EDUCATION IN HEART VOL 3 - PART 7 pot

NATIVE ATHEROSCLEROTIC LESIONS AND THE VESSEL WALL Selective coronary angiography depicts coronary arteries as a planar silhouette of the contrast filled lumen. Lesions are defined angiographically by the focal narrowing of the luminal silhouette. However, severe atherosclerosis may not lead to an apparent luminal stenosis if the atheroma affects the entire vessel segment (diffuse disease). Furthermore, as originally described by Glagov and colleagues, atheromatous disease may result in focal expansion of the vessel size (enlargement of the EEM), a process known as arterial remodelling. 3 IVUS has been extraordinarily useful in confirming these two phenomena (diffuse disease and remodelling) in vivo (figs 23.1 and 23.2). Diffuse disease The experience with transplant vasculopathy is a particularly striking demonstration of the angiographic underestimation of diffuse disease. Coronary transplant vasculopathy represents the major cause of death in the first year after transplantation. However, because the heart is denervated, post-transplant coronary obstruction does not lead to angina pectoris. Therefore annual surveillance angiography, with and without IVUS, is commonly performed in patients after cardiac transplantation. Comparative IVUS studies have demonstrated the insensitivity of angiography in detecting transplant vasculopathy. Angiographic disease is present in only 10–20% of patients at one year and in 50% by five years, while the prevalence of ar teriopathy detected by ultrasound is much higher, with abnormal intimal thickening seen by IVUS in 50% of patients by one year. 4 The diffuse involvement of entire coronary segments, which is characteristic for transplant vasculopathy, explains why this disease process does not lead to focal luminal narrowing and therefore is frequently not detected by angiography. Figure 23.1 Principle of IVUS transducer pullback. The transducer pullback through a vessel segment allows the assessment of adjacent image slices and the three dimensional reconstruction. Importantly, tomographic imaging with IVUS allows the assessment of the coronary arterial lumen and vessel wall. Therefore the atherosclerotic plaque can be directly visualised. The first IVUS panel (top left) shows a crescent of severe atheroma extending for most of the vessel circumference from the 10 o’clock position to the 7 o’clock position. This lesion has a faint (lucent) echo signal of a lipid rich core of atheroma with a more echogenic fibrous cap. Figure 23.2 Examples of adjacent IVUS images showing different plaque composition. In panel A, there is mainly fibrous composition to the plaque. In panel B, there are both fibrous and soft components to the plaque, with associated plaque ulceration and expansion of the vessel EEM, indicating positive remodelling at the site of severe narrowing. Panel C shows a large area of soft plaque with some calcification of the fibrous cap, indicated by the presence of acoustic shadowing of the image behind the calcification. EDUCATION IN HEART * 160 A similar process may go unrecognised in typical native vessel atherosclerosis. Several IVUS studies have shown that angiographically “nor mal reference sites” are frequently affected by atherosclerosis. 5 The angiographic finding of “small vessels”—for example, in diabetic patients—represents another extreme example of diffuse plaque accumulation without focal narrowing. Arterial remodelling Another important observation has evolved from IVUS examination of transplanted hearts. In some transplant centres, a baseline angiographic and IVUS examination of one or more coronary vessels has been performed routinely. This is typically performed within a few weeks following transplantation and thus reflects the state of the vessel at the time of donor death. Most transplant donor s are young in age, typically succumbing to trauma from motor vehicle accidents. Despite the young age of these donors, significant atherosclerosis is frequently detected by IVUS in donor coronary arteries. In one published study, more than half of donors at a mean age of 32 years had at least one site with an intimal thickness exceeding 0.5 mm. 6 Strikingly, nearly all of these subjects had completely normal angiograms. The finding of diffuse or focal lesions without angiographic stenosis perplexed cardiolog ists who viewed diseased coronary arteries as “rusty pipes”. In a solid pipe, accumulation of debris should always lead to a decreased luminal diameter. However, it seems clear that this paradigm is not appropriate in coronary arteries. In 1987 the pathologist Seymour Glagov described a crucial observation about early atherosclerotic lesion development. 3 Based on previous examinations in postmortem and animal models, Glagov described a positive correlation between EEM area and atheroma area in necropsy specimens of human postmortem arteries. The author hypothesised that focal disease is often not evident as luminal obstruction because of “compensatory” expansion of the vessel wall (arterial remodelling). Specifically, lesions with a stenosis < 40% were counterbalanced by an increase in arterial size that “compensated” for plaque accumulation, maintain- ing lumen area. In advanced lesions, remodelling was less evident and lumen size was reduced. IVUS has allowed the in vivo study of remodelling. Ultrasound studies confirmed the correlation between EEM and plaque area and compensatory vessel enlargement or “positive remodelling” in early disease. 7 Subsequent IVUS studies have demonstrated a new dimension to arterial remodelling, negative remodelling or arterial shrinkage. 8 At diseased sites, the EEM may actually shrink in size, contribut- ing to luminal stenosis. Initially described in restenotic lesions after coronary intervention, negative remodelling can also be found in mildly stenotic lesions of native coronary arteries. Our understanding of the central role of remodelling in the pathophysiology of CAD is evolving. Initially positive remodelling was seen as merely compensatory, and therefore a welcome “positive” process. However, recent IVUS studies examining the relation between remodelling and clinical presentation in patients with CAD suggest a more complex role. In unstable patients, both EEM and plaque areas were significantly larger than the corresponding measurements in stable patients. In other words, positive remodelling is significantly more prevalent in the unstable patients and negative remodelling more prevalent in the stable patients. 