Definitions and Clinical Trial Design Principles for Coronary Artery Chronic Total Occlusion Therapies: CTO-ARC Consensus Recommendations.

Over the past 2 decades, chronic total occlusion (CTO) percutaneous coronary intervention has developed into its own subspecialty of interventional cardiology. Dedicated terminology, techniques, devices, courses, and training programs have enabled progressive advancements. However, only a few randomized trials have been performed to evaluate the safety and efficacy of CTO percutaneous coronary intervention. Moreover, several published observational studies have shown conflicting data. Part of the paucity of clinical data stems from the fact that prior studies have been suboptimally designed and performed. The absence of standardized end points and the discrepancy in definitions also prevent consistency and uniform interpretability of reported results in CTO intervention. To standardize the field, we therefore assembled a broad consortium comprising academicians, practicing physicians, researchers, medical society representatives, and regulators (US Food and Drug Administration) to develop methods, end points, biomarkers, parameters, data, materials, processes, procedures, evaluations, tools, and techniques for CTO interventions. This article summarizes the effort and is organized into 3 sections: key elements and procedural definitions, end point definitions, and clinical trial design principles. The Chronic Total Occlusion Academic Research Consortium is a first step toward improved comparability and interpretability of study results, supplying an increasingly growing body of CTO percutaneous coronary intervention evidence.

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.

Guiding Principles for Chronic Total Occlusion Percutaneous Coronary Intervention.

Outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have improved because of advancements in equipment and techniques. With global collaboration and knowledge sharing, we have identified 7 common principles that are widely accepted as best practices for CTO-PCI. 1. Ischemic symptom improvement is the primary indication for CTO-PCI. 2. Dual coronary angiography and in-depth and structured review of the angiogram (and, if available, coronary computed tomography angiography) are key for planning and safely performing CTO-PCI. 3. Use of a microcatheter is essential for optimal guidewire manipulation and exchanges. 4. Antegrade wiring, antegrade dissection and reentry, and the retrograde approach are all complementary and necessary crossing strategies. Antegrade wiring is the most common initial technique, whereas retrograde and antegrade dissection and reentry are often required for more complex CTOs. 5. If the initially selected crossing strategy fails, efficient change to an alternative crossing technique increases the likelihood of eventual PCI success, shortens procedure time, and lowers radiation and contrast use. 6. Specific CTO-PCI expertise and volume and the availability of specialized equipment will increase the likelihood of crossing success and facilitate prevention and management of complications, such as perforation. 7. Meticulous attention to lesion preparation and stenting technique, often requiring intracoronary imaging, is required to ensure optimum stent expansion and minimize the risk of short- and long-term adverse events. These principles have been widely adopted by experienced CTO-PCI operators and centers currently achieving high success and acceptable complication rates. Outcomes are less optimal at less experienced centers, highlighting the need for broader adoption of the aforementioned 7 guiding principles along with the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, and training.

Repatriation to referral hospital after reperfusion of STEMI patients transferred for primary percutaneous coronary intervention: Insights of a Canadian regional STEMI care system.

