Late Open Artery Hypothesis Research Articles

Limitation of Infarct Size and the Open Artery Hypothesis: A Conversation With Eugene Braunwald, MD.

Eugene Braunwald received an MD from the New York University School of Medicine. He completed an internal medicine residency at Johns Hopkins Hospital and cardiology fellowships at Mount Sinai Hospital, Columbia University, and the National Heart Institute. He served as chief of cardiology and subsequently clinical director of the institute. From 1968 to 1972, he was the founding chair of medicine at the University of California, San Diego. From 1972 to 1996, he served as chair of medicine at the Brigham and Women’s Hospital. In 1975, he was elected to the National Academy of Sciences. He is now the Distinguished Hersey Professor of Medicine at Harvard Medical School and a senior investigator of the TIMI Study Group, which he founded in 1984. Dr Braunwald replies: I became aware of the importance of AMI in 1951 during an elective in cardiology during my senior year at the New York University School of Medicine. At the time, AMI was by far the most common cause of death in adults in the United States. Of the patients who survived to be admitted to hospitals (no one knew how many AMI patients failed to reach hospital emergency departments), about one third died before discharge, either suddenly, presumably from an arrhythmia, or secondary to pump failure. Of the patients who were discharged alive, about one quarter died within a year, most frequently as a consequence of heart failure or recurrent MI. Pathologists had taught that AMI was usually associated with coronary thrombosis. Indeed, during my cardiology elective, Herrick’s classic article describing AMI was required reading. Its title, “Clinical Features of Sudden Obstruction of the Coronary Arteries,” showed how these 2 conditions (coronary occlusion and AMI) were intertwined.1 My direct involvement in the care of several patients who did not survive the acute event left …

Benefits of coronary revascularization in stable patients in the short and long term after acute myocardial infarction

The benefit of coronary revascularization in stable patients with acute myocardial infarction presenting more than 12 h from onset of symptoms has been the subject of considerable debate. The late open artery hypothesis proposes that coronary revascularization may yield clinically relevant benefit even when performed more than 12 h from onset in a time-independent fashion through a variety of mechanisms. Patients who are most likely to benefit from late coronary revascularization include those presenting within 12–48 h, those with evidence of symptomatic or silent ischemia, those with myocardial viability and those with subtotal (rather than total) occlusion of the infarct-related artery. Asymptomatic patients with total occlusion of the infarct-related artery and no evidence of silent ischemia or viability are unlikely to benefit from percutaneous coronary intervention and should be managed with optimal medical therapy in the first instance.

The late open artery hypothesis: the case and the artery remain closed

The OAT trial1 was a key investigation, contributing to contemporary practice in the treatment of acute myocardial infarction (AMI). It unexpectedly demonstrated that for patients undergoing angiography between 3 and 28 days after AMI with poor or absent flow in a major infarct-related artery (IRA), re-establishing flow by percutaneous coronary intervention (PCI) provided no benefit, with indeed the suggestion of harm. There were some caveats to this statement, based on the specific population studied: the patients were a high-risk group, in that the lesion had to be in a proximal vessel, or there had to be an ejection fraction (EF) of <50%. The patients were also those about which little information was previously available regarding optimum treatment: the subtended myocardium had to be either dyskinetic or akinetic, or, if the myocardium was hypokinetic or normal, then mild or moderate (but not severe) ischaemia had to be present. This lack of benefit was despite … *Corresponding author. Tel: +612 9767 7358, Fax: +612 9767 6780, Email: ben{at}med.usyd.edu.au

Late medical versus interventional therapy for stable ST-segment elevation myocardial infarction

ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality, but timely reperfusion is known to result in dramatically improved patient outcomes. As many as 40% of patients with STEMI, however, present late after symptom onset, which reduces the likelihood of them receiving reperfusion therapy. The past two decades have been plagued with controversy regarding the relative benefits of reperfusion therapy after 12 h from symptom onset. Despite considerable data supporting late reperfusion and the 'late open-artery hypothesis', recent studies have demonstrated a lack of benefit with late reperfusion. Moreover, advances in the medical management of STEMI have dramatically reduced morbidity and mortality, further challenging the need for more-invasive techniques. Numerous questions have arisen regarding the appropriate management and risk stratification of asymptomatic post-STEMI patients who present late after symptom onset. In light of recent data, we present a Review of late reperfusion in STEMI, specifically highlighting the effects of current medical therapies, risk-stratification techniques, and indications for the use of late reperfusion over medical management.

Revascularization of the Infarct-Related Artery: Never Too Late?

During the early phase of an acute myocardial infarction (MI), current consensus is that reperfusion of the infarct-related artery (IRA) should be implemented as soon as possible, more effectively accomplished via percutaneous coronary intervention (PCI). The clinical approach to the occluded IRA late after MI remains controversial, but current practice shows a strong trend in favor of PCI, which is based on the late open artery hypothesis. However, late PCI on IRAs also has the potential for harm from procedure-related complications. An attempt is made herein to critically overview the current data on this important topic, mainly based on recent meta-analyses with somewhat diverging results, indicating that clinical judgment and an individualized approach still remains a valid guide.

The Late Open Infarct‐related Artery Hypothesis: Evidence‐based Medicine or Not?

Randomized clinical trials have clearly shown that early reperfusion of coronary arteries is the established treatment of myocardial infarction preserving left ventricular function and reducing mortality. However, late patency of the infarct-related artery is an independent predictor of survival leading to the late open-artery hypothesis. This concept implies restoration of antegrade blood flow of the infarct-related artery in patients with myocardial infarction to improve survival by mechanisms less time-dependent or even time-independent. Possible explanations for this benefit include improved left ventricular function and electrical stability by perfusion of hibernating myocardium, accelerated infarct healing and limitation of ventricular remodeling. This review focuses on the evidence of late recanalization of occluded infarct-related arteries in patients with coronary artery disease.