9 Lesion development and, in particular, lesion stability appear to be related to the direction of arterial remodeling. TheinitialexperiencewithIVUSshowedthatthesimulta- neous assessment of lumen and vessel wall could provide important insights into lesion development and significance. It was soon discovered that these principles also apply to lesion response during coronary interventions (figs 23.3, 23.4, and 23.5). Figure 23.3 Clinical application of IVUS. Figures 3–5 show images obtained from a 26 year old patient, who presented three months after stent deployment in the LAD for severe CAD. This fig shows the selective coronary angiogram of the previously stented LAD lesion. A focal expansion of the lumen at the proximal stent edge is visible. The silhouette of the angiogram does not define the anatomy of such non-obstructive lesions. UNDERSTANDING CORONARY ARTERY DISEASE: TOMOGRAPHIC IMAGING WITH INTRAVASCULAR ULTRASOUND * 161 PERCUTANEOUS CORONARY INTERVENTIONS Restenosis IVUS has shaped our understanding of restenosis after coronary percutaneous intervention. Initially, investigators believed that the predominant mechanism of restenosis after balloon angioplasty was intimal proliferation. However, ultrasound studies in peripheral vessels provided evidence that negative remodelling, or localised shrinkage of the vessel, was a major mechanism of late lumen loss. 8 Mintz and colleagues studied 212 native coronary arteries in patients undergoing repeat catheterisation after coronary interventions. At follow up, there was a decrease in EEM area and an increase in plaque area at the target lesion. 10 Interestingly, more than 70% of lumen loss was attributable to the decrease in EEM area, whereas the neointimal growth accounted for only 23%. Moreover, the change in lumen area correlated more strongly with the change in EEM area than with the change in plaque area. Lesions with an increase in EEM area at follow up (47% of segments studied) showed no change or an actual gain in lumen area and a reduction in angiographic restenosis (26% v 62%, p < 0.0001). These and other studies have established the role of negative remodelling in restenosis after mechanical intervention and explained the success of the concept of additional stenting in an attempt to prevent negative remodelling. Stenting IVUS has provided key insights into the reduction of restenosis rate observed with coronary stenting in compar ison to balloon angioplasty. In serial IVUS studies of stented coronary segments, no significant change occurred in the area bound by stent struts, indicating that stents can resist the arterial remodelling process and that stent restenosis is primarily caused by neointimal proliferation. The prevention of negative remodelling, combined with the greater initial lumen expansion with stenting, results in a lower net restenosis rate. However, during the initial clinical experience with stent implantation, acute stent thrombosis limited application to a relatively narrow subset of patients and required routine use of warfarin. Here, again, IVUS imaging played a pivotal role in optimising clinical results. The pioneering observations of Figure 23.4 An IVUS interrogation of this segment shows a dissection of the vessel wall extending beyond the stent struts. In the video sequences flow was evident in the dissection cavities. The close proximity to the epicardium is obvious and influenced the decision to intervene. Figure 23.5 In panel A, the left anterior descending (LAD) artery appears normal on the angiogram, yet on IVUS there is a clear crescent of soft atheromatous plaque. Similarly in panels C and C′ there is a severe concentric plaque indicating significant luminal narrowing. On angiography, at this point, there is a tubular narrowing as seen by IVUS. In panel B, the presence of the covered stent is seen with good and uniform stent expansion and a good angiographic result. EDUCATION IN HEART * 162 Colombo and colleagues, based upon IVUS, dramatically changed clinical practice. 11 These and other investigators showed that stent deployment with conventional balloon pressures resulted in a high incidence of incomplete stent expansion and poor apposition. In a pivotal series, Colombo and colleagues used IVUS imaging to guide high pressure dilatation, achieving full expansion and complete stent apposition in 96% of 359 consecutive, but non-randomised, patients. Patients with optimal expansion received antiplatelet treatment using aspirin and ticlopidine, but not warfarin. These technical modifications resulted in outstanding clinical outcomes. The incidence of acute and subacute stent thrombosis was less than 1%, and target vessel revascularisa- tion for symptomatic restenosis at six months was 13%. Thereafter, the concept of high pressure stent deployment disseminated rapidly, and larger trials demonstrated the safety of stent implantation using high pressures and antiplatelet treatment alone (without IVUS guidance). Consistent with these later trials, IVUS is no longer routinely used for stent optimisation. However, as newer interventional approaches are developed, IVUS imaging is routinely applied early in the life cycle of these innovations, often providing crucial insights into the mechanisms of benefit or complications. Accordingly, IVUS imaging is cur rently playing an important role in understanding the effects of radiation therapy for in-stent restenosis (brachytherapy), and the effects of drug eluting stents. ATHEROMA BURDEN AND VULNERABILITY It is not uncommon to see a young, previously healthy patient present with a massive myocardial infarction as the first manifestation of CAD. Despite great advances in the acute and chronic management of such patients, these cases demonstrate our failure to make the diagnosis of CAD in time to prevent serious complications. Traditional angiographic methods for assessing atherosclerotic disease rely exclusively upon the identificationofsignificantluminalstenosesasamarkerfor disease burden. However, IVUS and histological studies show that “significant” stenoses represent only a small fraction of the total atheroma burden in patients with CAD (fig 23.5). 12 Presumably, patients with major, unheralded coronary events lack sufficient luminal narrowing to result in exertion ischaemia. In this setting, the acute event originates from rupture of a non-stenotic, clinically “silent” atheroma. Epidemiolog ical data strongly support this model—several angiographic studies have documented that the majority of patients with acute myocardial infarction previously had only low grade stenoses at the culprit lesion site. Because most acute coronary events are initiated from unheralded rupture of such subclinical “vulnerable” plaques, it is not surprising that angiography provides limited predictive value in identifying the risk of subsequent coronary events. 