Analysis of Mitochondrial Proteins in the Surviving Myocardium after Ischemia Identifies Mitochondrial Pyruvate Carrier Expression as Possible Mediator of Tissue Viability.

The endogenous mechanisms contributing to tissue survival following myocardial infarction are not fully understood. We investigated the alterations in the mitochondrial proteome after ischemia-reperfusion (I/R) and its possible implications on cell survival. Mitochondrial proteomic analysis of cardiac tissue from an in vivo porcine I/R model found that surviving tissue in the peri-infarct border zone showed increased expression of several proteins. Notably, these included subunits of the mitochondrial pyruvate carrier (MPC), namely MPC1 and MPC2. Western blot, immunohistochemistry, and mRNA analysis corroborated the elevated expression of MPC in the surviving tissue. Furthermore, MPC1 and MPC2 protein levels were found to be markedly elevated in the myocardium of ischemic cardiomyopathy patients. These findings led to the hypothesis that increased MPC expression is cardioprotective due to enhancement of mitochondrial pyruvate uptake in the energy-starved heart following I/R. To test this, isolated mouse hearts perfused with a modified Krebs buffer (containing glucose, pyruvate, and octanoate as metabolic substrates) were subjected to I/R with or without the MPC transport inhibitor UK5099. UK5099 increased myocardial infarction and attenuated post-ischemic recovery of left ventricular end-diastolic pressure. However, aerobically perfused control hearts that were exposed to UK5099 did not modulate contractile function, although pyruvate uptake was blocked as evidenced by increased cytosolic lactate and pyruvate levels. Our findings indicate that increased expression of MPC leads to enhanced uptake and utilization of pyruvate during I/R. We propose this as a putative endogenous mechanism that promotes myocardial survival to limit infarct size.

Proteomics analysis of cardiac extracellular matrix remodeling in a porcine model of ischemia/reperfusion injury.

BACKGROUND: After myocardial ischemia, extracellular matrix (ECM) deposition occurs at the site of the focal injury and at the border region. METHODS AND RESULTS: We have applied a novel proteomic method for the analysis of ECM in cardiovascular tissues to a porcine model of ischemia/reperfusion injury. ECM proteins were sequentially extracted and identified by liquid chromatography tandem mass spectrometry. For the first time, ECM proteins such as cartilage intermediate layer protein 1, matrilin-4, extracellular adipocyte enhancer binding protein 1, collagen α-1(XIV), and several members of the small leucine-rich proteoglycan family, including asporin and prolargin, were shown to contribute to cardiac remodeling. A comparison in 2 distinct cardiac regions (the focal injury in the left ventricle and the border region close to the occluded coronary artery) revealed a discordant regulation of protein and mRNA levels; although gene expression for selected ECM proteins was similar in both regions, the corresponding protein levels were much higher in the focal lesion. Further analysis based on >100 ECM proteins delineated a signature of early- and late-stage cardiac remodeling with transforming growth factor-ß1 signaling at the center of the interaction network. Finally, novel cardiac ECM proteins identified by proteomics were validated in human left ventricular tissue acquired from ischemic cardiomyopathy patients at cardiac transplantation. CONCLUSION: Our findings reveal a biosignature of early- and late-stage ECM remodeling after myocardial ischemia/reperfusion injury, which may have clinical utility as a prognostic marker and modifiable target for drug discovery.

Safety and efficacy of femoral vascular closure devices in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: The use of vascular closure devices (VCDs) for the reduction of access site complications following percutaneous coronary intervention (PCI) remains controversial. Patients undergoing primary PCI for acute ST-segment elevation myocardial infarction (STEMI) are at high risk of femoral artery complications. A lack of information exists regarding the use of VCDs in this group of patients because they have been routinely excluded from randomized trials. This study sought to evaluate the safety and efficacy of the routine use of VCDs after primary PCI. METHODS: A total of 558 consecutive patients undergoing primary PCI for STEMI via femoral route were studied for in-hospital outcomes through a prospective registry from January 2003 to December 2008. The primary end point was the presence of major vascular complication (MVC) defined as a composite of fatal access site bleeding, access site complication requiring interventional or surgical correction, or access site bleeding with ≥3 g/dL drop in hemoglobin or requiring blood transfusion. RESULTS: Of the total patients, 464 (83.2%) received a VCD; and manual compression was used in 94 patients (16.8%). Major vascular complication occurred in 5.2% of patients. The risk of MVC was significantly lower with VCDs compared with manual compression (4.3% vs 9.6%, P = .036). Multivariable logistic regression analysis determined that VCD use remained an independent predictor of lower rate of MVC (odds ratio 0.38, 95% CI 0.17-0.91). CONCLUSIONS: The use of VCDs in patients undergoing primary PCI for STEMI is safe and is associated with lower rates of MVC compared with manual compression.