BACKGROUND: In regional systems of ST-segment elevation myocardial infarction (STEMI) care, patients presenting to hospitals without percutaneous coronary intervention (PCI) are transferred to PCI-capable hospitals for primary PCI. Repatriation, a practice whereby such patients are transferred back to non-PCI referral hospitals after reperfusion is prevalent in many jurisdictions, yet little is known of this practice and its safety. METHODS: We studied 979 consecutive STEMI patients transported from the emergency department and catchment area of two non-PCI hospitals in Ontario, Canada to a regional PCI-hospital for primary PCI between January 2008 and June 2014. Logistic regression modeling was performed to determine factors associated with delayed repatriation beyond 24 hours and to evaluate the association between repatriation and index-admission mortality. RESULTS: Eight hundred and fifteen (83.2%) patients were repatriated with 524 (65.2%) patients repatriated within 24 hours. Factors independently associated with delayed repatriation included systolic blood pressure (OR 1.03 per 5 mmHg decrease, 95% CI 1.01-1.06, P= .04), requirement for mechanical ventilation (OR 24.9, 95% CI 5.4-115.3, P< .0001), ventricular arrhythmia (OR 3.0, 95% CI 1.3-6.6, P= .01), infarct-related artery (P= .03), final TIMI flow grade (P= .01) and access-site complications (OR 2.36, 95% CI 1.04-5.4, P= .04). After repatriation, 9 (1.3%) patients returned to the PCI-hospital for urgent care, and 16 (2.0%) died during index-admission. After adjustment, repatriation was not associated with increase in index-admission mortality (adjusted OR 0.46, 95% CI 0.16-1.32, P= .15). CONCLUSIONS: In a regional STEMI care system in Ontario, Canada, patients are routinely repatriated to non-PCI hospitals after primary PCI. This practice was associated with very low and acceptable rate of return to the PCI-hospital during index-admission without an adverse impact on short-term outcomes.

Chronic total occlusion percutaneous coronary intervention case selection and techniques for the antegrade-only operator.

Coronary chronic total occlusions (CTO) remain a difficult lesion subset to treat. Although CTOs are present at coronary angiography in 15-20% of patients, only a small fraction of eligible patients will be offered percutaneous treatment. Recent publications from centers with dedicated CTO programs using the full range of antegrade and retrograde techniques suggest success rates in the range of 90% even when little anatomic exclusion are used. However, many patients with clinically appropriate CTO targets have simpler anatomy that can predictably be managed without the selected skills and equipment. The purpose of this review is to provide skilled percutaneous coronary intervention operators who have not specialized in complex retrograde CTO techniques, an algorithm for the selection and antegrade management of appropriate CTO cases. Core equipment and techniques are discussed.

Balloon-Expandable and Self-Expanding Transcatheter Heart Valves: Friend or Foe?

Transcatheter aortic valve replacement (TAVR) with balloon-expandable (BE) or self-expanding (SE) transcatheter heart valves (THVs) is indicated for the treatment of high-risk patients with severe aortic stenosis. Limited data are available comparing the two THV designs, and evidence suggests that each may offer unique advantages. Herein are described two patients who underwent TAVR with BE-THV and SE-THV, and who each developed a device-related complication that was successfully treated by using the alternate THV design.

A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial.

AIMS: We sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined. METHODS AND RESULTS: Non-ST-elevation ACS patients (n = 640) with planned early cardiac catheterization via femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25, 50, 75, or 100% anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding through 30 days. Secondary endpoints included major bleeding and the composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischaemia. Enrolment in the 25% reversal arm was suspended after 41 patients. Enrolment was stopped after three patients experienced allergic-like reactions. Bleeding occurred in 65, 34, 35, 30, and 31% of REG1 patients with 25, 50, 75, and 100% reversal and heparin. Major bleeding occurred in 20, 11, 8, 7, and 10% of patients. Ischaemic events occurred in 3.0 and 5.7% of REG1 and heparin patients, respectively. CONCLUSION: At least 50% reversal is required to allow safe sheath removal after cardiac catheterization. REG1 appears a safe strategy to anticoagulate ACS patients managed invasively and warrants further investigation in adequately powered clinical trials of patients who require short-term high-intensity anticoagulation.

Long-term effects of percutaneous coronary intervention of the totally occluded infarct-related artery in the subacute phase after myocardial infarction.