13 Currently, the best predictors of future events are established clinical and biochemical risk factors including age, sex, history of diabetes mellitus, hyperlipidemia, f amily history, and inflammatory markers. However, intracoronary ultrasound offers significant potential as a means to identify and charac- terise “non-stenotic” coronary atheroma burden, and plaque vulnerability. This approach may allow development of new strategies for interventions (medical or mechanical) by targeting atheromas at risk of rupture. Two strategies are being actively pursued: the assessment of focal plaque vulnerability and quantification of diffuse overall atheroma burden. Focal plaque vulnerability Plaque vulnerability describes the tendency of atherosclerotic lesions to cause atherothrombotic complications. It is well established that most acute coronary syndromes are caused by the sudden rupture or superficial erosion of an atherosclerotic plaque. 12 The histology of these unstable plaques often reveals a lipid laden atheroma with a thin fibrous cap. A cascade of inflammatory processes probably plays a central role in the development and rupture of these lesions. 12 13 IVUS can demonstrate certain morpholog ic characteristics associated with plaque instability, including the necrotic, lipid rich core, the fibrous cap, and plaque rupture (fig 23.2). 14 15 More recently, studies have demonstrated a strong association between positive remodelling (enlargement of the EEM) and an unstable clinical presentation (acute myocardial infarction or unstable angina). We examined 85 patients with unstable and 46 patients with stable coronary syndromes using IVUS and found positive remodelling significantly more frequent in unstable than in stable lesions (51.8% v 19.6%), while negative remodelling was more frequent in stable lesions (56.5% v 31.8%) (p = 0.001). 9 It is an attractive hypothesis that atheroma inflammation associated with lipid deposition, characteristic of unstable lesions, causes both plaque rupture and vessel expansion. A fibrotic response associated with plaque healing may be associated with negative remodeling. 16 Diffuse overall plaque burden Recent studies demonstrate that plaque vulnerability, plaque rupture, and subsequent plaque stabilisation are highly dynamic and widespread processes. 17 Subclinical plaque rupture and subsequent healing frequently occur during the development of atherosclerotic lesions and may be a common mode of disease progression. It is therefore an attractive hypothesis that the total plaque burden may be related to the propensity to develop morbid complications of CAD. This is supported by the experience with calcium quantification using computed tomography. Although calcium scoring only quantitates the calcified component of the overall plaque burden, a correlation between the calcium score and clinical events has been consistently demonstrated. In addition, pharmacological studies have suggested a decreased rate of calcium score progression during lipid lowering treatment. 18 IVUShasgreatpotentialasameanstoquantifytheoverall extent of atherosclerotic disease burden. IVUS imaging in patients with limited angiographic CAD typically demonstrates a large disease burden, often showing atherosclerosis in every cross section. Results from a serial IVUS study with measurements of plaque burden as the primary efficacy parameter have recently been reported. 19 Large serial IVUS Key points c Tomographic imaging of coronary arteries with intravascular ultrasound (IVUS) demonstrates that simultaneous assessment of lumen and vessel wall can provide important insights into atherosclerotic lesion development and significance c Important principles described with IVUS—diffuse disease distribution and arterial remodelling—apply to native coronary artery disease (CAD) and lesion response during percutaneous coronary interventions c The insights previously obtained with IVUS can be applied during interventional treatment of significantly stenotic lesions c The examination of mildly stenotic lesions may allow an assessment of disease burden and plaque vulnerability and may become important for CAD prevention UNDERSTANDING CORONARY ARTERY DISEASE: TOMOGRAPHIC IMAGING WITH INTRAVASCULAR ULTRASOUND * 163 studies are currently underway examining the effects of different lipid lowering regimens and alternative antihypertensive agents on plaque burden. The results from these stud- iesmayfurtherdefinetheroleofIVUSintheassessmentof CAD progression or regression and the observation of the transition from stable “silent” disease to acute coronary syndromes. IVUS represents the first tomographic coronary image technique allowing the assessment of the intramural structures of the vessel wall. However, non-invasive imaging modalities, in particular multi-slice computed tomography and magnetic resonance imaging, are under development for clinical coronary artery imaging. 20 These non-invasive techniques have particular appeal in a setting of prevention, where the invasive nature of IVUS is a distinct disadvantage. The future cardiologist will use a broadened diagnostic armamen- tarium to identify a wide range of obstructive and non- obstructive forms of CAD. In addition to the identification and treatment of highly stenotic lesions, which already cause clinical disease, new emphasis will be placed on the identification of “silent” non-obstructive lesions in accord- ance with the Virschow triad. The systemic and local treatment of these developing lesions has the potential to prevent CAD progression and avoid morbid complications such as acute coronary syndromes. CONCLUSION The above discussion shows that tomographic imaging of coronary arteries with IVUS has significantly influenced our understanding of the pathophysiology and treatment of CAD. The comparison to angiography explains the complementary role of tomographic imaging of lumen and vessel wall and is exemplified in figs 23.3, 23.4, and 23.5. In this young patient with precocious CAD, IVUS guided the therapeutic, interventional approach of the non-obstructive left anterior descending artery lesion. On the other hand IVUS allowed surprising insights into the disease process by showing extensive, diffuse disease in an angiographically relatively unsuspicious coronary segment. We believe that tomographic coronary imaging with IVUS and emerging non-invasive modalities can contribute to an early diagnosis of subclinical CAD. It is an attractive hypothesis that this information could lead to improved preventive strategies. REFERENCES 1 Mintz GS, Nissen SE, Anderson WD, et al . American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS). J Am Coll Cardiol 2001;37:1478–92. c This ACC/AHA guideline paper gives a complete overview over procedural details of IVUS. 2 Nissen SE, Yock P. Intravascular ultrasound: novel pathophysiological insights and current clinical applications. Circulation 2001;103:604–16. c This review article summarises clinical applications of IVUS. 3 Glagov S, Weisenberg E, Zarins C, et al . Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316: 1371–5. c This seminal article describing arterial remodelling in human coronary arteries has changed our understanding of CAD. 4 Tuzcu EM, Kapadia SR, Tutar E, et al . High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound. Circulation 2001;103:2705–10. c This article describes the frequent presence of atherosclerotic lesions in young persons who died from non-cardiovascular causes. 5 Mintz GS, Painter JA, Pichard AD, et al . Atherosclerosis in angiographically “normal” coronary artery reference segments: an intravascular ultrasound study with clinical correlations. J Am Coll Cardiol 1995;25:1479–85. 6 Tuzcu EM, Hobbs RE, Rincon G, et al . Occult and frequent transmission of atherosclerotic coronary disease with cardiac transplantation: insights from intravascular ultrasound. Circulation 1995;91:1706–13. 7 Losordo DW, Rosenfield K, Kaufman J, et al . Focal compensatory enlargement of human arteries in response to progressive atherosclerosis: in vivo documentation using intravascular ultrasound. Circulation 1994;89:2570–7. 8 Pasterkamp G, Wensing PJ, Post MJ, et al . Paradoxical arterial wall shrinkage may contribute to luminal narrowing of human atherosclerotic femoral arteries. Circulation 1995;91:1444–9. 9 Schoenhagen P, Ziada K, Kapadia SR, et al . Extent and direction of arterial remodeling in stable versus unstable coronary syndromes: an intravascular ultrasound study. Circulation 2000;101:598–603. c One of the first articles describing the association between direction of remodelling and clinical presentation. 10 Mintz GS, Kent KM, Pichard AD, et al . Contribution of inadequate arterial remodeling to the development of focal coronary artery stenoses: an intravascular ultrasound study. Circulation 1997;95:1791–8. 11 Colombo A, Hall P, Nakamura S, et al . Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation 1995;91:1676–88. c This clinical series influenced the contemporary practice of stenting. 12 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990’s. Nature 1993;362:801–9. c Classical review of CAD which changed the concept of this disease. 13 Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001;104:365–72. c A concise review of current concepts about acute coronary syndromes. 14 Yamagishi M, Terashima M, Awano K, et al . Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome. JAmColl Cardiol 2000;35:106–11. c The first prospective IVUS study defining characteristics of mildly stenotic lesions which subsequently cause acute coronary syndromes. 15 von Birgelen C, Klinkhart W, Mintz GS, et al . Size of emptied plaque cavity following spontaneous rupture is related to coronary dimensions, not to the degree of lumen narrowing. A study with intravascular ultrasound in vivo. Heart 2000;84:483–8. 16 Burke AP, Kolodgie FD, Farb A, et al . Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 2002;105:297–303. 17 Goldstein JA, Demetriou D, Grines CL, et al . Multiple complex coronary plaques in patients with acute myocardial infarction. N Engl J Med 2000;343:915–22. c This article describes the frequent finding of additional complex angiographic lesions distant from the culprit lesions in patients presenting with acute myocardial infarction. 18 Callister TQ, Raggi P, Cooil B, et al . Effect of HMG-CoA reductase inhibitors on coronary artery disease by electron-beam computed tomography. N Engl J Med 1998;339:1972–8. 19 Schartl M, Bocksch W, Koschyk DH, et al . Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease. Circulation 2001;104:387–92. 20 Schroeder S, Kopp AF, Baumbach A, et al . Non-invasive characterization of coronary lesion morphology by multi-slice computed tomography: a promising new technology for risk stratification of patients with coronary artery disease. Heart 2001;85:576–7. EDUCATION IN HEART * 164 24 ROLE OF ECHOCARDIOGRAPHY IN ACUTE CORONARY SYNDROMES Sally C Greaves T he term “acute coronary syndrome” covers a spectrum of presentations, from unstable ang ina through to ST segment elevation myocardial infarction. There have been remarkable changes in the management of these conditions in the past two decades. With increasing emphasis on early reperfusion and prevention of left ventricular remodelling, echocardiography is assuming a prominent role in this area. It is non-invasive and relatively cheap, and is an ideal portable imaging technique. Newer imaging modalities, including myocardial contrast echo for the assessment of perfusion, hold great promise. c TECHNICAL ASPECTS The first cardiac ultrasound machines displayed an ultrasound pulse versus depth on an oscilloscope screen. Incorporation of time as a dimension in the late 1960s converted this to a single line M mode display. M mode echocardiography is still in use, but has largely been supplanted by two dimensional (2D) echocardiography, 1 which was developed in the 1970s. In the 1980s, spectral and colour Doppler were developed. The Doppler principle allows determination of the velocity and direction of blood flow, enabling assessment of valvar disease, shunts, and diastolic function. Transoesophageal echocardiography (TOE) was also introduced in the 1980s; initial probes were uniplane but multiplane probes are now routinely used, and there has been progressive transducer miniaturisation. TOE is very safe, with a mortality of less than 1/10 000, 2 but not completely risk free (table 24.1) and should be performed by experienced physicians. It is relatively contraindicated in patients with oesophageal disease—for example, varices, stricture, oesophagitis, scleroderma— and may be hazardous in patients with severe coagulopathy or poor respiratory function; it is essential that the performing physician be aware of such conditions. Transthoracic echocardiography (TTE) and TOE are complementary techniques. While TOE avoids image degradation related to the chest wall and lungs, TTE may visualise anterior structures and the cardiac apex better. More windows for Doppler interrogation are available from TTE, and it is easier to make standard measurements. Both TTE and TOE are technically demanding procedures, and meticulous attention is required to ensure optimal images are obtained. One of the most important recent technological achievements has been the development of harmonic imaging, which greatly improves endocardial definition. 