Primary Angioplasty
Primary Angioplasty Edited by
David Antoniucci Head Division of Cardiology Careggi Hospital Viale Morgagni Florence 1-50134 Italy
MRCP(UK) MD
© 2004 Taylor & Francis, an imprint of the Taylor & Francis Group First published in the United Kingdom in 2004 by Taylor & Francis, an imprint of the Taylor & Francis Group, 11 New Fetter Lane, London EC4P 4EE This edition published in the Taylor & Francis e-Library, 2005. “To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.”
Tel.: Fax.: E-mail: Website:
+44 (0) 20 7583 9855 +44 (0) 20 7842 2298
[email protected] http://www.dunitz.co.uk
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of the publisher or in accordance with the provisions of the Copyright, Designs and Patents Act 1988 or under the terms of any licence permitting limited copying issued by the Copyright Licensing Agency, 90 Tottenham Court Road, London W1P 0LP. Although every effort has been made to ensure that all owners of copyright material have been acknowledged in this publication, we would be glad to acknowledge in subsequent reprints or editions any omissions brought to our attention. Although every effort has been made to ensure that drug doses and other information are presented accurately in this publication, the ultimate responsibility rests with the prescribing physician. Neither the publishers nor the authors can be held responsible for errors or for any consequences arising from the use of information contained herein. For detailed prescribing information or instructions on the use of any product or procedure discussed herein, please consult the prescribing information or instructional material issued by the manufacturer. A CIP record for this book is available from the British Library. ISBN 0-203-50747-9 Master e-book ISBN
ISBN 0-203-59598-X (Adobe eReader Format)
ISBN 1-84184-342-3 (Print Edition) Distributed in North and South America by Taylor & Francis 2000 NW Corporate Blvd Boca Raton, FL 33431, USA
Within Continental USA Te;.: 800 272 7737; Fax.: 800 374 3401 Outside Continental USA Tel.: 561 994 0555; Fax.: 561 361 6018 E-mail:
[email protected] Distributed in the rest of the world by Thomson Publishing Services Cheriton House North Way Andover, Hampshire SP10 5BE, UK Tel.: +44 (0)1264 332424 E-mail:
[email protected] Contents
Contributors
vii
Preface
ix
Section 1: The Clinical Perspective 1
Pathophysiological basics of acute myocardial infarction Guido Parodi
3
The epicardial vessel 䊏 The microcirculation 䊏 The myocardium
2
Major subgroups at presentation Angela Migliorini, Giampaolo Cerisano, Piergiovanni Buonamici, Guia Moschi
15
Electrocardiography 䊏 Echocardiography 䊏 Angiography 䊏 Elderly patients 䊏 Women 䊏 Diabetics 䊏 Cardiogenic shock
Section 2: The Technical Perspective 3
Techniques Angela Migliorini, Renato Valenti
45
Entry site 䊏 Guiding catheters 䊏 Coronary wires and angioplasty balloons 䊏 Techniques for assessment of the anatomy of a target vessel persistently occluded after crossing the wire 䊏 Thrombectomy 䊏 Emboli protection devices 䊏 Stents 䊏 Other techniques
4
Platelet glycoproteins IIb/IIIa inhibitors Renato Valenti, Guido Parodi, Angela Migliorini
59
Abciximab 䊏 Eptifibatide and tirofiban
5
Mechanical support Renato Valenti, Guido Parodi
65
Intraaortic balloon pumping 䊏 Other percutaneous mechanical circulatory support devices
Section 3: The Vessel Perspective 6
Right coronary artery (RCA) Renato Valenti, Angela Migliorini
7
Left anterior descending artery (LAD) Renato Valenti, Angela Migliorini
71 117
vi
Contents
8
Left circumflex artery (LCX) Renato Valenti, Angela Migliorini
149
9
Left main trunk (LMT) Renato Valenti, Angela Migliorini
163
Multivessel coronary intervention Renato Valenti, Angela Migliorini
169
10
Section 4: The Efficacy Perspective 11
Primary percutaneous coronary intervention for acute myocardial infarction in the ‘real world’ Renato Valenti, Emilio Vincenzo Dovellini, Giovanni Maria Santoro
179
Effectiveness of percutaneous mechanical intervention for AMI 䊏 Impact of time to treatment on outcome of patients treated by PCI for AMI 䊏 Institutional volume of primary PCI 䊏 Practice guidelines 䊏 Logistic models and organizational scenarios 䊏 Role of cardiac surgery backup
12
Assessment of myocardial reperfusion in acute myocardial infarction Giovanni Maria Santoro
187
The no-reflow phenomenon 䊏 Assessment of myocardial reperfusion
13
The concepts of rescue and facilitated percutaneous intervention in perspective Guido Parodi
201
Rescue angioplasty 䊏 Facilitated primary angioplasty 䊏 Transfer for primary angioplasty
Index
207
Contributors
David Antoniucci MD
Angela Migliorini MD
Head Division of Cardiology Careggi Hospital Viale Morgagni Florence I-50134 Italy
Associate Chief Division of Cardiology Careggi Hospital Viale Morgagni Florence I-50134 Italy
Piergiovanni Buonamici MD Associate Chief Division of Cardiology Careggi Hospital Viale Morgagni Florence I-50134 Italy
Guia Moschi MD Associate Chief Division of Cardiology Careggi Hospital Viale Morgagni Florence I-50134 Italy
Giampaolo Cerisano MD
Guido Parodi MD
Associate Chief Division of Cardiology Careggi Hospital Viale Morgagni Florence I-50134 Italy
Associate Chief Division of Cardiology Careggi Hospital Viale Morgagni Florence I-50134 Italy
Emilio Vincenzo Dovellini MD
Giovanni Maria Santoro MD
Associate Chief Division of Cardiology Careggi Hospital Viale Morgagni Florence I-50134 Italy
Head Division of Cardiology San Giovanni d’Dio Hospital Via di Torregalli 3 50143 Florence Italy
Renato Valenti MD Associate Chief Division of Cardiology Careggi Hospital Viale Morgagni Florence I-50134 Italy
Preface
Primary percutaneous coronary intervention (PCI) is the best therapeutic option for patients with acute myocardial infarction (AMI). The aim of this book is a complete and concise update on the rationale, techniques, and effectiveness of percutaneous mechanical revascularization for AMI. This aim has been achieved by the synergism of a complete and critical review of the key studies that are the foundation of evidence-based medicine with the so-called ‘technology of experience’. The latter is based on the experience of a high-volume center with more than 2000 patients with AMI treated by primary PCI, with no restriction based on clinical status on admission, and representative of the ‘real world’ of AMI. This growth in knowledge proceeded at the same pace as pioneering developments in new intervention techniques and adjunctive therapies, such as infarct artery stenting, direct stenting, thrombectomy, antiembolic protection devices, and the use of antiplatelet drugs. In this book, pathophysiologic and clinical aspects of AMI and reperfusion have been put in an interventional perspective, in order to provide the rationale for the best interventional approach to the patient with AMI.
