Reperfusion therapy

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Reperfusion therapy is medical treatment that restores blood flow through blocked arteries, typically after a heart attack (myocardial infarction). Categories of reperfusion therapy thus include clot-busting (thrombolytic) drugs and procedures to open arteries with stents, or to graft arteries around blockages.[1] These interventions have become so central to the modern treatment of acute myocardial infarction, that we are said to be in the reperfusion era.[2][3] Patients who present with suspected acute myocardial infarction and ST segment elevation (STEMI) or new bundle branch block on the 12 lead ECG are presumed to have an occlusive thrombosis in an epicardial coronary artery. They are therefore candidates for immediate reperfusion, either with thrombolytic therapy, percutaneous coronary intervention (PCI) or when these therapies are unsuccessful, bypass surgery.

Individuals without a ST segment elevation are presumed to be experiencing either unstable angina (UA) or non-ST segment elevation myocardial infarction (NSTEMI). They receive many of the same initial therapies and are often stabilized with antiplatelet drugs and anticoagulants. If their condition remains (hemodynamically) stable, they can be offered either late coronary angiography with subsequent restoration of blood flow (revascularization), or non-invasive stress testing to determine if there is significant ischemia that would benefit from revascularization. If hemodynamic instability develops in individuals with NSTEMIs, they may undergo urgent coronary angiography and subsequent revascularization. The use of thrombolytic agents is contraindicated in this patient subset, however.[4]

The basis for this distinction in treatment regimens is that ST segment elevations on an ECG are typically due to complete occlusion of a coronary artery. On the other hand, in NSTEMIs there is typically a sudden narrowing of a coronary artery with preserved (but diminished) flow to the distal myocardium. Anticoagulation and antiplatelet agents are given to prevent the narrowed artery from occluding.

At least 10% of patients with STEMI don't develop myocardial necrosis (as evidenced by a rise in cardiac markers) and subsequent Q waves on EKG after reperfusion therapy. Such a successful restoration of flow to the infarct-related artery during an acute myocardial infarction is known as "aborting" the myocardial infarction. If treated within the hour, about 25% of STEMIs can be aborted.[5]

Thrombolytic therapy[edit]

Main article: Thrombolysis

Thrombolytic therapy is indicated for the treatment of STEMI if the drug can be administered within 12 hours of the onset of symptoms, the patient is eligible based on exclusion criteria, and primary PCI is not immediately available.[6] The effectiveness of thrombolytic therapy is highest in the first 2 hours. After 12 hours, the risk associated with thrombolytic therapy outweighs any benefit.[4][7] Because irreversible injury occurs within 2–4 hours of the infarction, there is a limited window of time available for reperfusion to work.

Thrombolytic drugs are contraindicated for the treatment of unstable angina and NSTEMI[4][8] and for the treatment of individuals with evidence of cardiogenic shock.[9]

Although no perfect thrombolytic agent exists, an ideal thrombolytic drug would lead to rapid reperfusion, have a high sustained patency rate, be specific for recent thrombi, be easily and rapidly administered, create a low risk for intra-cerebral and systemic bleeding, have no antigenicity, adverse hemodynamic effects, or clinically significant drug interactions, and be cost effective.[10] Currently available thrombolytic agents include streptokinase, urokinase, and alteplase (recombinant tissue plasminogen activator, rtPA). More recently, thrombolytic agents similar in structure to rtPA such as reteplase and tenecteplase have been used. These newer agents boast efficacy at least as well as rtPA with significantly easier administration. The thrombolytic agent used in a particular individual is based on institution preference and the age of the patient.

Depending on the thrombolytic agent being used, adjuvant anticoagulation with heparin or low molecular weight heparin may be of benefit.[11][12] With TPa and related agents (reteplase and tenecteplase), heparin is needed to maintain coronary artery patency (openness.) Because of the anticoagulant effect of fibrinogen depletion with streptokinase[13] and urokinase[14][15][16] treatment, it is less necessary there.[11]

Intracranial bleeding (ICB) and subsequent cerebrovascular accident (CVA) is a serious side effect of thrombolytic use. The risk of ICB is dependent on a number of factors, including a previous episode of intracranial bleed, age of the individual, and the thrombolytic regimen that is being used. In general, the risk of ICB due to thrombolytic use for the treatment of an acute myocardial infarction is between 0.5 and 1 percent.[11]

Thrombolytic therapy to abort a myocardial infarction is not always effective. The degree of effectiveness of a thrombolytic agent is dependent on the time since the myocardial infarction began, with the best results occurring if the thrombolytic agent is used within two hours of the onset of symptoms.[17][18] If the individual presents more than 12 hours after symptoms commenced, the risk of intracranial bleed are considered higher than the benefits of the thrombolytic agent.[19] Failure rates of thrombolytics can be as high as 20% or higher.[20] In cases of failure of the thrombolytic agent to open the infarct-related coronary artery, the patient is then either treated conservatively with anticoagulants and allowed to "complete the infarction" or percutaneous coronary intervention (PCI, see below) is then performed. Percutaneous coronary intervention in this setting is known as "rescue PCI" or "salvage PCI". Complications, particularly bleeding, are significantly higher with rescue PCI than with primary PCI due to the action of the thrombolytic agent.