1 In conventional echocardiography, images are derived from ultrasound waves returned at the same frequency as the transmitted waves. However harmonic frequencies are also produced by the transmitted wave; in harmonic imaging, the machine uses the returning second harmonic to construct images. This improves image quality because there is less distortion of returned ultrasound waves (they are generated in the heart and only have to pass through tissue once), and few harmonics are produced close to the chest wall where many artefacts arise. Digital echocardiography is an important advance 3 of particular relevance to the coronary care unit. This is a process by which cardiac cycles are recorded in digital format rather than on videotape. It has huge practical advantages and is ideal for the temporal monitoring of left ventricular (LV) function as it enab les side by side high quality images to be quickly av ailab le at multiple stations. COMPLICATIONS OF ACUTE MYOCARDIAL INFARCTION Echocardiography is the mainstay of diagnosis of mechanical complications of myocardial infarction (MI), 4 and patients with unexplained haemodynamic deter ioration should be immediately evaluated. It is important to recognise that TTE and TOE are complementary, and that TTE performed by an experienced echocardiographer may make an immediate diagnosis. In critically ill patients, image acquisition may be difficult; in these circumstances, TOE is extremely helpful. Cardiac rupture Many LV ruptures cause sudden death. However rupture may be subacute, allowing time for intervention. Direct visualisation of the rupture is often difficult as it may be only a “slit” in the myocardium and the location of pericardial fluid may not correlate with the area of rupture. However, * 165 intrapericardial thrombus is often present (fig 24.1) and is very character istic. It is rare to show flow into the pericardium. When caused by abrupt intrapericardial haemor rhage, the characteristic echocardiographic signs of tamponade may be absent, and diagnosis may rest on the volume of fluid and the clinical context. An LV pseudoaneurysm forms when the rupture is contained, so that a cavity outside the LV develops lined by pericardium and often thrombus. This can be distinguished from a true aneurysm by an abrupt interruption in the LV wall (asopposedtothesmoothcurveofatrueaneurysm),a narrow neck, and low velocity bidirectional flow (fig 24.2A, B). Ventricular septal rupture Septal rupture may be difficult to distinguish clinically from mitral regurgitation (MR). From 2D echocardiography a discrete defect may be visible, but there may also be multiple serpiginous channels in the necrotic myocardium. The diagnosis can usually be made by TTE; experience is essential as the most useful views depend on the location of defect. Subcostal views are particularly useful in the critically ill, supine patient with inferior infarction (fig 24.3A). Small defects may not be visible but colour Doppler is very sensitive (fig 24.3B). Because these defects are often not discrete the degree of shunting may be difficult to evaluate. A large left–right shunt is characterised by hypercontractility of non- infarcted LV segments with a low LV stroke volume, high pulmonary artery flow velocities, and pulmonary hypertension. Posterior septal ruptures in particular tend to be complex and often associated with r ight ventricular infarction, which has an adverse prognosis. Papillary muscle rupture Papillary muscle rupture is the most serious mechanism of MR in acute infarction. It usually involves the posteromedial muscle which is perfused from the posterior descending artery, whereas the anterolateral muscle has blood supply from both diagonal and circumflex arteries. Rupture of a papillary muscle head causes severe MR; rupture of the entire trunk is generally fatal. Transthoracic echocardiography is often suboptimal in evaluation—views of the papillary muscles are often limited, the MR jet is eccentric, and colour Doppler is influenced by the low LV/LA gradient in acute severe MR. TOE is a particularly suitable imaging modality 4 andshouldbeperformedimmediatelyifthisdiagnosisis suspected—it provides high resolution images of the papillary muscles (fig 24.4A) and accurate assessment of MR. Rarely, multiple catastrophic mechanical complications of MI may occur in the same patient (figs 24.3A and 24.4A, B). Aneurysm formation and left ventricular thrombus True aneurysms complicate transmural infarction and are caused by dilatation of an area of scar (fig 24.5). An aneurysm is defined as deformation of both the diastolic and systolic LV contours with dyskinesis in systole. TTE is a sensitive tool for the diagnosis but occasional false negatives occur, usually whentheaneurysminvolvesasmallpartoftheapexorthe Table 24.1 Potential complications of transoesophageal echocardiography c Respiratory depression c Hypotension c Arrhythmias c Laryngospasm/bronchospasm c Dental trauma c Pharyngeal/oesophageal/gastric trauma and perforation c Aspiration c Displacement of ET/nasogastric tubes c Death ET, endotracheal. Figure 24.1 Subcostal long axis transthoracic image showing a pericardial effusion (PE) and intrapericardial thrombus (arrow) in a patient with left ventricular rupture post-infarction. LV, left ventricle; RV, right ventricle. Figure 24.2 (A) Parasternal short axis transthoracic image showing a pseudoaneurysm of the inferior wall. The arrows show the characteristic abrupt disruption of the inferior wall and a narrow neck leading to the pseudoaneurysm. (B) Parasternal short axis transthoracic image (same patient as in A) showing bidirectional flow (arrows) from colour Doppler. Ant, anterior left ventricular wall, RV, right ventricle. PA, pseudoaneurysm. EDUCATION IN HEART * 166 basal anterolateral wall. Aneurysm formation is a poor prognostic sign and is associated with congestive cardiac failure, arrhythmias, and thrombus for mation. Left ventricular thrombi form in regions of stasis; they most commonly occur in the apex (fig 24.5) but may also be seen in lateral and inferior aneurysms. Certain echocardiographic characteristics (pedunculated and mobile thrombi) are associated with higher risk of embolisation. 