BACKGROUND: Despite observations suggesting a benefit for late opening of totally occluded infarct-related arteries after myocardial infarction, the Occluded Artery Trial (OAT) demonstrated no reduction in the composite of death, reinfarction, and class IV heart failure over a 2.9-year mean follow-up. Follow-up was extended to determine whether late trends would favor either treatment group. METHODS AND RESULTS: OAT randomized 2201 stable patients with infarct-related artery total occlusion >24 hours (calendar days 3-28) after myocardial infarction. Patients with severe inducible ischemia, rest angina, class III-IV heart failure, and 3-vessel/left main disease were excluded. We conducted extended follow-up of enrolled patients for an additional 3 years for the primary end point and angina (6-year median survivor follow-up; longest, 9 years; 12 234 patient-years). Rates of the primary end point (hazard ratio, 1.06; 95% confidence interval, 0.88-1.28), fatal and nonfatal myocardial infarction (hazard ratio, 1.25; 95% confidence interval, 0.89-1.75), death, and class IV heart failure were similar for the percutaneous coronary intervention (PCI) and medical therapy alone groups. No interactions between baseline characteristics and treatment group on outcomes were observed. The vast majority of patients at each follow-up visit did not report angina. There was less angina in the PCI group through early in follow-up; by 3 years, the between group difference was consistently <4 patients per 100 treated and not significantly different, although there was a trend toward less angina in the PCI group at 3 and 5 years. The 7-year rate of PCI of the infarct-related artery during follow-up was 11.1% for the PCI group compared with 14.7% for the medical therapy alone group (hazard ratio, 0.79; 95% confidence interval, 0.61-1.01; P=0.06). CONCLUSIONS: Extended follow-up of the OAT cohort provides robust evidence for no reduction of long-term rates of clinical events after routine PCI in stable patients with a totally occluded infarct-related artery and without severe inducible ischemia in the subacute phase after myocardial infarction.

Long-term outcomes after a strategy of percutaneous coronary intervention of the infarct-related artery with drug-eluting stents or bare metal stents vs medical therapy alone in the Occluded Artery Trial (OAT).

BACKGROUND: The OAT, a randomized study of routine percutaneous coronary intervention or optimal medical therapy (MED) alone for the treatment of a totally occluded infarct-related artery in the subacute phase after myocardial infarction, showed similar rates of death, reinfarction and congestive heart failure (CHF) between study groups. Although most percutaneous coronary intervention patients were treated with bare metal stents (BMS), drug-eluting stents (DES) were also implanted in the latter part of the study. The aim of the study was to conduct an exploratory analysis of long-term outcomes for DES vs. BMS deployment vs. MED in the OAT. METHODS: Patients enrolled after February 2003 (when first DES was implanted) were followed (DES n = 79, BMS n = 393, MED n = 552) up to a maximum of 6 years (mean survivor follow-up 5.1 years). RESULTS: The 6-year occurrence of the composite end point of death, reinfarction and class IV CHF was similar [20.4% of DES, 18.9% of BMS and 18.4% of MED (P = .66)] as were the rates of the components of the primary end point. During the follow-up period, 33.4% of DES, 44.4% of BMS and 48.1% of MED patients, developed angina (P = .037). The rate of revascularization during follow up was 11.3%, 20.5% and 22.5% among these groups, respectively (P = .045). CONCLUSIONS: There is no suggestion of reduced long-term risk of death, reinfarction or class IV CHF with DES usage compared to BMS or medical treatment alone. An association between DES use and freedom from angina and revascularization relative to medical therapy is suggested.

Anticoagulation after subcutaneous enoxaparin is time sensitive in STEMI patients treated with tenecteplase.