Economic evaluation of complete revascularization versus stress echocardiography-guided revascularization in the STEACS with multivessel disease.

INTRODUCTION AND OBJECTIVES: Economic studies may help decision making in the management of multivessel disease in the setting of myocardial infarction. We sought to perform an economic evaluation of CROSS-AMI (Complete Revascularization or Stress Echocardiography in Patients With Multivessel Disease and ST-Segment Elevation Acute Myocardial Infarction) randomized clinical trial. METHODS: We performed a cost minimization analysis for the strategies (complete angiographic revascularization [ComR] and selective stress echocardiography-guided revascularization [SelR]) compared in the CROSS-AMI clinical trial (N=306), attributable the initial hospitalization and readmissions during the first year of follow-up, using current rates for health services provided by our health system. RESULTS: The index hospitalization costs were higher in the ComR group than in SelR arm (19 657.9±6236.8 € vs 14 038.7±4958.5 €; P <.001). There were no differences in the costs of the first year of follow-up rehospitalizations between both groups for (ComR 2423.5±4568.0 vs SelR 2653.9±5709.1; P=.697). Total cost was 22 081.3±7505.6 for the ComR arm and 16 692.6±7669.9 for the SelR group (P <.001). CONCLUSIONS: In the CROSS-AMI trial, the initial extra economic costs of the ComR versus SelR were not offset by significant savings during follow-up. SelR seems to be more efficient than ComR in patients with ST-segment elevation acute coronary syndrome and multivessel disease treated by emergent angioplasty. Study registred at ClinicalTrial.gov (Identifier: NCT01179126).

Angiographically Guided Complete Revascularization Versus Selective Stress Echocardiography-Guided Revascularization in Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Disease: The CROSS-AMI Randomized Clinical Trial.

BACKGROUND: Recent trials suggest that complete revascularization in patients with acute ST-segment-elevation myocardial infarction and multivessel disease is associated with better outcomes than infarct-related artery (IRA)-only revascularization. There are different methods to select non-IRA lesions for revascularization procedures. We assessed the clinical outcomes of complete angiographically guided revascularization versus stress echocardiography-guided revascularization in patients with ST-segment-elevation myocardial infarction. METHODS: We performed a randomized clinical trial in patients with multivessel disease who underwent a successful percutaneous coronary intervention of the IRA to test differences in prognosis (composite end point included cardiovascular mortality, nonfatal reinfarction, coronary revascularization, and readmission for heart failure after 12 months of follow-up) between complete angiographically guided revascularization (n=154) or stress echocardiography-guided revascularization (n=152) of the non-IRA lesions in an elective procedure before hospital discharge. RESULTS: The trial was prematurely stopped after the inclusion of 77% of the planned study population. As many as 152 (99%) patients in the complete revascularization group and 44 (29%) patients in the selective revascularization group required a percutaneous coronary intervention procedure of a non-IRA lesion before discharge. The primary end point occurred in 21 (14%) patients of the stress echocardiography-guided revascularization group and 22 (14%) patients of the complete angiographically guided revascularization group (hazard ratio, 0.95; 95% CI, 0.52-1.72; P=0.85). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction and multivessel disease, stress echocardiography-guided revascularization may not be significantly different to complete angiographically guided revascularization, thereby reducing the need for elective revascularization before hospital discharge. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01179126.

European registry on patients with ST-elevation myocardial infarction transferred for mechanical reperfusion with a special focus on early administration of abciximab -- EUROTRANSFER Registry.

