Acute effects of myocardial ischemia

Significant coronary artery stenosis results in impaired blood flow and reduced myocardial oxygen supply. When myocardial oxygen demand exceeds supply, myocardial ischemia develops. In addition, in the setting of a complete coronary artery occlusion, myocardial necrosis can occur. As a result of hypoxia, the myocardium shifts from aerobic oxidative phosphorylation to anaerobic metabolism. Consequently both fatty acid and carbohydrate oxidation decrease, ATP production is impaired, and glycolysis is accelerated, which requires increased uptake of glucose by the heart. ^, The glucose taken up by the ischemic myocardium is not readily oxidized in the mitochondria, but rather is converted to lactate, resulting in a fall in intracellular pH and a decrease in contractile work. Successful reperfusion of reversibly injured myocytes is associated with partial or complete restoration to the control state of many of the metabolic changes present in the ischemic myocytes and resumption of oxidative phosphorylation. ^,

Echocardiographic detection of myocardial ischemia and infarction

Echocardiographic detection of myocardial ischemia is based on visualizing a regional decrease in systolic endocardial motion and myocardial thickening. In the presence of a flow-limiting coronary lesion, the increased myocardial blood flow that normally occurs with physiologic stress is impaired, and this results in decreased regional systolic wall thickening, or hypokinesis. Similarly, with complete coronary ligation or acute obstruction, there is an immediate loss of normal myocardial contraction in the region supplied by the affected vessel followed by regional systolic bulging. With chronic coronary artery occlusion and infarction there can also be systolic thinning of the myocardium. Thus regional left ventricular (LV) wall abnormalities have become the hallmark of coronary artery disease and can be imaged on echocardiography. Studies in which progressive coronary stenoses are produced in animal models have shown a nearly linear correlation between regional wall motion (by sonomicrometry) and subendocardial blood flow, ^, suggesting that regional wall motion abnormality (WMA) is a sensitive marker of acute ischemic events. It has also been shown that with coronary occlusion, regional wall hypokinesis occurs earlier than the classic electrocardiographic changes. Other studies have shown that a fall in regional contraction of greater than 10% is a reliable marker of regional flow deficit and reflects a defect in subendocardial perfusion. Based on both experiments in dog models ^, and observations in humans during percutaneous coronary angioplasty, ^, an ischemic cascade has been postulated ( Fig. 48.1 ). As seen in this cascade, echocardiography allows for detection of WMAs at an earlier phase than the appearance of electrocardiographic (ECG) changes and clinical symptoms.

Diagram of the ischemic cascade demonstrating that localized left ventricular systolic dysfunction seen on echocardiography as a wall motion abnormality occurs before ECG changes and chest pain symptoms.

Experimental studies with graded coronary artery ligation to induce subendocardial ischemia indicate that, in addition to dysfunction of the ischemic zone, there is also a small zone of mild hypofunction immediately adjacent to the ischemic zone, with hyperfunction beyond that zone. ^, Studies have demonstrated that WMAs visualized with two-dimensional echocardiography exceed pathologic infarct size in acute infarction but can underestimate pathologic size in old infarction. This may reflect border-zone hypoperfusion, small islands of necrosis, or tethering of normal segments adjacent to abnormal segments. Wall thickening abnormalities on two-dimensional echocardiography can be detected when necrosis involves a small (1% to 20%) amount of the myocardial segment thickness. When more than 20% of the transmural thickness is infarcted, the segment demonstrates a constant degree of degradation in wall thickening, and there is not a further gradual deterioration in wall thickening for larger degrees of involvement of the myocardial thickness. Thus, in addition to the effects of mechanical tethering, wall motion abnormalities noted in the border zones of infarcts may reflect small amounts of necrosis.

Early experimental data showed that the resting coronary blood flow was not decreased until tight coronary stenosis greater than 90% developed. Systolic dysfunction and WMAs in the setting of physiologic stress are generally perceptible in coronary artery stenoses in the range of 50% to 60%; akinesis is seen when a reduction in coronary flow that is greater than 80% is present. ^,

The subjective assessment of LV wall motion by echocardiography requires the interpreter to integrate both endocardial motion and transmural wall thickening during systole. Although the wall motion may be easier to assess, it does not appear to differentiate regions of ischemia and infarction as well as wall thickening does. The wall thickening directly correlates with myofiber function, whereas endocardial motion is an end result of myofiber shortening. The perception of wall motion is also subject to the effects of translation and other extracardiac motions.