The adequacy of anticoagulation with enoxaparin as an adjuvant to fibrinolytic therapy for STEMI is unclear and has implications for both efficacy and safety; especially in patients undergoing a pharmacoinvasive reperfusion strategy. A subset of fibrinolytic-treated patients in the WEST study was enrolled in a systematic anti-Xa substudy. All received ASA and subcutaneous (SQ) enoxaparin 1 mg/kg followed by TNK-tPA. Incremental IV dosing of enoxaparin (0.3-0.5 mg/kg) was allowed prior to percutaneous coronary intervention (PCI). Anti-Xa blood samples were drawn prior and after angiography. Data are presented as percentages, medians and IQRs. Forty-five patients underwent angiography 2.8 h (2.5-14.6) after fibrinolytic. The pre-angiography median anti-Xa acquired 179 min (153-875) after SQ enoxaparin was 0.48 U/ml (0.42-0.65); a relationship between anti-Xa activity and time from administration was evident (r = 0.418, p < 0.007). Without supplemental IV enoxaparin the 2nd anti-Xa acquired 218 min (195-930) after SQ enoxaparin was 0.48 U/ml (0.41-0.80, n = 29). After supplemental IV enoxaparin, the 2nd anti-Xa was 0.92 U/ml (0.72-1.10, n = 16). An incremental IV enoxaparin dose and anti-Xa relationship was demonstrated (r = 0.59, p = 0.001) i.e. no IV 0.48 U/ml (0.41-0.80, n = 29), 0.3 mg/kg IV 0.81 U/ml (0.63-1.00, n = 12), and 0.5 mg/kg IV 1.34 U/ml (1.16-1.54, n = 4). Most fibrinolytic treated STEMI patients receiving weight-adjusted SQ enoxaparin (1 mg/kg) had subtherapeutic anti-Xa levels (<0.5 U/ml) after ~3 h. A strategy of supplemental 0.3 mg/kg IV enoxaparin at time of PCI reliably achieved anti-Xa ≥ 0.5 U/ml. Our findings provide a rational novel strategy for anti-thrombotic management in STEMI patients undergoing a pharmacoinvasive reperfusion strategy.

Gender differences in symptoms of myocardial ischaemia.

AIMS: Better understanding of symptoms of myocardial ischaemia is needed to improve timeliness of treatment for acute coronary syndromes (ACS). Although researchers have suggested sex differences exist in ischaemic symptoms, methodological issues prevent conclusions. Using percutaneous coronary intervention (PCI) balloon inflation as a model of myocardial ischaemia, we explored sex differences in reported symptoms of ischaemia. METHODS AND RESULTS: Patients having non-emergent PCI, but not haemodynamic instability or left bundle branch block or non-acute coronary occlusion, were prospectively recruited. Pre-procedure, descriptions of pre-existing symptoms were obtained using open-ended questioning. Inflation was maintained for 2 min or until moderate discomfort or clinical instability occurred. During inflation, subjects were exhaustively questioned about their symptoms. Concurrent ECG data were collected. The final sample was 305 [39.7% women; mean age 63.9 (± 10.6)]. No sex differences were found in rates of chest or typical ischaemic discomfort, regardless of ischaemic status. Women were significantly more likely to report throat/jaw discomfort [odds ratio: 2.91; 95% confidence interval: 1.58-5.37] even after statistical adjustment for clinical and demographic variables. CONCLUSION: This prospective study with ECG-affirmed ischaemia found no statistically significant differences in women's and men's rates of chest and other typical symptoms during ischaemia, although women were more likely to experience throat and jaw discomfort. Currently both popular press and some patient education materials suggest women experience myocardial ischaemia differently from men. Steps to ensure women and health professionals are alert for the classic symptoms of myocardial ischaemia in women, as well as men, may be warranted.

Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR pharmacokinetic and pharmacodynamic substudy.

AIMS: Establishing factor IX inhibition in patients with acute coronary syndrome/non-ST-elevation myocardial infarction (ACS/NSTEMI), a setting characterized by increased factor IX activity, is critical to investigate the REG1 system in this target population. The REG1 system (Regado Biosciences, Basking Ridge, NJ) consists of pegnivacogin (RB006), an RNA aptamer that directly inhibits factor IXa, and anivamersen (RB007), its complementary control agent. METHODS AND RESULTS: RADAR is a Phase 2b study investigating the use of pegnivacogin in patients (n = 800) with ACS undergoing planned early cardiac catheterization. To validate dose selection and stability of anticoagulation throughout the time of cardiac catheterization at an early stage of the clinical trial, 33 patients, 22 of whom had not received recent prior heparin, underwent thorough pharmacokinetic and pharmacodynamic assessment. Fold prolongation of activated partial thromboplastin time (aPTT) was used to impute factor IX inhibition. Pegnivacogin 1 mg/kg rapidly achieved a high pegnivacogin plasma concentration (26.1 ± 4.6 µg/mL), prolonged the aPTT (mean aPTT 93.0 ± 9.5 s), and approached near complete factor IX inhibition (mean fold increase from baseline 2.9 ± 0.3). These levels remained stable from the time of drug administration through completion of the catheterization. CONCLUSION: Pegnivacogin administered at a weight-adjusted dose of 1 mg/kg consistently achieves a high level of factor IX activity inhibition among patients with ACS and provides stable anticoagulation during cardiac catheterization. These findings support the dose of pegnivacogin selected for the RADAR study.