BACKGROUND: Abciximab is established as adjunct to primary percutaneous coronary intervention (PCI). Based on some smaller studies, ST-segment elevation myocardial infarction (STEMI) networks in various European countries have adopted the start of abciximab before transfer to the catheterization laboratory (cathlab) hospital as part of their routine treatment options. Although a recently published study did not reveal improved clinical outcome when starting abciximab before the cathlab, a potential benefit from such early administration, in particular in the setting of transfer networks, remains unclear and has been the subject of debate. METHODS: Data of consecutive patients with STEMI transferred for primary PCI in hospital/ambulance-feeded STEMI networks treated between November 2005 and January 2007 at 15 PCI centers from 7 European countries were collected in the web-based EUROTRANSFER Registry. RESULTS: Data from a total of 1,650 patients were collected. Abciximab was administered to 1086 patients (66%), of whom 727 received early abciximab (EA group: abciximab started before admission to cathlab, at least 30 minutes before balloon). Another 359 patients received late abciximab (LA group: periprocedural administration of abciximab in the cathlab). Preprocedural TIMI 3 flow was observed in 17.7% of patients with EA and in 8.9% in the LA group (P < .0001). Thirty-day mortality was 3.9% in the EA group versus 7.5% with LA (OR 0.49, 95% CI 0.29-0.85, P = .011), and composite 30-day outcome including death, repeated myocardial infarction, and urgent revascularization was present in 5.5% and 10.3%, respectively (OR 0.51, 95% CI 0.32-0.81, P = .004). These differences remain statistically significant in favor of early abciximab after accounting and adjustment for differences between the groups by means of a multivariate regression model and propensity score. CONCLUSIONS: Patients in STEMI networks transferred for primary PCI who have received abciximab before transfer rather than in the cathlab had more patent arteries before PCI and showed lower rates for death and the composite clinical outcome at 30-day follow-up.

Late thrombosis of paclitaxel-eluting stents: long-term incidence, clinical consequences, and risk factors in a cohort of 604 patients.

BACKGROUND: Late thrombosis is the major safety concern of drug-eluting stents, but its incidence in common clinical practice remains controversial to date, especially beyond the first year after stent implantation. We sought to investigate the incidence, clinical consequences, and risk factors of late thrombosis after drug-eluting stent implantation. METHODS: Consecutive patients (N = 604) who received > or = 1 paclitaxel-eluting stent(s) (PES) between June 2003 and February 2005 at our institution were enrolled. Clinical characteristics and major outcomes were reviewed to detect cases and predictors of late and very late definite PES thrombosis (LDT) of PES, as currently defined by the Academic Research Council. RESULTS: During long-term follow-up (median 34.3 months, IQR 8.6), 17 cases of LDT were noted (cumulative incidence 2.8%, 95% CI 1.7%-4.5%). Most of LDT were very late thromboses (14 cases, 82%). Late and very late definite PES thrombosis appeared at a steady rate (incidence density 1.1% patient-years). Late and very late definite PES thrombosis was related to a high risk of all-cause death (HR 3.2, 95% CI 1.3-7.9) and cardiac death (HR 6.0, 95% CI 2.3-15.6). Withdrawal of antiplatelet therapy, left ventricular ejection fraction, and average stent diameter per patient were independent predictors of LDT in multivariate analysis. CONCLUSIONS: Late and very late definite PES thrombosis may be more frequent in a real setting than anticipated by initial experimental and observational studies but is keeping with more recent scientific evidence. It seems to occur at a constant rate during long-term follow-up and is associated with a high risk of overall and cardiac death.

Long-term prognostic value of mitral regurgitation in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

The presence of mitral regurgitation (MR) is associated with an impaired prognosis in patients with ischemic heart disease. However, data with regard to the impact of this condition in patients with ST-segment elevation myocardial infarction (STEMI) treated by means of primary percutaneous coronary intervention (PPCI) are lacking. Our aim was to assess the effect of MR in the long-term prognosis of patients with STEMI after PPCI. We analyzed a prospective registry of 1,868 patients (mean age 62 ± 13 years, 79.9% men) with STEMI treated by PPCI in our center from January 2006 to December 2010. Our primary outcome was the composite end point of all-cause mortality or admission due to heart failure during follow-up. After exclusions, 1,036 patients remained for the final analysis. Moderate or severe MR was detected in 119 patients (11.5%). Those with more severe MR were more frequently women (p <0.001), older (p <0.001), and with lower ejection fraction (p <0.001). After a median follow-up of 2.8 years (1.7 to 4.3), a total of 139 patients (13.4%) experienced our primary end point. There was an association between the unfavorable combined event and the degree of MR (p <0.001). After adjustment for relevant confounders, moderate or severe MR remained as an independent predictor of the combined primary end point (adjusted hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.57 to 6.27) and each event separately (adjusted HR death 3.1, 95% CI 1.34 to 7.2; adjusted HR heart failure 3.3, 95% CI 1.16 to 9.4). In conclusion, moderate or severe MR detected early with echocardiography was independently associated with a worse long-term prognosis in patients with STEMI treated with PPCI.