A comprehensive review of interventional techniques is supported by a full description of cases representing different angiographic and clinical patient subsets. There are a number of previously controversial issues that we believe are no longer relevant and have not been discussed here. This is the case with the comparison between primary angioplasty and fibrinolysis, or the feasibility of primary angioplasty in current clinical practice. Again, general interventional cardiology issues that are not specific to AMI have not been addressed. These choices have resulted in an innovative format that includes four sections based on clinical, technical, procedural, and logistic aspects of mechanical intervention for AMI. The book may be read in a conventional way, from beginning to end, or alternatively, starting from one of the four sections, and then following all possible sequences for the remaining three sections. In addition to the Contributors, I would like to thank Vanda Boschi, one of the most extraordinary individuals involved in the primary PCI program of the Division of Cardiology of the Careggi Hospital, for her encouragement and unlimited support. David Antoniucci
Section 1 The Clinical Perspective
1 Pathophysiological basics of acute myocardial infarction Guido Parodi
The epicardial vessel Atherosclerotic plaque rupture in the coronary arteries is thought to underlie most acute coronary syndromes (ACS), including unstable angina and acute myocardial infarction (AMI), as well as many cases of sudden cardiac death, and thus is a major cause of overall mortality and morbidity.1 This process characterizes the clinical transition from stable coronary artery disease to acute coronary syndromes. Intracoronary thrombosis, the immediate result of plaque rupture, was hypothesized by Herrick2 to be the cause of AMI as early as 1912. However, plaque rupture and resulting intracoronary thrombosis were not universally accepted as major mechanisms underlying the ACS until the modern medical era. Large-scale randomized controlled trials confirming the efficacy of thrombolytic therapy were not performed until over 70 years after Herrick’s report.
Mortality from ACS began declining before thrombolysis became routine therapy,3 even due to treatments that ameliorate the effects of atherosclerotic plaque rupture (i.e. antithrombotics, antianginal therapy, and revascularization techniques). Novel approaches to the treatment of AMI remain necessary despite declining overall cardiac mortality. Thrombolytic therapy in the most recent large-scale randomized trials still yields high 1-month mortality and recurrent cardiac event rates.4
Atherosclerotic plaque morphology Types of atherosclerotic plaques vary widely in morphology, even when found in different locations in the coronary arteries of the same patients (Table 1.1).
Table 1.1 Atherosclerotic lesion types8 Plaque type
Characteristics of plaque
Clinical syndrome
I II, ‘Fatty streak’
Intimal thickening, macrophages, isolated foam cells Accumulation of intracellular lipid in infiltrating macrophages and smooth muscle cells Incipient extracellular lipid and connective tissue deposition Large extracellular intimal lipid core; inflammatory cell infiltration, including macrophages, foam cells, and T cells
Asymptomatic Asymptomatic
III IV, ‘Atheroma’
Va Vb Vc
Atheroma with fibrous layer or layers Atheroma with extensive calcification in the lipid core or elsewhere Fibrosed atheroma or organized mural thrombus with minimal or absent lipid components VI, ‘Complicated’ Disrupted type IV or V lesion with intramural hemorrhage and/or thrombosis
Asymptomatic Usually asymptomatic; can also be associated with stable angina Stable angina Stable angina Stable angina Acute coronary syndrome or asymptomatic lesion progression
4
Primary Angioplasty
Recent insights into the basic mechanisms involved in atherogenesis indicate that deleterious alterations of endothelial physiology, also referred to as endothelial dysfunction, represent a key early step in the development of atherosclerosis and are also involved in plaque progression and the occurrence of atherosclerotic complications.5 The initiation of atherosclerotic plaque has been correlated with the presence of a number of risk factors (e.g. hyperlipidemia, diabetes mellitus, hypertension, smoking, and aging) leading to endothelial dysfunction. This endothelial dysfunction is characterized by increased permeability, reduced synthesis and release of nitric oxide, and overexpression of adhesion molecules (e.g. intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and selectins), and chemoattractants (e.g. monocyte chemoattractant protein 1 (MCP-1), macrophage colony-stimulating factor (M-CSF), interleukin-1 (IL-1), IL-6, interferon-α (IFN-α), and IFN-γ). These processes facilitate the recruitment and internalization of circulating monocytes and low-density lipoprotein (LDL). The lipid material accumulated within the subendothelial space becomes oxidized and triggers an inflammatory response that induces the release of different chemotactic and proliferative growth factors. In response to these factors, smooth muscle cells and macrophages activate, migrate, and proliferate, resulting in thickening of the arterial wall.5,6 The earliest recognizable lesion of atherosclerosis is intimal thickening (type I lesion), an aggregation of lipid-rich macrophages and T lymphocytes within the innermost layer of the artery wall (the intima). Early lesions mature into others with smooth muscle cell infiltration and lipid (type II, ‘fatty streak’) and connective tissue deposition (type III).7 The ubiquity and precocity of the atherosclerotic process is attested by the finding of fatty streak in the coronary arteries of half of autopsy specimens from children aged 10–14 years. The early lesions develop within the first three decades of life in areas of localized turbulent flow within the coronary arteries.7 Their development is accelerated by conditions such as hypercholesterolemia, diabetes mellitus, hypertension, and smoking. As these early lesions grow into softer plaques with a high extracellular lipid and cholesteryl ester content and progressively thinner fibrous cap (types IV–Va, ‘atheroma’), they become more vulnerable to disruption.8 Ruptured plaques with overlying thrombus (type VI) are described as ‘complicated lesions’. These lesions contain a great number of cell types, including inflammatory cells and smooth muscle cells. When they achieve a degree of stenosis significant enough to decrease flow without sufficient collateral circulation, these lesions results in ACS. In the period after plaque rupture, thrombus over the complicated disrupted lesions organize, and the lesions calcify (type Vb) or fibrose (type Vc) into chronic stenotic lesions.8 However, advanced, stenotic plaques are not the only types that are prone to disruption. In fact, plaque disruption occurs independently of lesion size and degree of stenosis,
and the relationship is also complicated by vascular remodeling.3 Most AMI actually results from disruption of lesions that are not initially flow-limiting, with rapid progression to occlusion. Culprit lesions in AMI tend to have less calcification, which implies a certain softness of the plaque and vulnerability to shear forces and inflammatory components. Often, the complicated lesion has a central lipid core. However, the lipid composition and burden of complicated plaques can vary. Disrupted and thrombosed plaques with little lipid content have been described.3