Impact of collateral flow to the occluded infarct-related artery on clinical outcomes in patients with recent myocardial infarction: a report from the randomized occluded artery trial.

BACKGROUND: Collateral flow to the infarct artery territory after acute myocardial infarction may be associated with improved clinical outcomes and may also impact the benefit of subsequent recanalization of an occluded infarct-related artery. METHODS AND RESULTS: To understand the association between baseline collateral flow to the infarct territory on clinical outcomes and its interaction with percutaneous coronary intervention of an occluded infarct artery, long-term outcomes in 2173 patients with total occlusion of the infarct artery 3 to 28 days after myocardial infarction from the randomized Occluded Artery Trial were analyzed according to angiographic collaterals documented at study entry. There were important differences in baseline clinical and angiographic characteristics as a function of collateral grade, with generally lower-risk characteristics associated with higher collateral grade. Higher collateral grade was associated with lower rates of death (P=0.009), class III and IV heart failure (P<0.0001) or either (P=0.0002) but had no association with the risk of reinfarction. However, by multivariate analysis, collateral flow was neither an independent predictor of death nor of the primary end point of the trial (composite of death, reinfarction, or class IV heart failure). There was no interaction between angiographic collateral grade and the results of randomized treatment assignment (percutaneous coronary intervention or medical therapy alone) on clinical outcomes. CONCLUSIONS: In recent myocardial infarction, angiographic collaterals to the occluded infarct artery are correlates but not independent predictors of major clinical outcomes. Late recanalization of the infarct artery in addition to medical therapy shows no benefit compared with medical therapy alone, regardless of the presence or absence of collaterals. Therefore, revascularization decisions in patients with recent myocardial infarction should not be based on the presence or grade of angiographic collaterals. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004562.

A randomized, partially blinded, multicenter, active-controlled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system in patients with acute coronary syndromes: design and rationale of the RADAR Phase IIb trial.

Anticoagulants are the cornerstone of current acute coronary syndrome (ACS) therapy; however, anticoagulation regimens that aggressively reduce ischemic events are almost uniformly associated with more bleeding. REG1, an anticoagulation system, consists of RB006 (pegnivacogin), an RNA oligonucleotide factor IXa inhibitor, and RB007 (anivamersen), its complementary controlling agent. Phase I and IIa studies defined predictable relationships between doses of RB006, RB007, and degree of antifactor IX activity. The efficacy and safety of REG1 for the treatment of patients with ACS managed invasively and the safety of reversing RB006 with RB007 after cardiac catheterization are unknown. Randomized, partially-blinded, multicenter, active-controlled, dose-ranging study assessing the safety, efficacy, and pharmacodynamics of the REG1 anticoagulation system compared to unfractionated heparin or low molecular heparin in subjects with acute coronary syndrome (RADAR) is designed to assess both the efficacy of the anticoagulant RB006 and the safety of a range of levels of RB006 reversal with RB007. The objectives of RADAR are (1) to determine the safety of a range of levels of RB006 reversal with RB007 after catheterization, (2) to confirm whether a dose of 1 mg/kg RB006 results in near-complete inhibition of factor IXa in patients with ACS, and (3) to assess the efficacy of RB006 as an anticoagulant in patients with ACS undergoing percutaneous coronary intervention.

Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial.