5 TOE may not visualise the apex as well as TTE. Pericarditis Echocardiography is a sensitive technique for the diagnosis of pericardial effusion; however the absence of fluid does not exclude per icarditis. In patients who are anticoagulated, intrapericardial thrombus may be recognised. Echocardiography can identify a site for percutaneous drainage if required and be used to monitor the procedure. Right ventricular infarction Recognition of right ventricular (RV) infarction is important, as it requires specific haemodynamic management. This syndrome occurs in more than 30% of patients with inferior MI butisrareinanteriorinfarctionandinisolation.Manyright coronary artery occlusions do not result in significant RV infarction due to the lower RV oxygen demand, higher oxygen extraction ration, greater systolic/diastolic flow ratio, and col- lateral supply. Right ventricular infarction may be diagnosed clinically and from right sided ECG leads, but echocardiography provides better assessment of the extent and sever ity. 6 Right ventricular dysfunction may be global or regional; the Figure 24.3 (A) Subcostal long axis transthoracic image showing a large post-infarction rupture (arrow) in the mid inferior ventricular septum (IVS). (B) Apical four chamber transthoracic image showing colour Doppler flow (arrow) through a postinfarction apical ventricular septal defect. LA, left atrium; LV, left ventricle; RV, right ventricle. Figure 24.4 (A) Transgastric image showing rupture of the posteromedial papillary muscle postinfarction. The arrows point to the separated portions of the trunk of the papillary muscle. (B) Transoesophageal image (same patient as in A) showing pronounced flow convergence from colour Doppler (arrow) as flow accelerates towards a regurgitant orifice; this is characteristic of severe mitral regurgitation. PMVL, posterior mitral valve leaflet; INF, inferior LV wall; ANT, anterior LV wall; LV, left ventricle; LA, left atrium. Figure 24.5 Apical four chamber transthoracic image showing extensive thrombus in an apical aneurysm. TH, thrombus; LV, left ventricle; LA, left atrium. ROLE OF ECHOCARDIOGRAPHY IN ACUTE CORONARY SYNDROMES * 167 RV outflow tract and apex are often spared, and hypercontractility in these regions may be a diagnostic clue. Echocardio- graphy can evaluate complications of RV infarction. Func- tional tricuspid regurgitation is common; rarer complications are papillary muscle rupture and hypoxaemia from shunting through a patent foramen ovale caused by raised RA pressure. RISK STRATIFICATION IN THE CORONARY CARE UNIT Echocardiography is of tremendous value in risk stratification in MI and unstable angina. In general, it is helpful for these patients to have assessment of LV function before angiography. Echocardiography can provide a non-invasive biplane assessment, identify unsuspected valvar abnormalities, and evaluate right heart function. Left ventricular angiography may not be appropriate in critically ill patients and it is easier to obtain accurate information before invasive testing. Patients with unstable angina and non-ST segment elevation MI are a heterogeneous group. Risk stratification is particularly relevant if conservative management is planned. Those patients with persistent wall motion abnormalities have more severe, chronic ischaemia and are at higher risk of adverse events. 7 All patients with acute MI should ideally have early echocardiography. In some patients it may assist in diagnosis; it may also assist decision making if the appropriateness of reperfusion is uncertain, by demonstrating the localisation and extent of wall motion abnormality. Echocardiography is particularly important in those patients who are not obviously high risk; many patients without clinical evidence of LV dysfunction will have significant wall motion abnormalities. 7 Patients with extensive regional abnormalities should have follow up echocardiography—this may detect early LV remodelling and other complications, and affect subsequent medical management. Multiple indices of LV systolic and diastolic function have predictive value post-MI. Left ventricular wall motion score index(WMSI)isobtainedbygradingthemotionof myocardial segments based on a standard model (table 24.2). It is par ticularly appealing, as while significant experience is required to interpret wall motion, it is highly reproducible. It reflects LV ejection fraction, but not LV size, so that quantita- tive measurements are also helpful. Left ventricular ejection fraction, 7 end systolic volume, 7 WMSI, 8 and the presence of even mild MR 9 are all early predictors of adverse outcome. Severe LV diastolic dysfunction tends to be associated with large inf arctions, but a restrictive pattern is also independ- ently associated with poor outcome. 10 Although there are numerous factors which can alter filling patterns, Doppler echocardiography is very repeatable. The Doppler myocardial performance index is a more recently developed measurement combining indices of systolic and diastolic function. 11 Re- peated echocardiographic measurements have particular value, 12 as they reflect LV remodelling, characterised by altera- tions in LV size, shape, and wall thickness. Remodelling may initially be compensatory in that it helps maintain LV stroke volume, but it progressively leads to increased LV wall stress, further dilatation, and eventually deleterious effects. Early remodelling and LV aneurysm formation is a particularly poor prognostic sign. Three dimensional echocardiography is more accurate than 2D echocardiography in the assessment of LV size and shape and may have a particular role in the evaluation of LV remodelling. It is a gold standard in research and is now coming into more routine clinical use, although the work involved in data acquisition and image reconstruction remains significant. There are many newer techniques that can be utilised for evaluation of LV function and ischaemia, including tissue Doppler imaging, strain rate imaging, and tissue characterisa- tion; the discussion of these is beyond the scope of this review. Stress echocardiography has an important role post-MI. Although some centres use a stress imaging modality routinely post-MI, standard treadmill testing is adequate for many patients. Exercise echocardiography is appropriate for patients who can walk on a treadmill. Pharmacological stress echoisindicatedprimarilyinpatientsunabletoexercise adequately for non-cardiac reasons and for assessment of viability. ECHOCARDIOGRAPHY IN THE EMERGENCY ROOM AND CHEST PAIN UNIT The potential use of echocardiography for diagnosis of MI is based on observations of the effects of interruption of coronary flow. Left ventricular diastolic dysfunction occurs before systolic dysfunction; ECG abnormalities and chest pain are relatively late events. Segmental wall motion abnormalities seen by echocardiography correspond closely with coronary artery territories, although there is some variation depending on dominance of the right coronary artery and circumflex arteries and extent of “watershed” areas. Optimal use of any diagnostic technique needs review