Atherosclerotic plaque growth The coronary atherosclerotic lesion does not grow in a linear way. The gradual process by which material accumulates within the lesion is occasionally associated with sudden increases in plaque growth, which occur with plaque rupture and resulting intracoronary thrombosis. It is through these abrupt episodes of plaque rupture that even mildly or moderately stenotic plaques can acutely progress to totally occlusive lesions.3 Thus, abrupt episodes of plaque disruption, and growth, account for many cases of AMI. However, these episodes occur against a background of gradual atheromatous plaque growth that progresses over decades. The persistence of risk factors favors lesion growth – usually in an outward direction (positive remodeling) – for many years while preserving the lumen, and the silent inflammatory process continues.9 Several facts have been ascertained:10 • •
•
• •
plaque progression and clinical outcome are not necessarily closely related; many plaques progress episodically because of episodes of thrombosis triggered by rupture, erosion (denudation), or, occasionally, by endothelial activation or inflammation; some thrombi remain mural rather than occlusive, and produce few, if any, symptoms unless they embolize; and if lysis is incomplete and followed by re-endothelialization, the result is plaque growth; hemorrhage into the plaque can also result in rapid plaque growth; plaques in a given patient often progress unpredictably and largely independently from each other.
This frustrating unpredictability of patient outcome is probably due in part to fluctuations in risk factors and triggers (e.g. day-to-day changes in diet, blood pressure, smoking, activity, stress, pollution, and infection). Nevertheless, independent plaque behavior in a given patient must be due in large measure to the marked heterogeneity of plaque histology and to differences in the physical forces to which plaques are subjected.
Pathophysiological basics of acute myocardial infarction
The development and growth of the coronary atherosclerotic plaque can be subdivided into five phases based on lesion morphology and associated clinical sequelae:11 •
•
•
•
•
Phase 1: the asymptomatic development of lesions of types I–III occurs in most individuals in the first few decades of life. Phase 2: the atheroma (types IV and Va) develops; it is usually asymptomatic or may be accompanied by stable angina pectoris. Phase 3: plaque disruption occurs, resulting in a nonocclusive overlying mural thrombus and in the sudden growth of a complicated lesion (type VI); it is often asymptomatic, but may be accompanied by stable angina pectoris. Phase 4: plaque disruption (also a type VI lesion) is complicated by a large, often occlusive, thrombus; it is associated with AMI, unstable angina, or sudden cardiac death. Phase 5: phases 3 and 4 are followed by the development of chronic calcified (type Vb) or fibrotic (type Vc) lesions, which are often marked by stable angina pectoris. Severely stenotic lesions can occlude without plaque rupture from stasis in the vessel leading to thrombus. Occlusion of a phase 5 lesion is often clinically silent, as distal myocardium is frequently supplied by collateral flow.
Atherosclerotic plaque rupture A variety of mechanisms have been proposed as the initial cause of plaque rupture. The identification of mechanical and biological factors of plaque rupture has enhanced our understanding of the pathophysiology of AMI. Pathological studies have established the association between plaque rupture and thrombus formation. Two primary mechanisms can trigger the development of thrombus formation: frank rupture of the atheromatous fibrous cap, and superficial denudation of the endothelium. Rupture accounts for 60% or more of all thrombi associated with myocardial infarction or sudden cardiac death. Plaque erosion constitutes approximately 35% of the underlying mechanism of coronary thrombosis.11 Morphological and microscopic characteristics of the unstable plaque include (a) a thin fibrous cap (5 hours).30
Microvascular spasm Previous studies have shown that intracoronary administration of calcium- and sodium-channel blockers, such as verapamil and nicorandil, may attenuate microvascular dysfunction after reperfusion.31,32 These data support the hypothesis that vasoconstriction of distal microvasculature may play a role in the progression of capillary damage, likely mediated by abnormal calcium and sodium concentration and by vasoactive substances released from activated platelets (e.g. serotonin). The vasodilator reserve is impaired in postischemic vessels, secondary to endothelial dysfunction resulting in reduced generation of nitric oxide and prostacyclin,
Pathophysiological basics of acute myocardial infarction
enhanced endothelin formation, and damage to vascular adrenergic receptors. In addition, activated neutrophils release vasoconstriction mediators. The prevalence of vasoconstriction in postischemic vessels reduces the pressure gradient in the capillary bed, and favors further neutrophil cell accumulation.33 Coronary ischemia and stretch are known to increase, as a reflex, cardiac sympathetic nerve activity by the stimulation of cardiac ventricular and coronary receptors. After angioplasty, α-receptor-mediated vasoconstriction has been described. So, during mechanical reperfusion of AMI, intense α-adrenergic vasoconstriction can take place in the infarctrelated artery and then reduce myocardial perfusion.34 In patients with AMI, coronary regulatory function may be significantly impaired, even in areas of myocardium not directly supplied by the infarct-related artery. The impairment of microvascular function in remote areas may be explained by several possible mechanisms. Elevated left ventricular diastolic pressure may affect blood flow both in the infarct-related artery and in remote regions by decreasing coronary perfusion pressure. The generalized increase in neurohormonal sympathetic activity could lead to an impairment of vasodilator responsiveness in remote regions after infarction. Vasoconstrictive substances released at the site of coronary occlusion (e.g. serotonin, thrombin, and thromboxane A2) can constrict the vascular smooth muscle surrounding the thrombus, but they can also constrict distal vessels, leading to further blood flow stasis and coronary thrombosis. The vascular bed of non-infarct-related arteries can be influenced by systemic and local neurohormonal constrictor stimuli, resulting in an increase in the extent of ischemia and reducing collateral flow to the infarct-related artery.35
Collateral circulation Coronary collaterals offer an important alternative source of blood supply when the original vessel fails to provide sufficient blood, and timely recruitment of collaterals may avoid transmural myocardial infarction at the time of coronary occlusion.36 The functional coronary collateral circulation results from hypertrophic evolution of vessels with a lumen diameter of 20–350 µm that are present in normal hearts at birth. Recurrent and severe ischemia is assumed to stimulate the development of coronary collateral circulation. In fact, myocardial ischemia, per se, can be a sufficient stimulus to induce coronary collateral development, possibly through biochemical signals, including the release of angiogenic growth factor. The process is mediated mechanically through an increase in shear stresses. In the case of a hemodynamically relevant coronary stenosis, a pressure gradient is created and collateral arteries are recruited.
