiography (QCA) and CBF measurements were taken at baseline, and at 10, 20 and 30 min following PCI. Further IC NTG 200 mug was given after the measurement at 30 min, and the measurements were repeated at 31 and 33 min. Coronary flow velocity reserve (CFVR) was measured with adenosine IC bolus. RESULTS: Compared to baseline, there were significant reductions in CBF (24.5+/-18.3%), (35+/-30 vs. 28+/-25 ml/min, p=0.001) and coronary arterial diameter (5.1+/-5.4%) (2.63+/-0.54 vs. 2.50 mm+/-0.53, p=0.008) within 30 min following PCI. Subsequent IC NTG reversed both small (28+/-25 vs. 44+/-30 ml/min, p<0.001) and large (2.50+/-0.53 vs. 2.80+/-0.59 mm, p=0.001) vessel PCI induced vasoconstriction. LDL-cholesterol was significantly correlated to the percent reduction of blood-flow within 30 min (r=0.515, p=0.024, n=19) and to the maximal CBF after NTG (r=0.520, p=0.022, n=19). CONCLUSION: Following PCI, both large and small vessel vasoconstriction are seen as manifest by a reduction in coronary conduit vessel diameter and in CBF. These effects are reversed by NTG. Serum levels of LDL are modestly related to the reduction of CBF and to the degree of NTG induced vasodilatation of coronary micro-vasculature.

Relation of Basal coronary nitric oxide activity to the burden of atherosclerosis.

Coronary disease or its risk factors has been reported to attenuate basal nitric oxide (NO) activity. Intravascular ultrasound was used in the present study to better understand this relation. Basal and stimulated NO activities were assessed in 53 stable subjects. Coronary diameter and velocity (0.014-inch Doppler wire) were measured at baseline and after intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl-l-arginine, acetylcholine (10(-6) M), nitroglycerin (200 microg), and adenosine (24 microg). Intimal thickening was quantified with intravascular ultrasound. N(G)-monomethyl-l-arginine resulted in significant decreases in coronary blood flow (-14 +/- 48%), proximal coronary diameter (-10 +/- 18%), and distal coronary diameter (-10 +/- 9%, all p values <0.0001). Basal NO activity was unrelated to the presence of coronary disease as assessed by angiography and the burden of atherosclerosis as assessed by intravascular ultrasound. Conversely, stimulated NO activity correlated inversely with burden of coronary atherosclerosis (p <0.05). Basal NO activity is relatively preserved in patients who have moderate coronary disease and is not related to the degree of atherosclerosis as assessed by intravascular ultrasound. This is in contradistinction to the impairment of stimulated NO activity in the coronary circulation that characterizes atherosclerosis.

Randomized, blinded trial comparing fondaparinux with unfractionated heparin in patients undergoing contemporary percutaneous coronary intervention: Arixtra Study in Percutaneous Coronary Intervention: a Randomized Evaluation (ASPIRE) Pilot Trial.

BACKGROUND: Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to standard therapies for the prevention of venous thrombosis. We performed a randomized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention (PCI) setting. METHODS AND RESULTS: A total of 350 patients undergoing elective or urgent PCI were randomized in a blinded manner to receive unfractionated heparin (UFH), 2.5 mg fondaparinux IV, or 5.0 mg fondaparinux IV. Randomization was stratified for planned or no planned use of glycoprotein (GP) IIb/IIIa antagonists. The primary safety outcome was total bleeding, which was a combination of major and minor bleeding events. The incidence of total bleeding was 7.7% in the UFH group and 6.4% in the combined fondaparinux groups (hazard ratio, 0.81; 95% confidence interval, 0.35 to 1.84; P=0.61). Bleeding was less common in the 2.5-mg fondaparinux group compared with the 5-mg fondaparinux group (3.4% versus 9.6%, P=0.06). The composite efficacy outcome of all-cause mortality, myocardial infarction, urgent revascularization, or need for a bailout GPIIb/IIIa antagonist was 6.0% in the UFH group and 6.0% in the fondaparinux group, with no significant difference in efficacy among the fondaparinux doses compared with UFH. Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation, as measured by prothrombin fragment F1.2 (P=0.02). CONCLUSIONS: In this pilot study of patients undergoing contemporary PCI, factor Xa inhibition with the synthetic anticoagulant fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes. These data form the basis for further evaluation of fondaparinux in arterial thrombosis.