of its cost effectiveness and impact on decision making, and use should always depend on the availability of resource and expertise. Sensitivity and specificity are inversely related; which is most important depends on the implications of miss- ing the diagnosis versus making an incor rect diagnosis. Sensi- tivity and specificity are influenced by the pretest likelihood of disease (Bayes theorem). These are important considerations in examining the role of echocardiography in the emergency room as this is a much less selected patient group than in the coronary care unit. The problem is both economic and medico-legal. Many patients admitted with chest pain do not have an acute coronary syndrome whereas 5–10% of those who do are discharged. The challenge is to identify low risk patients without compromising the care of higher risk patients; the latter consideration is particularly relevant given the importance of early reperfusion. Chest pain units linked to the emergency room are an important approach to improving thequalityandefficiencyofcareforthesepatients,with emphasis not only on reducing costs but on improving early diagnosis and triage to effective management. There are many studies of echocardiography for MI diagnosis. 13 14 Some are in small, highly selected groups but most have found similar diagnostic sensitivity (approximately Table 24.2 Qualitative scale for derivation of the echocardiographic wall motion score index Score* Wall motion Definition 0 Hyperkinetic Increased endocardial inward movement and systolic wall thickening 1 Normal Normal endocardial inward movement and systolic wall thickening 2 Hypokinetic Reduced endocardial inward movement and systolic wall thickening 3 Akinetic Absence of endocardial inward movement; no systolic wall thickening 4 Dyskinetic Outward wall movement in systole with absent wall thickening; often associated with myocardial thinning and fibrosis *The score for each segment is divided by the number of segments visualised to obtain the wall motion score index. EDUCATION IN HEART * 168 90–95%). The negative predictive value is high (approximately 95%), but the positive predictive value is much lower and more variable. 14 This may partly relate to interpretation difficulties in the presence of prior infarction, and aggressive interpretation of minor abnormalities by physicians anxious to avoid false negatives. From these studies, echocardiography appears more sensitive than standard criteria for the diagnosis of infarction; it is also sensitive for the diagnosis of myocardial ischaemia, but only if performed during pain. Echocardio- graphy provides incremental prognostic information in the identification of patients at risk of cardiac events. However, if echocardiography is used alone, a small number of patients with subendocardial infarction will be discharged. The study by Trippi and colleagues 15 is an example of how echocardiography might be aggressively used in the emergency room. These authors enrolled 163 patients with no evidence of MI on initial cardiac markers or ECG, who were rec- ommended for admission. If rest echocardiographic images were normal, dobutamine stress echocardiography was performed, initially supervised by a cardiologist and, in later stages, by a trained nurse. Echocardiographic images were transmitted by tele-echocardiography and interpreted off-site. In the first three stages, all patients were admitted. In the final stage, patients were discharged if the stress echocardiogram was negative. Average length of stay was only 5.4 hours. In the third and fourth stages recruitment was less selective, so that in the final phase mild residual chest pain, a non-diagnostic rather than normal ECG, and mild elevation of initial creatine kinase (CK) with normal CK-MB were permitted. The negative predictive value of dobutamine stress echocardiography was 98.5% based on final diagnosis, which was largely based on clinical follow up. There were two false negative results—one in a patient who was admitted in the third stage but discharged without a clinical diagnosis, and one in a patient who was discharged following a normal stress echocardiogram. The study is interesting because of the aggressive approach to achieving discharges, the use of tele-echocardiography and nursing supervision to avoid having a cardiolog ist on-site, and the choice of pharmacological stress to avoid the noise of a treadmill and the requirement for patient cooperation with exercise. However, most authors would argue that MI should be fully excluded by ser ial markers and ECGs, and that there be complete resolution of chest pain before stress testing. In summary, echocardiography in the emergency room may facilitate early diagnosis and management in those patients withahighclinicalsuspicionofMIbutanon-diagnosticECG. Itmayalsodiagnoseunstableanginaifperformedduring pain. Aggressive use of rest and stress echocardiography can reduce admissions, but some false negatives will occur and small subendocardial infarctions may not be detected. These patientsmaybeatalowerriskofcomplicationsbutdataon this are limited. False positives will also occur and differentia- tion of ischaemia from old infarction may be difficult; this is not of major importance, given that these patients are likely to be admitted. The chief logistical difficulty is the necessity for experienced staff and expensive equipment on a 24 hour basis. Hand held, battery powered echocardiographic devices are now available. 16 In many emergency rooms these devices are routinely used (a popular option as it avoids having to call the echocardiography laboratory); they are also used on ward rounds as “ultrasound stethoscopes” and for teaching. Studies show that they are more accurate than physical examination. However, they have limitations that can result in significant errors; Doppler functions on these devices are substantially inferior to the 2D imaging, although the quality will undoubt- edly continue to improve. The optimal use of these devices and the implications for training and medicolegal issues remain controversial. CONTRAST ECHOCARDIOGRAPHY First generation contrast agents such as agitated saline have been available for many years and are still useful for detection of intracardiac shunts. However these agents do not opacify the LV, as the bubbles cannot survive passage through the lungs. Second generation contrast agents 17 incorporate high molecular weight gases which are more stable and can traverse pulmonary capillaries. Microbubble properties depend on bubble size, shell composition, and the gas used. When harmonic imaging is used, contrast agents achieve RVandLVopacificationwithimprovedimagequalityand