9
Because of the decrease in arterial pressure distal to the stenosis, blood flow is redistributed through the preexisting arterioles that now connect a high-pressure with a lowpressure area. These modifications result in an increased flow velocity and therefore increased shear stress in the preexisting collateral arteries, which leads to marked activation of the endothelium, upregulation of cell adhesion molecules, and increasing adherence of monocytes, which transform into macrophages. Subsequently, several morphological changes and vascular remodeling occur. Different growth factors and chemokines are involved in this process.36 At present, it is not clear why there are differences between individuals in their capability of developing a sufficient collateral circulation. Previous studies have shown that recurrent episodes of angina in the 24 hours before AMI are a stimulating factor for the development of collateral channels.37 Early recruitment of collateral circulation was more frequent in patients with acute right coronary artery occlusion, suggesting a more extensive collateralization from the left coronary system to the area supplied from the right coronary artery. Recruitment of collateral flow was also favored by a longer delay from symptom onset to treatment.36 Another condition associated with the development of coronary collaterals in AMI is the presence of total chronic occlusion. Conversely, cardiogenic shock, and baseline infarct artery TIMI grade >1 flow, are associated with a poor recruitment of collaterals.38 In patients treated by primary angioplasty for STsegment elevation AMI within 6 hours from symptom onset, the presence of collateral circulation is not an independent predictor of survival.38 It is likely that transmural myocardial ischemia subsequent to infarct artery occlusion is not significantly reduced by the early recruitment of collateral vessels, whereas the early restoration of the anterograde flow in the infarcted artery, provided by mechanical intervention, instantaneously overcomes the collateral flow in the area at risk. However, the development of coronary collaterals may help protect the myocardium from infarction during episodes of prolonged ischemia and may extend the limited numbers of ‘golden hours’ from the onset of coronary occlusion to successful tissue reperfusion.
The myocardium Ischemic injury The myocardium can tolerate brief minutes (up to 15 minutes) of severe or even total ischemia without resultant cardiomyocyte death. Although the cells suffer ischemic injury, the damage is reversible with prompt tissue reperfusion. With increasing duration and severity of ischemia, however, greater myocyte damage can develop,
10
Primary Angioplasty
with a predisposition to irreversible cell damage or necrosis. Complete necrosis of all myocardial cells at risk requires 4–6 hours or longer of ischemia, depending on the presence of collateral blood flow into the ischemic zone, the persistence or intermittency of artery occlusion, and the sensitivity of the myocytes.39 Sudden occlusion of a coronary artery is followed by physiological and metabolic changes that appear within seconds of the cessation of coronary flow. Energy metabolism shifts from aerobic or mitochondrial metabolism to anaerobic glycolysis after only 8 seconds.40 Simultaneously, effective contraction diminishes and then ceases, and the myocardium stretches rather than shortens with each systole. The membrane potential decreases and ECG changes appear. The demand of the myocytes for energy far exceeds the supply from anaerobic glycolysis, and from reserves of high-energy phosphate, resulting in decreased tissue ATP and accumulation of ADP. Anaerobic glycolysis provides 80% of the new high-energy phosphate produced in zones of total or severe ischemia, utilizing glucose from glycogenolysis as its substrate. The lactate and its associated H+ accumulate. After only 10 minutes of ischemia, intracellular pH decreases, and the load of intracellular osmotically active particles (lactate, inorganic phosphate, creatine, etc.) increases markedly, resulting in intracellular edema. In the absence of oxidative phosphorylation, ADP is converted to AMP, which in turn is broken down to adenosine and ultimately to inosine, hypoxanthine, and xanthine. A variety of substances, such as bradykinin, opioids, norepinephrine (noradrenaline), and angiotensin, are released into the extracellular fluid. These agents interact with adenosine, and stimulate intracellular signaling systems.40 A variety of potential causes of irreversible myocyte injury have been described: high-energy phosphate depletion and the cessation of anaerobic glycolysis; catabolism without resynthesis of macromolecules; reduced transsarcolemmal gradients of Na+ and K+ calcium overload; cell swelling; activation of phospholipases and proteases; impaired mithochondrial function; activation of ATPases; catabolite accumulation (lactate, inorganic phosphate, free radicals, H+ ammonia, and fatty acid derivatives); enzyme denaturation; membrane damage; and increased intracellular osmolarity.