AIMS: To examine the incidence of and propensity for non-culprit interventions performed at the time of the primary percutaneous coronary intervention (PCI) and its association with 90-day outcomes. METHODS AND RESULTS: We examined the incidence, propensity for, and associated 90-day outcomes following non-culprit interventions performed at the time of primary PCI among ST-elevation myocardial infarction patients with multi-vessel coronary artery disease (MVD). Of the 5373 patients who underwent primary PCI in the APEX-AMI trial, 2201 had MVD. Of those, 217 (9.9%) underwent non-infarct-related arteries (IRA) PCI, whereas 1984 (90.1%) underwent PCI of the IRA alone. Ninety-day death and death/CHF/shock were higher in the non-IRA group compared with the IRA-only PCI group (12.5 vs. 5.6%, P (log-rank) < 0.001 and 17.4 vs. 12.0%, P (log-rank) = 0.020, respectively). After adjusting for patient and procedural characteristics as well as propensity for performing non-IRA PCI, this procedure remained independently associated with an increased hazard of 90-day mortality [adjusted hazard ratio 2.44, 95% CI (1.55-3.83), P < 0.001]. CONCLUSION: Non-culprit coronary interventions were performed at the time of primary PCI in 10% of MVD patients and were significantly associated with increased mortality. Our data support current guideline recommendations discouraging the performance of such procedures in stable primary PCI patients. Prospective randomized study of this issue may be warranted.

The Canadian Contribution to Science, Techniques, Technology, and Education in Chronic Total Occlusion Percutaneous Coronary Intervention.

Chronic total occlusions are considered the most complex coronary lesions in interventional cardiology. This article reviews the Canadian clinical and academic contributions to this field, including innovative procedural techniques, teaching and proctoring, clinical research, and the development of novel tools and therapies.

L'occlusion totale chronique est considérée comme étant la lésion coronarienne la plus complexe dans le domaine de la cardiologie interventionnelle. Nous passons ici en revue les contributions des cliniciens et des universitaires canadiens dans ce domaine, notamment en matière de techniques d'intervention novatrices, d'enseignement et d'encadrement, de recherche clinique et de mise au point de nouveaux outils et traitements.

Global Chronic Total Occlusion Crossing Algorithm: JACC State-of-the-Art Review.

The authors developed a global chronic total occlusion crossing algorithm following 10 steps: 1) dual angiography; 2) careful angiographic review focusing on proximal cap morphology, occlusion segment, distal vessel quality, and collateral circulation; 3) approaching proximal cap ambiguity using intravascular ultrasound, retrograde, and move-the-cap techniques; 4) approaching poor distal vessel quality using the retrograde approach and bifurcation at the distal cap by use of a dual-lumen catheter and intravascular ultrasound; 5) feasibility of retrograde crossing through grafts and septal and epicardial collateral vessels; 6) antegrade wiring strategies; 7) retrograde approach; 8) changing strategy when failing to achieve progress; 9) considering performing an investment procedure if crossing attempts fail; and 10) stopping when reaching high radiation or contrast dose or in case of long procedural time, occurrence of a serious complication, operator and patient fatigue, or lack of expertise or equipment. This algorithm can improve outcomes and expand discussion, research, and collaboration.

Electrophysiological effects of late percutaneous coronary intervention for infarct-related coronary artery occlusion: the Occluded Artery Trial-Electrophysiological Mechanisms (OAT-EP).