Percutaneous coronary intervention[edit]

Thrombus material (in a cup, upper left corner) removed from a coronary artery during a percutaneous coronary intervention to abort a myocardial infarction. Five pieces of thrombus are shown (arrow heads).

The benefit of prompt, expertly performed primary percutaneous coronary intervention over thrombolytic therapy for acute ST elevation myocardial infarction is now well established.[21][22][23] When performed rapidly by an experienced team, primary PCI restores flow in the culprit artery in more than 95% of patients compared with the spontaneous recanalization rate of about 65%.[21] Logistic and economic obstacles seem to hinder a more widespread application of percutaneous coronary intervention (PCI) via cardiac catheterization,[24] although the feasibility of regionalized PCI for STEMI is currently being explored in the United States.[25] The use of percutaneous coronary intervention as a therapy to abort a myocardial infarction is known as primary PCI. The goal of primary PCI is to open the artery as soon as possible, and preferably within 90 minutes of the patient presenting to the emergency room. This time is referred to as the door-to-balloon time. Few hospitals can provide PCI within the 90 minute interval,[26] which prompted the American College of Cardiology (ACC) to launch a national Door to Balloon (D2B) Initiative in November 2006. Over 800 hospitals have joined the D2B Alliance as of March 16, 2007.[27]

One particularly successful implementation of a primary PCI protocol is in the Calgary Health Region under the auspices of the Libin Cardiovascular Institute of Alberta. Under this model, EMS teams responding to an emergency electronically transmit the ECG directly to a digital archiving system that allows emergency room physicians and/or cardiologists to immediately confirm the diagnosis. This in turn allows for redirection of the EMS teams to facilities prepped to conduct time-critical angioplasty, based on the ECG analysis. In an article published in the Canadian Medical Association Journal in June 2007, the Calgary implementation resulted in a median time to treatment of 62 minutes.[28]

The current guidelines in the United States restrict primary PCI to hospitals with available emergency bypass surgery as a backup,[6] but this is not the case in other parts of the world.[29]

Primary PCI involves performing a coronary angiogram to determine the anatomical location of the infarcting vessel, followed by balloon angioplasty (and frequently deployment of an intracoronary stent) of the thrombosed arterial segment. In some settings, an extraction catheter may be used to attempt to aspirate (remove) the thrombus prior to balloon angioplasty. While the use of intracoronary stents do not improve the short term outcomes in primary PCI, the use of stents is widespread because of the decreased rates of procedures to treat restenosis compared to balloon angioplasty.[30]

Adjuvant therapy during primary PCI includes intravenous heparin, aspirin, and clopidogrel. Glycoprotein IIb/IIIa inhibitors are often used in the setting of primary PCI to reduce the risk of ischemic complications during the procedure.[31][32] Due to the number of antiplatelet agents and anticoagulants used during primary PCI, the risk of bleeding associated with the procedure is higher than during an elective PCI.[33]

Coronary artery bypass surgery[edit]

Coronary artery bypass surgery during mobilization (freeing) of the right coronary artery from its surrounding tissue, adipose tissue (yellow). The tube visible at the bottom is the aortic cannula (returns blood from the HLM). The tube above it (obscured by the surgeon on the right) is the venous cannula (receives blood from the body). The patient's heart is stopped and the aorta is cross-clamped. The patient's head (not seen) is at the bottom.

Emergency bypass surgery for the treatment of an acute myocardial infarction (MI) is less common than PCI or medical management. From 1995 to 2004, the percentage of people with cardiogenic shock treated with primary PCI rose from 27.4% to 54.4%, while the increase in CABG treatment was only from 2.1% to 3.2%.[34] Emergency coronary artery bypass graft surgery (CABG) is usually undertaken to simultaneously treat a mechanical complication, such as a ruptured papillary muscle, or a ventricular septal defect, with ensueing cardiogenic shock.[35] In uncomplicated MI, the mortality rate can be high when the surgery is performed immediately following the infarction.[36] If this option is entertained, the patient should be stabilized prior to surgery, with supportive interventions such as the use of an intra-aortic balloon pump.[37] In patients developing cardiogenic shock after a myocardial infarction, both PCI and CABG are satisfactory treatment options, with similar survival rates.[38][39]

Coronary artery bypass surgery involves an artery or vein from the patient being implanted to bypass narrowings or occlusions on the coronary arteries. Several arteries and veins can be used, however internal mammary artery grafts have demonstrated significantly better long-term patency rates than great saphenous vein grafts.[40] In patients with two or more coronary arteries affected, bypass surgery is associated with higher long-term survival rates compared to percutaneous interventions.[41] In patients with single vessel disease, surgery is comparably safe and effective, and may be a treatment option in selected cases.[42] Bypass surgery has higher costs initially, but becomes cost-effective in the long term.[43] A surgical bypass graft is more invasive initially but bears less risk of recurrent procedures (but these may be again minimally invasive).[42]

Reperfusion dysrhythmia[edit]

Accelerated idioventricular rhythm (AIVR) which looks like slow ventricular tachycardia is a sign of a successful reperfusion.[44] No specific treatment of this rhythm is needed as it rarely changes into a more serious rhythm.[45]

References[edit]

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