be entirely beneficial, as there is also evidence that it may carry injurious components that may partly counteract the beneficial effects of the restoration of blood flow. This phenomenon has been called ‘reperfusion injury’.33 The principal mediators of reperfusion injury are reactive oxygen species (ROS) and neutrophils, which are redistributed by reperfusion in the previously ischemic tissue. ROS can attack every biologically relevant molecule. One important cardiac consequence might be peroxidation of unsatured lipids of cell membranes. This may be an important mechanism of cell damage, because the activity of membrane-bound enzymes can be affected by oxidation of membrane lipids. In addition to direct oxidative attack, ROS can also modulate various cellular activities that are important mediators in the sequence of events leading to tissue injury during reperfusion. The superoxide free-radical ion inactivates nitric oxide, whereas hydrogen peroxide can induce adherence of neutrophils to intact vessels via ICAM1 and CD18 interaction.33 Myocardial stunning is the best-established clinical manifestation of reperfusion injury. It is defined as ‘prolonged postischemic dysfunction of viable tissue salvaged by reperfusion’.40,41 This myocardium, after a prolonged but reversible dysfunction, requires a prolonged period of time before complete functional recovery. Microvascular dysfunction is another manifestation of reperfusion injury. Reperfusion causes marked endothelial cell dysfunction, which results in vasoconstriction, platelet and leukocyte activation, increased oxidant production, and increased fluid and protein extravasation. Finally, reperfusion of a severely ischemic myocardium may also result in myocyte death and necrosis (lethal reperfusion injury). A disruptive type of necrosis, termed contraction band necrosis, has been documented and is ascribed to massive myofibril contraction after reperfusioninduced calcium reentry. This form of reperfusion injury is the most severe, and is clearly irreversible.39 The past two decades have witnessed several pharmacological interventions designed to limit reperfusion injury. Unfortunately, no agent has shown convincing efficacy. The lack of a consistent clinical benefit may be related to a variety of factors, including poor clinical trial design, inadequate pharmacokinetic/pharmacodynamic studies, and the complexity of the phenomenon.39
Reperfusion injury Timely reperfusion has been clearly shown to be the most effective means to prevent progression of ischemic cell necrosis after coronary artery occlusion, and it is now widely accepted that prompt reopening of the occluded vessel, either by primary angioplasty or thrombolysis, must be pursued as soon as possible in patients with AMI. However, reperfusion of the previously ischemic myocardium may not
Myocardial stunning and hibernation There is convincing evidence that myocardium that has been reperfused after a relatively short period of ischemia is characterized by a variety of unfavorable, but not lethal, cellular changes that, given sufficient time, will revert to
Pathophysiological basics of acute myocardial infarction
normal. The most prominent of these changes is myocardial stunning, which is the prolonged contractile dysfunction that occurs despite the absence of irreversible injury and normal blood flow. Mechanical stunning is associated with a constellation of reversible derangements, including ATP depletion, collagen damage, cell swelling, increased capillary permeability, and impaired microvascular responsiveness. The duration of the dysfunction greatly exceeds that of the antecedent ischemia, for example, after 15 minutes of ischemia in dogs, myocardial function remains depressed for 24 hours.42 It seem certain that stunning also occurs in myocardium salvaged by arterial reperfusion after periods of 1–3 hours, i.e. periods that result in substantial amounts of necrosis in damaged tissue.42,43 A number of candidate underlying mechanisms for stunning have been investigated. Experimental studies have shown clearly that 50–70% of the stunning effect is due to a burst of O2-derived free-radicals (in particular, the hydroxyl radical) liberated during the first few minutes after reperfusion. This means that much of the stunning effect is a complication of reperfusion and therefore is a form of reperfusion injury.40 O2-derived free-radicals react quickly with proteins, phospholipids, and thiols. Nevertheless, a number of O2-derived free-radical scavengers have been tested without consistent benefits in human studies of myocardial infarction. Inotropic agents can override stunning. Administration of catecholamines, such as dobutamine, will restore contractile function to the control level, showing that the contractile systems of the myocyte (including those allowing Ca2+ entry and sarcoplasmic reticulum function, the myofibrils, and the mitochondria) are sufficiently preserved to allow full contraction. The exact changes that lead to the failure of contraction in myocardial stunning are unknown. Among the possibilities are any alterations in the availability of Ca2+ and the sensitivity of the contractile apparatus to calcium.40 During AMI a progressive wave front of cell death moves across the wall of the left ventricle from the subendocardial to the subepicardial layer. Myocardium salvaged by reperfusion is located primarily in the subepicardium and midmyocardium, and these layers displays the properties of stunned myocardium. Recovery of this tissue can be observed over the course of a variable period of time (from 3 days to 6 months), although most of the improvement is likely to take place within the first 7–10 days after infarction.40 Hibernation is a state of persistently impaired myocardial and left ventricular function at rest due to reduced coronary blood flow that can be partially or completely restored to normal if the myocardial oxygen supply/demand relationship is favorably altered, either by improving blood flow and/or by reducing demand.41,44 It has been proposed that the functional state of contractile failure of hibernation is due to chronic stunning caused by multiple episodes of more severe ischemia. Other experi-
11
mental studies, however, suggest that hibernation does occur with a chronic low-flow state.41 Whether the myocardial dysfunction is due to the downregulation of metabolism or to the chronic stunning, the treatment is clear: arterial flow must be improved.
Ischemic preconditioning Preconditioning is a powerful mechanism to protect the myocardium from ischemic damage. In the strictest sense, it refers to the delay in infarct development by one or more episodes of ischemia before persistent coronary occlusion. It is important to realize that the evolution to cell death is delayed but not prevented. Moreover, it appears that there is a bimodal distribution of protection, with an early phase (classic preconditioning) and a late phase.45 The mechanisms of ischemic preconditioning appear to be complex and involve second-messenger pathways. Myocardium that is preconditioned exhibits the striking metabolic changes noted during ischemic reversible injury, including a smaller adenine nucleotide pool (ATP + ADP + AMP), a creatine phosphate overshoot, an excess of intracellular glucose and lactate, and stunning. It has been postulated that preconditioned tissue dies slowly because of a reduction in energy demand.41 The results of some experimental studies provide strong evidence that adenosine is involved in preconditioning, with potassium channels being involved in mediating the effect of adenosine. Strong data exist that the beneficial effect of adenosine on preconditioning may be mediated via the A1 receptor.41 Several clinical studies have suggested that brief episodes of ischemia (angina) occurring before an AMI may have protective effects by ischemic preconditioning. Preinfarction angina can reduce myocardial infarct size and arrhythmias, resulting in improved left ventricular function, prevention of left ventricular remodeling, and increased survival.41,46 However, not all preinfarction angina studies have shown its protective effect,47 and there is still debate as to whether preinfarction angina has any benefit in elderly patients.