The major limitation to detection of both resting and stress-induced WMAs by echocardiography is the subjective nature of the assessment. In an effort to overcome this limitation, techniques that quantify various aspects of myocardial function, endocardial motion, and myocardial mechanics have been applied to echocardiography. To date, none of these parametric techniques have been integrated into clinical practice.

Patterns of ischemia based on coronary artery involvement

Clinical studies with two-dimensional echocardiography have demonstrated a clear relationship between the location and extent of WMAs and pathologic size of infarction. ^{, ,} Although there is some variability in the branching pattern of the coronary arteries supplying the various segments of the LV, location of wall motion is reproducibly linked to the affected artery. Ischemia or infarction due to disease in the left anterior descending coronary artery results in WMAs in the anterior and anteroseptal segments at the base, midlevels, and most or all of the apex. Ischemia or infarction due to disease in the right coronary artery results in WMAs in the inferior and inferoseptal segments at the base and mid LV. Ischemia or infarction due to disease in the left circumflex coronary artery results in WMAs in the lateral wall at the base and mid LV. The dominance of the coronary artery pattern will influence whether the right coronary artery or the circumflex coronary artery supplies the inferolateral segments. Likewise, the anterolateral territory can be supplied by either the left anterior descending coronary artery or the left circumflex coronary artery.

Detection of isolated left circumflex coronary artery disease by stress echocardiography is much more difficult than detection of isolated left anterior or right coronary artery disease. The sensitivity to detect stress-induced WMAs increases as the number of diseased vessels increases.

False indications of ischemia on echocardiography

Not all LV WMAs seen on echocardiography are due to myocardial ischemia or infarction. Other causes include septal WMAs due to left bundle block, right ventricular pacing, intrinsic conduction abnormality, postoperative changes, and right ventricular volume overload. In most of these situations, wall thickening will be preserved, although its timing may differ from normal. That is, motion is abnormal but thickening is normal. Nonischemic etiologies for cardiomyopathy and marked hypertension are other possible causes of WMAs. In these situations, thickening will be reduced. In the case of cardiomyopathy the wall motion can reflect disruptions to normal myocyte function or extensive myocardial fibrosis. Even in the absence of significant coronary artery disease, a marked increase in blood pressure sometimes noted during stress echocardiography can prevent the development of hyperkinesis or even result in global hypokinesis. Such findings are thought to be due to a sudden increase in myocardial oxygen demand under conditions when oxygen delivery cannot be increased because of the high pressure transmitted to the subendocardium directly from the LV cavity. False-positive WMAs perceived in the basal inferior or inferoseptal walls can be caused by off-axis imaging, poor endocardial visualization, and regional distortions in left ventricular shape, or false positives can represent regions where relatively thinner myocardium is perceived as hypokinetic. In the absence of prior heart surgery and hyperdynamic mid and distal segments, an isolated basal WMA during stress echocardiography is unlikely to reflect coronary artery disease.

Over the last 80 years, the effects of myocardial ischemia and infarction on the left ventricle have been well characterized. With its excellent temporal and spatial resolution echocardiography is an ideal modality for the assessment of the abnormalities of left ventricular wall motion and thickening that occur with infarction and ischemia.

Left ventricle

Evaluation of LV function and morphology, and regional wall motion and thickening can be critical in detecting ACS or cardiomyopathies.

Left Ventricular Function and Acute Coronary Syndrome

As an acute coronary event occurs, coronary flow through the vessel is impaired, resulting in myocardial ischemia. The coronary arteries are not properly visualized by echocardiography, therefore the focus is on imaging the myocardium. Classic findings in ACS include regional wall motion abnormalities (hypokinesis or akinesis) with impaired thickening of the affected myocardium. More recently, the use of microbubble contrast agents for myocardial perfusion imaging has also allowed the detection of ischemic myocardium in resting echocardiograms. As coronary artery disease affects the myocardium regionally, the distribution of such abnormalities respects the coronary territories. It should be noted, however, that coronary distribution varies among individuals and should only be used as a guide.