Coronary flow velocity reserve does not correlate with TIMI frame count in patients undergoing non-emergency percutaneous coronary intervention.

OBJECTIVES: The purpose of this research was to compare the Thrombolysis In Myocardial Infarction (TIMI) frame count (CTFC) with coronary flow velocity reserve (CFVR) in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: The relationship between CTFC and CFVR has not been adequately assessed in patients with coronary artery disease. METHODS: We studied 62 patients who underwent successful non-emergent PCI. All patients had Doppler evaluation of CFVR, CTFC, and quantitative coronary angiography. In an additional 17 patients, a frame count reserve was calculated as baseline CTFC/CTFC at peak hyperemia, induced by intracoronary adenosine after PCI. RESULTS: The CTFC decreased from 27 +/- 13 to 18 +/- 8, and CFVR increased from 1.5 +/- 0.4 to 2.6 +/- 0.7 (both p < 0.0001). The pre-PCI CTFC and the CFVR were closely related to minimal lumen diameter (p < 0.0001). After PCI, there was no correlation between CFVR and CTFC. In addition, no relationship was observed between CFVR and the frame count reserve. CONCLUSIONS: There was no significant correlation between CFVR and CTFC in patients undergoing coronary intervention. The relative utility of these measures in predicting outcomes in this setting requires further evaluation, but CTFC (or frame count reserve) does not appear to be an adequate surrogate measure of Doppler-derived CFVR.

Incidence, predictors, and clinical significance of troponin-I elevation without creatine kinase elevation following percutaneous coronary interventions.

The objectives of this study were to investigate the incidence, predictors, and clinical significance of isolated postprocedural troponin-I elevations in a consecutive series of patients who underwent percutaneous coronary intervention. We observed, in a series of 1,128 patients, that isolated troponin-I elevations without concomitant creatine kinase elevations occurred in 17% of patients after percutaneous coronary intervention, and that even troponin-I elevations 5 times above the upper limit of normal did not predict events after hospital discharge.

The risks of waiting for cardiac catheterization: a prospective study.

BACKGROUND: Few large, systematic, prospective studies have documented the characteristics and clinical outcomes of patients awaiting cardiac catheterization and the delays that they experience. The primary objective of this study was to quantify the waiting times, morbidity and mortality of patients waiting for catheterization. A secondary objective was to identify predictors of cardiac events that occur while patients are waiting. METHODS: A computerized, prospective, central waiting list registry was developed at a regional centre in Hamilton, Ont., serving 2.2 million people in southern Ontario. Between Apr. 1, 1998, and Mar. 31, 2000, 8030 consecutive patients (4725 outpatients and 3305 inpatients) were referred for cardiac catheterization. Major cardiac outcomes while on the waiting list (death, myocardial infarction and congestive heart failure) were documented prospectively and related to requested versus actual waiting time. RESULTS: Most of the referrals (7345 [91.5%]) were for a primary diagnosis of suspected coronary artery disease. The median waiting time was 6 (interquartile range [IQR] 4) days for inpatients and 60 (IQR 68) days for outpatients. Actual waiting times correlated with the waiting times requested by the referring physicians. However, only 37% of the procedures overall were completed within the requested waiting time. Of the 8030 patients, 50 (0.6%) died, 32 (0.4%) had a myocardial infarction and 41 (0.5%) experienced congestive heart failure. Overall, 109 patients (1.4%) had a major cardiac event, namely, death, myocardial infarction or congestive heart failure. These events occurred over a median wait of 27 days (2 days for inpatients and 35 days for outpatients), and over half (57%) occurred within the waiting time requested by the referring physician. In the multivariate analysis, predictors of the composite of death, myocardial infarction or congestive heart failure were increasing age (relative risk [RR] 2.39, 95% confidence interval [CI] 1.52-3.75) and New York Heart Association class III/IV symptoms (RR 2.86, 95% CI 1.11-7.33) in inpatients, and increasing age (RR 1.36, 95% CI 1.12-1.66), aortic stenosis (RR 3.70, 95% CI 1.93-7.08) and left ventricular ejection fraction less than 35% (RR 4.35, 95% CI 2.48-7.61) in outpatients. INTERPRETATION: Patients awaiting cardiac catheterization may experience major adverse events, such as death, myocardial infarction and congestive heart failure, which may be preventable. Our findings provide a benchmark by which to measure the effect of increased capacity and prioritization schemes that allow earlier access for patients at higher risk, such as those with aortic stenosis and reduced left ventricular function.