Ventricular remodeling Acute loss of myocardium results in an abrupt increase in loading conditions that induces a remodeling process involving the infarcted border zone and remote noninfarcted myocardium. Myocyte necrosis and the resulting increase in load trigger a cascade of biochemical intracellular signaling processes that initiates and subsequently modulates reparative changes, which include dilation, hypertrophy, and collagen synthesis. This balance is determined by the size, transmurality, and location of the infarct,
12
Primary Angioplasty
patency of the infarct-related artery, microvascular integrity in the area at risk, residual myocardial viability, left ventricular diastolic function, ischemic preconditioning, and neurohormonal activation.48,49,50 Remodeling encompasses cellular changes, including myocyte hypertrophy, necrosis, apoptosis, and fibrosis, and increased fibrillar collagen and fibroblast proliferation. As the heart remodels, its geometry changes: it becomes less elliptical and more spherical, and ventricular masses and volumes increase – all of which may adversely affect cardiac function.48 Postinfarction remodeling has been arbitrarily categorized into an early phase (within 72 hours) and a late phase (beyond 72 hours). The early phase involves expansion of the infarct zone, which may result in early ventricular rupture or aneurysm formation. Late remodeling involves the left ventricle globally, and is associated with chamber dilation, distortion of ventricular shape, and mural hypertrophy. Failure to normalize increased wall stresses results in progressive ventricular dilation, recruitment of border zone myocardium into the scar, and deterioration of contractile function.47 Left ventricular remodeling after AMI is an important predictor of hospitalization for heart failure and mortality. The remodeling process is heterogeneous, but the specific pattern of left ventricular dilation (early, late, and progressive) does not independently affect clinical outcome.50
2.
Herrick JB. Clinical features of sudden obstruction of the coronary arteries. JAMA 1912; 59: 2015–20.
3.
Gutstein DE, Fuster V. Pathophysiology and clinical significance of atherosclerotic plaque rupture. Cardiovasc Res 1999; 41: 323–33.
4.
Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of randomized trials. Lancet 2003; 361: 13–20.
5.
Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction. A marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 2003; 23: 168–75.
6.
Corti R, Fuster V. New understanding, diagnosis, and prognosis of atherothrombosis and the role of imaging. Am J Cardiol 2003; 91(Suppl 3A): 17A–26A.
7.
Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801–9.
8.
Stary HC, Chandler AB, Dinsmore RE, et al A definition of advanced types of atherosclerotic lesions and a histologic classification of atherosclerosis: a report from the Committee on Atherosclerosis. American Heart Association. Circulation 1995; 92: 1355–74.
9.
Libby P. Vascular biology of atherosclerosis: overview and state of the art. Am J Cardiol 2003; 91(Suppl 3A): 3A–6A.
10.
Casscells W, Naghavi M, Willerson JT. Vulnerable atherosclerotic plaque. A multifocal disease. Circulation 2003; 107: 2072–5.
11.
Fuster V, Lewis A. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation 1994; 90: 2126–46.
12.
Arroyo LH, Lee RT. Mechanisms of plaque rupture: mechanical and biologic interactions. Cardiovasc Res 1999; 41: 369–75.
13.
Cheng GC, Loree HM, Kamm RD et al. Distribution of circumferential stress in ruptured and stable atherosclerotic lesions: a structural analysis with histopathologic correlation. Circulation 1993; 87: 1179–87.
14.
Richardson PD, Davies MJ, Born GVR. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989; 2: 941–4.
15.
Ross R. Atherosclerosis. An inflammatory disease. N Engl J Med 1999; 340: 115–26.
16.
Rentrop KP. Thrombi in acute coronary syndromes. Revisited and revised. Circulation 2000; 101: 1619–26.
17.
van der Wal AC, Becker AE. Atherosclerotic plaque
Infarct expansion Infarct expansion results from degradation of intermyocyte collagen struts by serine proteases and the activation of MMPs released from neutrophils. Infarct expansion occurs early from myocyte injury, and results in wall thinning, ventricular dilation, and elevation of diastolic and systolic wall stresses. Infarct expansion causes deformation of the border zone and remote myocardium, which alters the Frank–Starling relations and augments shortening. Perturbations of circulatory hemodynamics trigger the sympathetic adrenergic system, which stimulates catecholamine synthesis, activates the renin–angiotensin–aldosterone system, and stimulates the production of atrial and brain natriuretic peptides. Augmented shortening and increased heart rate from sympathetic stimulation result in hyperkinesis of the noninfarcted myocardium and temporary circulatory compensation. In addition, the natriuretic peptides reduce intravascular volume and systemic vascular resistance, normalize ventricular filling, and improve pump function.48,51
References 1.
Maseri A, Fuster V. Is there a vulnerable plaque? Circulation 2003; 107: 2068–71.
Pathophysiological basics of acute myocardial infarction
rupture. Pathologic basis of plaque stability and instability. Cardiovasc Res 1999; 41: 334–44. 18.
19.
Hanratty CG, Koyama Y, Rasmussen HH et al. Exaggeration of nonculprit stenosis severity during acute myocardial infarction: implications for immediate multivessel revascularization. J Am Coll Cardiol 2002; 40: 911–6.
13
31.
Taniyama Y, Ito H, Iwakura K, et al. Beneficial effect of verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. J Am Coll Cardiol 1997; 30: 1193–9.
32.
Ito H, Taniyama Y, Iwakura K, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior myocardial infarction. J Am Coll Cardiol 1999; 33: 654–60.
33.
Ambrosio G, Tritto I. Reperfusion injury: Experimental evidence and clinical implications. Am Heart J 1999; 138(Suppl 2): S69–S75.
Ambrose JA, Martinez EE. A new paradigm for plaque stabilization. Circulation 2002; 105: 2000–4.
20.
Rezkalla SH, Kloner RA. No-reflow phenomenon. Circulation 2002; 105: 656–62.
21.
Reiner JS, Lundergan CF, Fung A, et al. Evolution of early TIMI 2 flow after thrombolysis for acute myocardial infarction. GUSTO-1 Angiographic Investigators. Circulation 1996; 94: 2441–6.
34.
Gregorini L, Marco J, Kozàcova M, et al. α-Adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction. Circulation 1999; 99: 482–90.
22.
Topol EJ, Yadav JS. Recognition of the importance of embolization in atherosclerotic vascular disease. Circulation 2001; 101: 570–80.