Although musculoskeletal pain is the most frequent cause of CP upon presentation to the ED, detecting ACSs is critically important, because administration of antiischemic therapies (including revascularization) must be adequate and timely. The presence of ST segment elevation on an ECG should trigger immediate coronary catheterization and intervention, therefore an echocardiogram should not delay such intervention and must be postponed until the procedure is finished. However, in cases of suspected ACS without ST elevation, an echocardiogram in the ED could be enormously valuable in detecting myocardial infarction (MI) and predicting cardiac events. Although cardiac biomarkers, particularly Tn and myoglobin, are extremely sensitive in detecting myocardial infarction, results of these tests may remain negative for a few hours after CP onset. On the other hand, echocardiographic findings (regional wall motion abnormality [WMA]) of myocardial ischemia are detected in almost 90% of patients scanned during or immediately after experiencing CP. A combined approach using Tn and echocardiogram has high accuracy in detecting ACS without ST elevation, with sensitivity and specificity over 90%. ^,

Patients with CP and left bundle branch block represent a particular challenge in that the abnormal ECG could be masking ST elevation. Although historically this has been an indication for emergent catheterization, the concept has been challenged and the use of biomarkers and bedside echocardiogram is now advocated to identify acute infarction: evidence of a hypokinetic or akinetic segmental WMA (lack of normal myocardial thickening in addition to myocardial excursion) in the anterior wall, in the absence of evidence of a prior infarction (wall thinning, chamber dilatation) should trigger an emergent catheterization. ^,

The utility of contrast echocardiography in the ED in identifying myocardial perfusion defects has been validated in several studies and reviewed in the recent American Society of Echocardiography (ASE) guidelines. In the setting of ischemia, typical findings are poor contrast uptake in the subendocardial myocardium ( Fig. 49.1 ). The addition of myocardial contrast echocardiography to regional function increased the diagnostic and prognostic value of patients with CP and no ST elevation in the ED, and proved to be a cost-effective intervention by facilitating early discharge of those with normal perfusion. Despite their promising potential, contrast agents for myocardial perfusion imaging have not yet been approved by the U.S. Food and Drug Administration.

Myocardial contrast echocardiography. This patient developed chest pain and left anterior descending (LAD) artery occlusion. The left panel is a two-chamber view showing perfusion defect (minimal bubble uptake) in the mid to apical segments of the anterior wall ( arrow ). The right panel reveals diffuse coronary disease with occlusion of the mid LAD artery ( arrow ).

Left Ventricular Function and Cardiomyopathies

In addition to ischemic cardiomyopathy, two other myocardial diseases can present with acute onset CP: myocarditis and takotsubo cardiomyopathy (apical ballooning syndrome). Myocarditis can present in a variety of forms, from small areas of WMA to global hypokinesis, and can be accompanied by pericardial effusion. Typically, these abnormalities do not respect a coronary territory, and frequently the wall motion pattern cannot be differentiated from that of other forms of dilated cardiomyopathies.

Takotsubo cardiomyopathy is a transient form of LV dysfunction in a characteristic pattern of apical ballooning: akinesis or dyskinesis, or both, of the apical half of the LV with normal or hyperdynamic basal segments ( Fig. 49.2 ). It affects mostly postmenopausal females and is triggered by emotional or physical stress. Although the course is generally benign and reverts within weeks, complications are not uncommon and include cardiogenic shock, ventricular tachycardia (torsades de pointes), atrioventricular block, apical thrombus, ventricular rupture, and LV outflow tract obstruction with systolic anterior motion of the mitral leaflets (see Fig. 49.2 ) and mitral regurgitation. More recently, atypical forms of takotsubo cardiomyopathy have been described, with other patterns of transient WMA triggered by stress. Importantly, apical ballooning could be indistinguishable from an anterior MI, and therefore cardiac catheterization is warranted to evaluate the left anterior descending artery.

Takotsubo cardiomyopathy (apical ballooning). A 62-year-old man with chest pain in the context of a recent stressful situation, exhibits ST depression in precordial leads and normal coronary arteries. The left panel shows a five-chamber apical view in systole with classical apical ballooning due to akinesia/dyskinesia of the apical half of the LV and normally contracting basal segments. The arrow points at systolic anterior motion of the anterior mitral leaflet, reflecting left ventricular outflow tract (LVOT) obstruction. The left panel is a continuous wave Doppler recording through the LVOT from the same window, with characteristic “dagger-shaped” spectral recording, reflecting a rapid gradual increase in the degree of obstruction as systole progresses.

Right ventricle

Pulmonary embolism (PE) is a critical differential diagnosis to be made in acute chest pain because specific urgent treatment is required. In rare occasions, the diagnosis of PE can be made with TTE by visualizing a thrombus in transit in the right-sided cardiac chambers or a saddle embolism in the main pulmonary artery in a high short-axis view of the great vessels ( Fig. 49.3 ). More frequently, however, indirect evidence of a PE on echocardiography includes signs of RV strain, such as RV dilatation and dysfunction. These echocardiographic findings are not specific but are sensitive in detecting large PE. A sign described by McConnell and colleagues (hypokinesis of the RV free wall with normally contracting apex) is more specific for acute RV dysfunction, which may be encountered in the setting of acute PE or RV infarction. Because RV infarction almost always presents with inferior MI, the lack of LV WMAs in the presence of McConnell sign is highly specific for PE.