reviewer confidence, 17 and are of particular value in technically challenging subjects. They can also be used to enhance spectral Doppler signals; in patients with acute MI, they can occasionally be of value in other situations—for example, detection of myocardial rupture and LV thrombus. Abbrevations CK: creatine kinase 2D: two dimensional LV: left ventricular MCE: myocardial contrast echocardiography MI: myocardial infarction MR: mitral regurgitation RV: right ventricular TIMI: thrombolysis in myocardial infarction TOE: transoesophageal echocardiography TTE: transthoracic echocardiography WMSI: wall motion score index Echocardiography in acute coronary syndromes: key points c Transthoracic and transoesophageal echocardiography are complementary techniques with different strengths c Transoesophageal echocardiography is very safe, but does have potential complications and should be performed by experienced physicians c Hand held cardiac ultrasound devices are likely to be increasingly used in both the emergency room and coronary care unit but remain controversial c Echocardiography for diagnosis of myocardial infarction is most helpful in patients with a high clinical suspicion but a normal or non-diagnostic ECG c Patients with unexplained haemodynamic deterioration postinfarction should be referred immediately for echocardiography c Echocardiographic indices of left ventricular systolic and diastolic function provide prognostic information in unstable angina and myocardial infarction c Contrast echocardiography for left ventricular opacification may be helpful in the evaluation of cardiac function in “technically difficult” subjects c Myocardial contrast echocardiography can evaluate the success of reperfusion and assess myocardial viability c Intravenous myocardial contrast echocardiography is likely to become a routine clinical tool ROLE OF ECHOCARDIOGRAPHY IN ACUTE CORONARY SYNDROMES * 169 [...]... recommendations for targeting of antihypertensive treatment by the British Hypertension Society4 is shown in fig 26.4 REFERENCES 1 Anderson KM, Odel PM, Wilson PWF, et al Cardiovascular disease risk profiles Am Heart J 1991;121:2 93 8 c This paper contains the Framingham risk functions 2 Ramsay LE The hypertension detection and follow-up program 17 years on JAMA 19 97; 277 :1 67 70 c A discussion outlining how absolute... frequency imaging However, higher imaging frequencies are also prone to greater tissue attenuation and so the jets may appear smaller In general, for transoesophageal imaging the Doppler enhancing effect of the higher imaging frequency dominates while for transthoracic imaging the attenuation factor predominates, causing jets to appear smaller at higher interrogating frequencies Increasing the wall... can be divided into two broad areas—volumetric assessment and direct assessment The volumetric assessment relies on measuring stroke volume in two regions of the heart, one of which includes the regurgitant volume, the other of which includes only the systemic stroke volume.5 The difference between these two stroke volumes is the regurgitant volume through the valve (fig 25.2) For example, in the case... Aliasing radius: r 60 ml * 40 ml Qv 0 174 -4 2 100 ml Flow: Q Orifice vel: v0 Figure 25.2 The principle of the volumetric assessment of valvar regurgitation By measuring stroke volume in two areas of the heart, it is possible to use the difference between these to estimate regurgitant volume Qs, systemic stroke volume; Qv, stroke volume across regurgitant valve; RV, regurgitant volume and time.6 7 Such... uncertainty rises even more, since the denominator (the regurgitant volume) is so much smaller For example, if we assume that mitral and aortic stroke volume can be measured with approximately 15% accuracy (not a bad accuracy), we might obtain the following sample calculations: aortic stroke volume, 70 (10) ml; mitral stroke volume, 100 (15) ml; mitral regurgitant volume, 30 (18) ml, indicating that... echocardiography in acute myocardial infarction: time to test for routine clinical use? Heart 1999;81:2–5 c This is an editorial linked to a study of intracoronary myocardial contrast echocardiography However, it is written by an international expert in this field, and provides an insightful view into the possible use of myocardial contrast echocardiography in the management of acute myocardial infarction 171 *... echocardiography in acute coronary syndromes including emergency department imaging Echocardiography 2000; 17: 479 – 93 This is an excellent review of the use of both rest and stress echocardiography in the emergency room It also has a good general review of the different modalities of stress echocardiographic testing and the relevant advances in imaging technology Trippi JA, Lee KS, Kopp G, et al Dobutamine stress... the future in echocardiography Heart 19 97; 78(suppl I):19–22 Kishon Y, Iqbal A, Oh JK, et al Evolution of echocardiographic modalities in detection of post myocardial infarction ventricular septal defect and papillary muscle rupture: study of 62 patients Am Heart J 19 93; 126 (3 Pt 1):6 67 75 This study reports a large series of patients with septal and papillary muscle rupture postmyocardial infarction... with continuous wave Doppler: ROA = Q/vmax This approach has been well validated in a number of experimental and clinical studies.9 It has advantages over the volumetric approach in that all measurements are obtained from a single imaging window, typically one of the apical windows, and the flow rate is measured directly, not requiring subtraction of two large quantities from each other as in the volumetric... rate 13 Sitges M, Jones M, Shiota T, et al Interaliasing distance of the flow convergence surface for determining mitral regurgitant volume: a validation study in a chronic animal model J Am Coll Cardiol 2001 ;38 :1195–202 c A new method for avoiding the problem of localising the regurgitant orifice by measuring the distance between the first two aliasing contours 14 Schwammenthal E, Chen C, Benning F, . concentrates primarily on clinical/legal issues. Physicians should become EDUCATION IN HEART * 170 familiar with the issues involved; this paper also provides insight into considerations arising with the introduction. patients and required routine use of warfarin. Here, again, IVUS imaging played a pivotal role in optimising clinical results. The pioneering observations of Figure 23. 4 An IVUS interrogation of this. crucial insights into the mechanisms of benefit or complications. Accordingly, IVUS imaging is cur rently playing an important role in understanding the effects of radiation therapy for in- stent

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