35.
Uren NG, Crake T, Lefroy DC, et al. Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction. N Engl J Med 1994; 331: 222–7.
23.
Ito H, Maruyama A, Iwakura K, et al. Clinical implications of the ‘no-reflow’ phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation 1996; 93: 223–8.
36.
Koerselman J, van der Graaf Y, de Jaegere PPT, Grobbee DE. Coronary collaterals. An important and underexposed aspect of coronary artery disease. Circulation 2003; 107: 2507–11.
24.
Wu KC, Zerhouni EA, Judd RM, et al. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 1998; 97: 765–72.
37.
Rentrop KP, Cohen M, Blancke H, et al. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985; 5: 587–92.
25.
Rochitte CE, Lima JC, Bluemke DA, et al. Magnitude and time course of microvascular obstruction and tissue injury after acute myocardial infarction. Circulation 1998; 98: 1006–14.
38.
Antoniucci D, Valenti R, Moschi G, et al. Relation between preintervention angiographic evidence of coronary collateral circulation and clinical and angiographic outcomes after primary angioplasty or stenting for acute myocardial infarction. Am J Cardiol 2002; 89: 121–5.
26.
Agati L. Microvascular integrity after reperfusion therapy. Am Heart J 1999; 138(Suppl 2): S76–8.
39.
27.
Tanaka A, Kawarabayashi T, Nishibori Y, et al. No-reflow phenomenon and lesion morphology in patients with acute myocardial infarction. Circulation 2002; 105: 2148–52.
Verma S, Fedak PWM, Weisel RD et al. Fundamentals of reperfusion injury for the clinical cardiologist. Circulation 2002; 105: 2332–6.
40.
Kloner RA, Jennings RB. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications. Part I. Circulation 2001; 104: 2981–9.
41.
Kloner RA, Jennings RB. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications. Part II. Circulation 2001; 104: 3158–67.
42.
Braunwald E, Kloner RA. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation 1982; 66: 1146–9.
43.
Ferrari R, Pepi P, Ferrari F, et al. Metabolic derangement in ischemic heart disease and its therapeutic control. Am J Cardiol 1998; 82(Suppl 5A): K2–13.
44.
Rahimtoola SH. The hibernating myocardium. Am Heart J 1989; 117: 211–21.
28.
29.
30.
Byrne JG, Appleyard RF, Lee CC, et al. Controlled reperfusion of the regionally ischemic myocardium with leukocytes-depleted blood reduces stunning, the no-reflow phenomenon, and infarct size. J Thorac Cardiovasc Surg 1992; 103: 66–72. Marzilli M, Orsini E, Marraccini P, Testa P. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation 2000; 101: 2154–9. Christiansen JP, Leong-Poi H, Klibarov AL et al. Noninvasive imaging of myocardial reperfusion injury using leukocyte-targeted contrast echocardiography. Circulation 2002; 105: 1764–7.
14
Primary Angioplasty
45.
Ferrari R, Ceconi C, Curello S, et al. Ischemic preconditioning, myocardial stunning, and hibernation: basic aspects. Am Heart J 1999; 138(Suppl 2): S61–8.
46.
Neskovic AN, Bolognese L, Parodi G, et al. Protective effect of preinfarction angina on left ventricular remodeling after primary coronary angioplasty. Circulation 2002; 106(Suppl II); II-527 (abst).
47.
Zahn R, Schiele R, Schneider S, et al. Effect of preinfarction angina pectoris on outcome of patients with acute myocardial infarction treated with primary angioplasty (Results from the Myocardial Infarction Registry). Am J Cardiol 2001; 87: 1–6.
48.
St John Sutton MG, Sharpe N. Left ventricular remodeling
after myocardial infarction. Pathophysiology and therapy. Circulation 2000; 101: 2981–8. 49.
Cohn JN, Ferrari R, Sharpe N. Cardiac remodelling. Concepts and clinical implications: a consensus paper from an International forum on cardiac remodeling. J Am Coll Cardiol 2000; 35: 569–82.
50.
Bolognese L, Neskovic N, Parodi G, et al. Left ventricular remodeling after primary coronary angioplasty: patterns of left ventricular dilation and long-term prognostic implications. Circulation 2002; 106: 2351–7.
51.
Mukherjee R, Brinsa TA, Dowdy KB, et al. Myocardial infarct expansion and matrix metalloproteinase inibition. Circulation 2003; 107: 618–25.