Pulmonary embolism. A 55-year-old woman with history of deep vein thrombosis/pulmonary embolism and an inferior vena cava (IVC) filter had presenting symptoms of chest pain (CP), respiratory failure, and hypotension. The transthoracic echocardiogram (TTE) showed a severely dilated and dysfunctional right ventricle (RV), with RV pressure and volume overload. A, A flattened interventricular septum is visible during systole and diastole in a parasternal short-axis view. B, A large thrombus is present in the IVC, between the IVC filter and the right atrium (RA; on the right). C, A thrombus is in transit in the RA, as shown with TTE (subxiphoid view) in a different patient with presenting symptoms of dyspnea and CP.

Aorta

Acute aortic syndromes (aortic dissection, intramural hematoma, and ulcerated plaques) present as acute chest pain and represent medical emergencies. Therefore, although they are uncommon, their surveillance is critical when the clinical suspicion is present. The sensitivity of TTE for detection of aortic dissection is low because it is difficult to image the entire vessel, but sensitivity is high for the proximal ascending aorta. ^, However, when an echocardiogram for acute chest pain is being performed, several findings should indicate the possibility of aortic dissection: (1) the presence of a dilated aortic root or ascending aorta in the parasternal long-axis view (a high probe position may be needed for proper imaging of the ascending portion); and (2) a dilated arch or abdominal aorta (suprasternal notch and subxiphoid views respectively) ( Fig. 49.4 ). A dissection flap may be seen from any of these views, but the lack of such a flap is not definitive evidence to rule out an aortic dissection. Detection of complications from dissection is more likely, such as acute aortic regurgitation or pericardial effusion. Whenever dissection is suspected, more advanced imaging techniques must be used, such as TEE, chest CT, or MRI. Their accuracy is similarly high, and the method of choice should depend on the availability and expertise at each center.

Aortic dissection. A 43-year-old woman experienced sudden onset of a lacerating chest pain (CP), 10/10 in intensity from onset. A, Parasternal long-axis view on a transthoracic echocardiogram showing a dissection flap in the ascending aorta ( white arrow ) and pericardial effusion ( blue arrow ). B, A subxiphoid view with a long axis of the abdominal aorta shows distal extension of the dissection flap ( arrow ). C, Transesophageal echocardiography provided further details. The arrow shows the dissection flap extending proximally to the sinotubular junction, sparing the aortic root and the coronary ostia. In addition, a site of aortic rupture was identified in the ascending aorta.

TEE is unique in that it can be performed at the bedside when patients are hemodynamically unstable, or in the operating room as the patient is prepared for surgery. In addition, a TEE does not require radiation or contrast agents, which is particularly important because the clinical situation may be complicated by acute renal injury due to shock or renal ischemia. Although all three previously mentioned modalities have similar accuracy in detecting dissection, complications are better diagnosed and characterized by TEE. These include pericardial effusion and its hemodynamic consequences (impending or overt cardiac tamponade), aortic regurgitation and its underlying mechanism (important in determining need for aortic valve replacement), and aortic rupture.

Pericardium

The diagnosis of acute pericarditis should be made on the basis of clinical features such as the quality of the CP (pleuritic, worse in supine position), typical ECG findings (diffuse concave ST elevation without reciprocal ST depression; PR depression) and presence of a pericardial rub in auscultation. However, these features are not always evident. A pericardial effusion in TTE is frequently present ( Fig. 49.5 ), reported in as many as 60% of patients with acute presentation. Although the effusion is usually small, approximately 5% present with cardiac tamponade. Therefore a careful examination of cardiac chamber compression, respiratory flow variation by pulsed wave Doppler at the mitral and tricuspid inflow, and inferior vena cava diameter and collapsibility should be performed regardless of the size of the effusion.

Myopericarditis. Parasternal long-axis view of a transthoracic echocardiogram (TTE) on a 42-year-old woman who experienced chest pain 2 weeks after an upper respiratory viral infection. An ECG revealed ST elevation, laboratory studies showed mild elevation of troponin I level, and cardiac catheterization revealed no blockages in coronary arteries. The TTE showed a small to moderate-sized pericardial effusion ( arrows ) and left ventricular ejection fraction of 30% with moderate global hypokinesis, which subsequently improved to 50% after a 2-week treatment with ibuprofen and colchicine.