Radial vs femoral access after percutaneous coronary intervention for ST-segment elevation myocardial infarction. Thirty-day and one-year mortality results.

INTRODUCTION AND OBJECTIVES: Little attention has been given to the effect of vascular access site on mortality, while an increasing body of evidence is showing that radial access has much more benefit than femoral access for ST-segment elevation myocardial infarction patients. We aimed to assess the influence of vascular access site on mortality at 30 days and at 1 year in ST-segment elevation myocardial infarction patients. METHODS: We included all patients with ST-segment elevation myocardial infarction who had undergone primary angioplasty at 2 Galician hospitals between 2008 and 2010. We performed 2 multivariate regression models for each endpoint (30-day and 1-year mortality). The only difference between these models was the inclusion or not of the vascular access site (femoral vs radial). For each of the 4 models we calculated the Hosmer-Lemeshow test and the C-index. We also tested the interaction between hemodynamic instability and vascular access. RESULTS: We included 1461 patients with a mean age of 64. Of these patients, 86% had radial access and 7.4% had hemodynamic instability. All-cause mortality was 6.8% (100/1461) at 30 days and 9.3% (136/1461) at 1 year. Vascular access site follows hemodynamic instability and age in terms of effect on mortality risk, with an odds ratio of 5.20 (95% confidence interval, 2.80-9.66) for 30-day mortality. A similar effect occurs for 1-year mortality. The C-index slightly improves (without achieving statistical significance) with the inclusion of the vascular access site. CONCLUSIONS: Vascular access site should be taken into account when predicting mortality after a primary percutaneous coronary intervention.

Long-term prognostic benefit of field triage and direct transfer of patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

Direct transfer (DT) to the catheterization laboratory has been demonstrated to reduce delays in primary percutaneous coronary intervention (PPCI). However, data with regard to its effect on long-term mortality are sparse. The aim of this study was to investigate the effect of DT on long-term mortality in patients with ST-segment elevation myocardial infarctions treated with PPCI. A cohort study was conducted of 1,859 patients (mean age 63.1 ± 13 years, 80.2% men) who underwent PPCI from May 2005 to December 2010. From the whole series, 425 patients (23%) were admitted by DT and 1,434 (77%) by emergency departments. DT patients were younger (mean age 61 ± 12 vs 64 ± 12 years, p = 0.017), were more frequently men (86% vs 76%, p = 0.001), and had a higher proportion of abciximab use (77% vs 64%, p <0.0001). The DT group had a shorter median contact-to-balloon time (105 vs 122 minutes, p <0.0001) and a shorter time to treatment (185 vs 255 minutes, p <0.0001) compared with the emergency department group. Thirty-day and long-term mortality (median follow-up 2.4 years, interquartile range 1.6 to 3.2) were lower in the DT group (3% vs 6%, p = 0.049, and 9.4% vs 14.4%, p = 0.008, respectively). An adjusted Cox regression analysis proved that the DT group had an improved prognosis during follow-up (hazard ratio 0.71, 95% confidence interval 0.50 to 0.99). In conclusion, DT of patients with ST-segment elevation myocardial infarctions for PPCI was associated with fewer delays and improved survival. This benefit was maintained after long follow-up. This strategy should be emphasized in all networks of ST-segment elevation myocardial infarction care.

Comparison of the prognostic predictive value of the TIMI, PAMI, CADILLAC, and GRACE risk scores in STEACS undergoing primary or rescue PCI.