New frontiers and unresolved controversies in percutaneous coronary intervention

Percutaneous coronary intervention (PCI) has become a key modality of therapy of patients with coronary artery disease. However, with the exception of acute coronary syndromes, there is as yet no conclusive evidence from randomized controlled trials that PCI improves survival and outcome compared with optimal medical therapy. Randomized trials comparing PCI and coronary artery bypass grafting in patients with stable coronary artery disease conducted before stenting showed superiority of the surgical approach. Early results from stent trials continue to indicate better symptom relief and less need for repeat intervention with the surgical approach, although myocardial infarction and mortality are similar with the 2 revascularization modalities. In the setting of acute coronary syndromes, however, recent trials suggest superiority of an aggressive approach, including PCI, compared with a conservative strategy of medical therapy only. This benefit extends to patients with acute ST-elevation myocardial infarction, including those with shock. In the latter setting, mortality remains high and novel approaches to protect myocardial metabolism and improve perfusion will be needed to further improve survival. The role of revascularization in patients with completed myocardial infarction and persistently occluded arteries is much less clear. Although the late open artery hypothesis is widely accepted and interventional cardiologists routinely open late infarct-related coronary occlusions, the available evidence to justify this strategy is weak. New devices, such as thrombectomy devices in thrombus-laden lesions and drug-eluting stents, offer promise, although all lack the degree of proof of benefit and safety typically required of new pharmaceutical agents. As new technologies and therapies with the potential to improve outcomes and decelerate the atherosclerotic process are developed, it will be important for investigators and industry to collaborate in incorporating these advances into ongoing and new trials testing the efficacy of PCI in all settings.

Valoración de la viabilidad miocárdica en pacientes prerrevascularización

Information on myocardial viability can be useful to decide when coronary artery revascularization is indicated for patients with acute myocardial infarction (AMI) and left regional or global ventricular dysfunction. Difficulties in assessing viability arise because the same part of the ventricular wall can have a mixture of necrotic tissue and viable myocardium. Diagnostic markers of myocardial viability are: the preservation of wall thickness, the presence of contractility reserve, the presence of blood perfusion reserve, integrity of the wall cells, and preservation of cellular metabolism. Echocardiography and thallium or technetium imaging are methods currently used to assess myocardial viability because of their availability and relatively low cost. Although positron emission tomography (PET) has been considered the gold standard, its unavailability may limit its clinical use. Recent publications have demonstrated the accuracy of cardiac magnetic resonance imaging (cardiac MRI) in assessing myocardial viability, together with noninvasive procedures to study the markers of viability noted above. Late contrast enhancement with gadolinium is the most accurate and simplest method. The late open artery hypothesis recommends, on the basis of scant evidence, systematic revascularization of the culprit artery. Although no large randomized studies focused on prognosis are available yet, several small studies provide sufficient evidence of functional recovery of viable myocardium after coronary artery revascularization of the culprit artery in patients with global or regional ventricular dysfunction. The assessment of myocardial viability to decide whether culprit artery revascularization is indicated is a strategy currently based on more evidence than the more indiscriminate recommendations based on the late open artery hypothesis.

The late open artery hypothesis—A decade later

Background Early reperfusion after myocardial infarction has been proved to preserve left ventricular function and reduce mortality. However, a significant number of patients have persistent occlusion of the infarct-related artery late (days to weeks) after myocardial infarction because of ineligibility for thrombolytic therapy, failure of reperfusion, or reocclusion. Methods In this report we review the data on the potential mechanisms and benefits of late reperfusion and present prospective data on the incidence of and current practice patterns for the management of persistently occluded infarct-related arteries late after myocardial infarction. Results Although several studies have associated late patency of the infarct-related artery with improved long-term clinical outcome, they were nonrandomized and reflect selection bias. Furthermore, data on late patency from the largest study, Global Utilization of Steptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO-I), failed to confirm independent benefits of an open infarct-related artery 1 year after myocardial infarction. The randomized data on the effects of percutaneous transluminal coronary angioplasty for occluded infarct-related arteries late after myocardial infarction are limited and inconclusive. Conclusions The hypothesis that late reperfusion by percutaneous coronary intervention days to weeks after myocardial infarction results in improved long-term clinical outcomes in asymptomatic patients with occluded infarct-related artery is currently being tested in the randomized, multicenter Occluded Artery Trial. (Am Heart J 2001;142:411-21.)

Early reperfusion, late reperfusion, and the open artery hypothesis: An overview

Randomized clinical trials have clearly shown the beneficial effects of early reperfusion within 12 hours, and possibly up to 24 hours, after acute myocardial infarction (AMI). The data on late reperfusion beyond 24 hours are less convincing. Many studies show that an open infarct-related artery after MI, irrespective of the initial reperfusion strategy, is independently associated with improved long-term clinical outcome. However, similar analysis of the large Global Utilization of Streptokinase and tPA for Occluded Arteries (GUSTO) I study did not confirm this finding. It is unclear whether mechanical reperfusion of an occluded infarct-related artery late after MI (>24 hours) in asymptomatic patients will confer long-term benefits. The late open artery hypothesis, which proposes several mechanisms by which late reperfusion may offer benefit, remains to be tested in a large clinical trial. This overview focuses on the definitions of early reperfusion, late reperfusion, the relationship between timing of reperfusion and prognosis after AMI, and the late open artery hypothesis. Copyright © 2000 by W.B. Saunders Company Progress in Cardiovascular Diseases, Vol. 42, No. 6 (May/June), 2000: pp 397-404