2 Major subgroups at presentation Angela Migliorini, Giampaolo Cerisano, Piergiovanni Buonamici, Guia Moschi
Electrocardiography The electrocardiogram (ECG) remains a crucial tool in the timely identification of acute myocardial infarction (AMI) and in the early selection of patients who will benefit from reperfusion therapies. A detailed analysis of patterns of STsegment elevation may influence decisions regarding the use of percutaneous coronary interventions (PCI), which are, according to the Recommendation Task Force of the European Society of Cardiology, ‘the preferred therapeutic option when it can be performed within 90 minutes after the first medical contact’.1 The specificity of the ECG in AMI is limited by large individual variations in coronary anatomy as well as by the presence of preexisting coronary artery disease, particularly in patients with a previous myocardial infarction, chronic occlusion, collateral circulation, or previous coronary bypass surgery. The ECG is also limited by its inadequate presentation of the posterior, lateral, and apical walls of the left ventricle (LV).2 The optimum ECG variables for the detection of AMI are ST-segment elevation of 1 mm or more in at least one lead, either inferior (II, III, aVF) or lateral (V5, V6, I, aVL), and ST-segment elevation of 2 mm or more in at least one anterior lead (V1–V4). Such a model has a 56% sensitivity and 94% specificity. Changing the degree of ST segment elevation greatly modifies both sensitivity and specificity.3
Left anterior descending coronary artery occlusion The earliest signs of AMI are subtle, and include increased T-wave amplitude over the affected area. T waves become
more prominent, symmetrical, and pointed (‘hyperacute’). These changes in T waves are usually present for only 5–30 minutes after the onset of the infarction, and are followed by ST segment changes. In practice, ST-segment elevation is often the earliest recognized sign of AMI.4 After occlusion of the left anterior descending coronary artery (LAD), ST-segment elevation of 1 mm or more is most frequently observed in V2 (sensitivity 91–99%) and then, in decreasing order of frequency, in V3, V4, V5, aVL, V1, and V6. The maximum ST elevation is recorded in V2 or V3.3 Powerful predictors of proximal LAD occlusion include ST-segment elevation in leads I and aVL, and ST-segment depression in inferior leads. ST-segment elevation in leads I and aVL often coexists with inferior ST-segment depression.3 The electrical activity of the anterolateral wall of the LV (supplied by both the first diagonal and the first obtuse marginal branches) is captured well by leads aVL and I. During an acute anterior infarction, a culprit lesion at the level of the first diagonal can be suspected when precordial ST-segment elevation is associated with ST-segment elevation in aVL (highly specific) and when ST-segment elevation is present in both leads I and aVL (highly sensitive combination also for diagonal occlusion). Occlusion of the first diagonal may produce unique ECG changes characterized by ST-segment elevation in the noncontiguous leads aVL and V2, plus ST-segment depression in leads III and aVF or in V4. When ST-segment elevation in leads I and aVL is accompanied by ST-segment depression in lead V2, the culprit lesion is usually the first marginal branch of the left circumflex artery (LCX).3 Moreover, four ECG signs have recently been found to be specific for occlusions at the level of the first septal perforator; these include ST-segment elevation in aVR, disappearance of preexisting septal Q waves in lateral
16
Primary Angioplasty
leads, ST-segment depression in V5, and right bundle branch block.3,5 Finally, distal LAD occlusions usually have ST-segment elevation of 3.2 mm or less in V2 and slight to moderate ST-segment elevation in V3. Other common findings are new Q waves in V4–V6 and augmented R-wave amplitude in V2. This pattern of acute right septal conduction delay results from ischemic disruption of the right septal activation vectors, and may be indistinguishable from the changes observed in recent or old posterior infarction.3 The significance of ST-segment elevation in lead V1 deserves a specific comment. Lead V1 captures electrical phenomena from the right septal area, which is supplied by the septal branches of the LAD. In some patients, the septum is additionally protected by a blood supply from a conal branch of the right coronary artery (RCA). This explains why approximately two-thirds of patients with anterior AMI have no ST-segment elevation in V1. The presence of ST-segment elevation in V1 correlates strongly with ST-segment elevation in V3R and predicts the less common anatomic scenario in which a small conal branch of the RCA does not reach the interventricular septum. RCA occlusion is found in 7% of patients with ST-segment elevation in leads V1–V4 who undergo coronary angiography.3
V3/III intermediate ratios. The absence of ST-segment depression in leads V1 and V2 rules out LCX occlusion, with a predictive value of over 90%.6 ST-segment elevation in leads I–aVL or V5–V6 is frequently accompanied by STsegment depression in lead aVR. This sign is independent of ST-segment depression in V1, and indicates a larger infarct size. However, lead aVR is frequently ignored in clinical practice, despite the demonstration of high predictive value of ST-segment changes from this lead.3 The vascular beds of the LCX have broad anatomic variability and may supply a rather small ventricle area. This is why the standard 12-lead ECG shows ST-segment elevation in less than half of cases of LCX occlusion. When present, ST-segment elevation is more often seen in leads II, III, and aVF, followed by leads V5, V6, and aVL. Onethird of patients with chest pain secondary to LCX occlusion have isolated ST-segment depression in the ECG; ST-segment depression in leads V1–V2 is a sensitive sign. Another third of patients will not have any changes in the 12-lead ECG.3
Special ECG injury patterns Anterior plus inferior injury
Right coronary artery or circumflex occlusion The typical ECG pattern of inferior infarction consists of STsegment elevation in leads II, III, and aVF. The occlusion is in the RCA in 80–90% of the cases, and in the LCX in the remaining patients. Higher ST-segment elevation in lead III than in lead II strongly suggests RCA disease. Because the only lead that faces the superior part of the LV and directly opposes the inferior wall is aVL, ST-segment depression in lead aVL is almost always determined by RCA occlusion. Injury in leads II, III, aVF without ST-segment depression in aVL indicates proximal LCX occlusion.2 The arteries that supply the posterolateral region of the LV are the obtuse marginal branch of the LCX, the posterolateral, and the LAD branches. Thus, ST-segment changes in leads V5–V6 indicate posterolateral ischemia triggered by either RCA or LCX occlusion. When STsegment elevation is significant (>2 mm), it is probably a sign of a large ischemic burden related to a very large artery.3 Precordial ST-segment depression accompanying inferior injury is more likely to develop from LCX than from RCA occlusion. The degree of ST-segment depression in V3 compared with the degree of ST-segment elevation in lead III (the ‘V3/III ratio’) is highest (1.2) when the occlusion is in the LCX and lowest (5 mm) is also suggestive of myocardial infarction in the presence of LBBB.9 The left bundle branch usually receives blood from the LAD and from the RCA. When a new LBBB occurs in the
17
•
Has myocardium been optimally reperfused, and how much myocardium has the potential to further recover during follow-up? Is monitoring of LV function/geometry able to identify early predictors of unfavorable remodeling?
Beyond its traditional diagnostic role (Table 2.1), echocardiography has become an important and powerful
Table 2.1 Echocardiography in patients with acute myocardial infarction (AMI): key points Traditional role of echocardiogram • Diagnosis of AMI in patients with a nondiagnostic electrocardiogram • Risk stratification through the assessment of left ventricular (LV) function • Diagnosis of mechanical complications of AMI Emergent role of echocardiogram • Evaluation of effectiveness of reperfusion therapy • Evaluation of functional recovery of postischemic myocardium (myocardial viability) • Early risk stratification for LV remodeling Future role of echocardiogram • Evaluation of intravenous myocardial contrast echocardiographic (MCE) imaging for determining optimal AMI treatment strategies • Echo-guided device application in the beating heart for repair of ischemic mitral regurgitation
18
Primary Angioplasty
tool because it has the potential to adequately address all these two main issues, and to participate in the therapeutic process. This chapter focuses on emergent aspects of echocardiographic evaluation of postinfarction LV remodeling in the setting of AMI treated by primary PCI.
First tertile
Second tertile
Third tertile 55% 49%
p