INTRODUCTION AND OBJECTIVES: We sought to compare the predictive value of the Thrombolysis In Myocardial Infarction (TIMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC), Primary Angioplasty in Myocardial Infarction (PAMI), and Global Registry for Acute Coronary Events (GRACE) scores for the outcome of ST-segment elevation acute coronary syndrome undergoing urgent percutaneous coronary intervention. METHODS: We performed a retrospective analysis of a cohort composed of all consecutive patients with ST-segment elevation acute coronary syndrome treated by urgent percutaneous coronary intervention between 2006 and 2010 (n=1503). TIMI, PAMI, CADILLAC, and GRACE risk scores were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for death, reinfarction, and target-vessel revascularization at 30 days and 1 year, using the C statistic, which was obtained by means of logistic regression and ROC curves. RESULTS: The TIMI, PAMI, CADILLAC and GRACE showed an excellent predictive value for 30-day and 1-year mortality (C statistic range, 0.8-0.9), with superiority of the TIMI, CADILLAC, and GRACE risk models. The performance of these 4 scores was poor for both reinfarction and target-vessel revascularization (C statistic, 0.5-0.6). CONCLUSIONS: The TIMI, PAMI, CADILLAC, and GRACE scores provide excellent information to stratify the risk of mortality in patients treated by percutaneous coronary intervention. The TIMI, CADILLAC, and GRACE models have higher predictive accuracy. The usefulness of these models for reinfarction and target-vessel revascularization prediction is questionable.

Renal insufficiency and vascular complications after primary angioplasty via femoral route. Impact of vascular closure devices use.

INTRODUCTION AND OBJECTIVES: We sought to determine the incidence of vascular complications in patients with chronic kidney disease undergoing primary angioplasty via the femoral route; we also evaluated the safety and efficacy of the use of vascular closure devices in this setting. METHODS: Registry of 527 patients undergoing primary angioplasty via the femoral route from January 2003 to December 2008. Chronic kidney disease was defined as creatinine clearance less than 60 mL/min. The primary endpoint was the presence of major vascular complications. RESULTS: Baseline chronic kidney disease was observed in 166 (31.5%) patients. Patients with chronic kidney disease experienced higher rates of major vascular complications compared to those without worsening of renal function (8.4% vs 4.2%; P=.045), especially those requiring transfusion (6.6% vs 1.9%; P=.006). Among patients with chronic kidney disease, 129 (77.7%) received a vascular closure device and manual compression was used in 37 patients (22.3%). The risk of major vascular complications was significantly lower with vascular closure device use compared to manual compression (4.7% vs 21.6%; P=.003). Multivariable logistic regression analysis showed that the use of a vascular closure device was independently associated with a decreased risk of major vascular complications in patients with chronic kidney disease undergoing primary angioplasty (odds ratio=0.11; 95% confidence interval, 0.03-0.41; P=.001). CONCLUSIONS: Patients with chronic kidney disease undergoing primary angioplasty via the femoral route experience higher rates of major vascular complications. The use of vascular closure devices in this group of patients is safe and is associated with lower rates of major vascular complications compared to manual compression.

Primary angioplasty in Northern Galicia: care changes and results following implementation of the PROGALIAM protocol.

INTRODUCTION AND OBJECTIVES: To analyze changes in healthcare delivery and results for primary angioplasty at Centro Hospitalario Universitario A Coruña following implementation of the PROGALIAM protocol. METHODS: Observational registry of 1434 patients referred for primary angioplasty between 2003 and 2007. Results under PROGALIAM (May 2005 - December 2007; n=963) were compared with those from the preceding period (January 2003 - April 2005; n=388). RESULTS: After implementing PROGALIAM, there were increases in the number of primary angioplasty procedures (preceding period, 14.4 cases/month; PROGALIAM, 32.2 cases/month), mean patient age (preceding period, 61.3 (11.9) years; PROGALIAM, 64.2 (11.7) years; P<.001), and the percentage of patients referred from peripheral hospitals and treated after normal working hours. Overall median first medical contact-to-balloon time increased (previous period, 106 min; PROGALIAM, 113 min; P=.02), but decreased significantly among patients referred from noninterventional centers (previous period, 171 min; PROGALIAM, 146 min; P<.001). Percentage of cases with an first medical contact-to-balloon time <120 min remained unchanged among interventional-center patients (preceding period, 69%; PROGALIAM, 71%; P=.56) and increased among patients at noninterventional centers, although it remained low in this subgroup (preceding period, 17%; PROGALIAM, 30%; P=.04). Thirty-day mortality (preceding period, 5.2%; PROGALIAM, 6.2%; P=.85) and 1-year mortality (preceding period, 9.5%; PROGALIAM, 10.2%; P=.96) remained unchanged. CONCLUSIONS: Implementation of PROGALIAM allowed us to increase the percentage of patients receiving primary angioplasty without jeopardizing the clinical results of this treatment.