BACKGROUND: The Occluded Artery Trial-Electrophysiological Mechanisms (OAT-EP) tested the hypothesis that opening a persistently occluded infarct-related artery by percutaneous coronary intervention and stenting (PCI) after the acute phase of myocardial infarction compared with optimal medical therapy alone reduces markers of vulnerability to ventricular arrhythmias. METHODS AND RESULTS: Between April 2003 and December 2005, 300 patients with an occluded native infarct-related artery 3 to 28 days (median, 12 days) after myocardial infarction were randomized to PCI or optimal medical therapy. Ten-minute digital Holter recordings were obtained before randomization, at 30 days, and at 1 year. The primary end point was the change in alpha1, a nonlinear heart rate variability parameter, between baseline and 1 year. Major secondary end points were the changes in the filtered QRS duration on the signal-averaged ECG and variability in T-wave morphology (T-wave variability) between baseline and 1 year. There were no significant differences in the changes in alpha1 (-0.04; 95% CI, -0.12 to 0.04), filtered QRS (2.2 ms; 95% CI, -1.4 to 5.9 ms), or T-wave variability (3.0 microV; 95% CI, -4.8 to 10.7 microV) between the PCI and medical therapy groups (medical therapy change minus PCI change). Multivariable analysis revealed that the results were unchanged after adjustment for baseline clinical variables and medication treatments during the Holter recordings. CONCLUSIONS: PCI with stenting of a persistently occluded infarct-related artery during the subacute phase after myocardial infarction compared with medical therapy alone had no significant effect on changes in heart rate variability, the time-domain signal-averaged ECG, or T-wave variability during the first year after myocardial infarction. These findings are consistent with the lack of clinical benefit, including no reduction in sudden death, with PCI for stable patients with persistently occluded infarct-related arteries after myocardial infarction in the main OAT.

Lack of benefit from percutaneous intervention of persistently occluded infarct arteries after the acute phase of myocardial infarction is time independent: insights from Occluded Artery Trial.

AIMS: The Occluded Artery Trial (OAT) (n = 2201) showed no benefit for routine percutaneous intervention (PCI) (n = 1101) over medical therapy (MED) (n = 1100) on the combined endpoint of death, myocardial infarction (MI), and class IV heart failure (congestive heart failure) in stable post-MI patients with late occluded infarct-related arteries (IRAs). We evaluated the potential for selective benefit with PCI over MED for patients enrolled early in OAT. METHODS AND RESULTS: We explored outcomes with PCI over MED in patients randomized to the

ST-segment recovery and outcome after primary percutaneous coronary intervention for ST-elevation myocardial infarction: insights from the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial.

BACKGROUND: Primary percutaneous coronary angioplasty is an effective and widely adopted treatment for acute myocardial infarction. A simple method of determining prognosis after primary percutaneous coronary intervention (PCI) would facilitate appropriate care and expedite hospital discharge. Thus, we determined the prognostic importance of various measures of ST-segment-elevation recovery after primary PCI in a large, contemporary cohort of patients with ST-elevation myocardial infarction. METHODS AND RESULTS: We analyzed ECG data describing the magnitude and extent of ST-segment elevation and deviation before and early after (ie, 30 minutes) primary PCI in the study cohort of 4866 subjects with electrocardiographically high-risk ST-elevation myocardial infarction enrolled in the Assessment of PEXelizumab in Acute Myocardial Infarction (APEX-AMI) trial. Associations among 6 methods for calculating ST-segment recovery, biomarker estimates of infarct size (ie, peak creatine kinase, creatine kinase-MB, and troponin I and T), and prespecified clinical outcomes (ie, rates of 90-day death and 90-day death, heart failure, or shock) were examined. All ST-segment-recovery methods provided strong prognostic information regarding clinical outcomes. A simple ST-segment-recovery method of residual ST-segment elevation measurement in the most affected lead on the post-PCI ECG performed as well as complex methods that required comparison of pre- and post-PCI ECGs or calculation of summed ST-segment deviation in multiple leads (ie, worst-lead residual ST elevation: adjusted hazard ratio for 90-day death rate [reference <1 mm]: 1 to <2 mm, 1.23 [95% CI 0.74 to 2.03]; > or =2 mm, 2.22 [95% CI 1.35 to 3.65], corrected c-index=0.832; 90-day death/congestive heart failure/shock [reference <1 mm]: 1 to <2 mm, 1.55 [95% CI 1.06 to 2.26]; > or =2 mm, 2.33 [95% CI 1.59 to 3.41], corrected c-index=0.802). Biomarker estimates of infarct size declined in association with enhanced ST-segment recovery. CONCLUSIONS: An ECG performed early after primary PCI is a simple, widely available, inexpensive, and powerful prognostic tool applicable to patients with ST-elevation myocardial infarction.