Effect of stent thrombosis on the risk-benefit balance of drug-eluting stents and bare metal stents.

INTRODUCTION AND OBJECTIVES: To determine the difference in the risk of stent thrombosis between drug-eluting stents (DES) and bare-metal stents (BMS) and to assess the clinical implications. METHODS: A retrospective analysis of two cohorts of patients treated at our center with either > or =1 paclitaxeleluting stents (PES) (n=430) or > or =1 BMSs (n=1230) during 2003-2004 was carried out using propensity score methods to compare the adjusted risks of stent thrombosis, instent restenosis, cardiovascular death, acute myocardial infarction (AMI), and target-lesion revascularization with the two stent types. RESULTS: After a median follow-up of 46 months, there was a higher risk of stent thrombosis in PESs (hazard ratio [HR]=3; 95% confidence interval [CI], 1.2-7.1] though the risk of in-stent restenosis was lower (HR=0.3; 95% CI, 0.2-0.7]. There was no difference in the risk of cardiovascular death, AMI or target-lesion revascularization. With PESs, the risks of target-lesion revascularization (HR=0.33; 95% CI, 0.2-0.7) and in-stent restenosis (HR=0.32; 95% CI, 0.2-0.7) were reduced during the first year of follow-up. After this time, the risks of target-lesion revascularization (HR=1.8; 95% CI, 1-3.2) and very late stent thrombosis (HR=12.8; 95% CI, 3-55.1) both increased. CONCLUSIONS: Our findings indicate that the balance of risks and benefits of PESs compared with BMSs is different in the early and late periods after stent implantation. The greatly increased risk of very late stent thrombosis in PESs could cancel out the clinical benefits associated with the reduction in in-stent restenosis observed in PESs relative to BMSs.

Prevalence, etiology and outcome of catheterization laboratory false alarms in patients with suspected ST-elevation myocardial infarction.

INTRODUCTION AND OBJECTIVES: To investigate the prevalence, causes and outcome of catheterization laboratory false alarms (CLFAs) in a regional primary angioplasty network. METHODS: A prospective registry of 1,662 patients referred for primary angioplasty between January 2003 and August 2008 was reviewed to identify CLFAs (i.e. when no culprit coronary lesion could be found). RESULTS: No culprit coronary lesion could be identified in 120 patients (7.2%; 95% confidence interval [CI], 5.9-8.5%). Of these, 104 (6.3%, 95% CI, 5.1-7.4%) had a discharge diagnosis other than ST-elevation myocardial infarction, 91 (5.5%; 95% CI, 4.3-6.6%) had no significant coronary disease, and 64 (3.8%; 95% CI, 2.9-4.8%) tested negative for cardiac biomarkers. The most frequent alternative diagnoses were: previous Q-wave myocardial infarction (18 cases), nonspecific ST-segment abnormalities (11), pericarditis (10) and transient apical dyskinesia (10). The 30-day mortality rate was similar in patients with and without culprit lesions (5.8% vs. 5.8%; P=.99). The prevalence of CLFAs was slightly higher in patients not previously evaluated by a cardiologist and referred from emergency departments in hospitals without catheterization laboratories than in those referred by cardiologists from emergency departments at hospitals with such facilities (9.5% vs. 6.1%; P=.02; odds ratio=1.64; 95% CI, 1.08-2.5). The prevalence of CLFAs was not significantly higher in patients referred by physicians with out-of-hospital emergency medical services (7.2%; P=.51; odds ratio=1.37; 95% CI, 0.79-2.37). CONCLUSIONS: The prevalence of CLFAs was 7.2%, with the criterion of no culprit coronary lesion. Our findings suggest that different patterns of referral to catheterization laboratories could account for small variations in the prevalence of CLFAs.