Left ventricular thrombosis

Previous studies have demonstrated that 1.5% to 3.6% of acute MIs are complicated by systemic embolism, ^, and left ventricular (LV) mural thrombus is most often the responsible culprit. The risk of developing LV thrombus varies with location and size of the MI. A review of the GISSI-3 database revealed that 5.1% of patients treated with fibrinolytic therapy for an acute MI were diagnosed with an LV thrombus by predischarge transthoracic echocardiography. Patients who sustained an anterior MI were at a higher risk of developing LV thrombosis (11.5% versus 2.3% of patients with MIs at other locations). Similarly, in patients treated with percutaneous coronary intervention and dual antiplatelet therapy for an acute anterior MI, 10% and 15% were diagnosed with an LV thrombus by serial echocardiography at 1 week and 3 months, respectively.

LV thrombosis in the setting of an acute MI is typically seen at the LV apex, which is often akinetic as a result of the infarction. Two-dimensional transthoracic echocardiography is the most frequently used imaging modality for the detection of LV thrombus; the apical view is the best window to visualize an apical thrombus ( Fig./Video 50.1 , A ). The echocardiographic appearance of an apical thrombus is characterized by a nonhomogeneous echodensity with a margin distinct from the underlying akinetic or dyskinetic LV apex. This characteristic appearance may allow differentiation of a true LV thrombus from chordae tendineae or artifacts. A protruding configuration and free mobility of LV thrombi are predictors of systemic embolization.

Apical views of noncontrast ( A ) and contrast ( B ) transthoracic echocardiography. Note the anteroapical regional wall motion abnormalities and the demonstration of a filling defect at the left ventricular apex by contrast echocardiography ( right ), consistent with a left ventricular apical thrombus measuring 1.5 × 2.3 cm.

Contrast echocardiography is particularly helpful in patients with suboptimal acoustic windows and in those with prominent LV apical muscle bands or trabeculations, which can confound the recognition of a thrombus (see Fig./Video 50.1 , B ). Multiple studies have demonstrated contrast echocardiography’s superior sensitivity and accuracy in detecting an LV thrombus when compared with noncontrast echocardiography. ^, For instance, in one study that examined the use of contrast in nondiagnostic transthoracic echocardiograms for the purpose of detecting LV thrombus, 90% of these studies became definitive in establishing whether an LV thrombus was present after the use of contrast. Systemic anticoagulation therapy is recommended in patients who are diagnosed with an LV thrombus after an acute MI to reduce the risk of embolization.

Postinfarction ventricular septal rupture

Rupture of the ventricular septum after an acute MI is rather uncommon, occurring in less than 1% of total infarcts. However, the incidence of postinfarction ventricular septal ruptures (VSRs) is higher (2% to 5%) in patients with cardiogenic shock (3.9% in the SHOCK Trial Registry and randomized SHOCK Trial). The typical clinical presentation is the development of a new holosystolic murmur and a precordial thrill along with abrupt and progressive hemodynamic deterioration. VSRs can occur as a complication of both anterior and nonanterior MIs. Apical VSRs are more commonly associated with an anterior MI, whereas VSRs associated with an inferior MI often occur in the posterobasal region of the ventricular septum. Echocardiographic examination therefore must thoroughly evaluate both of these regions of the ventricular septum ( Fig./Video 50.2 ). Although visualization of the defect may be difficult, a postinfarction VSR should be suspected in the presence of severe wall motional abnormalities of the distal ventricular septum. Color Doppler imaging typically demonstrates a shunt from the LV to the right ventricle (RV). Peak flow velocity across the site of rupture measured by continuous wave Doppler interrogation corresponds to the pressure gradient between the LV and RV, and can therefore be used to estimate RV systolic pressure (RV systolic pressure = systolic blood pressure − pressure gradient between LV and RV; in the absence of LV outflow tract or aortic valve obstruction, the systolic blood pressure would equal the LV systolic pressure). In addition, continuous wave Doppler assessment may reveal a nearly continuous shunt through the VSR except during early diastole. Pulsed wave and continuous wave Doppler interrogations are exceedingly sensitive in the localization of postinfarction VSRs. This diastolic left-to-right shunt is secondary to an elevated LV diastolic pressure in the setting of an acute or recent MI. It is also important to note that the magnitude of the left-to-right shunt and the intensity of the systolic murmur are inversely proportional to the size of the infarct and directly related to residual LV systolic function.

Transthoracic echocardiogram demonstrates the etiology of a loud systolic murmur post–myocardial infarction: a ventricular septal rupture with left-to-right shunting.

Left ventricular free wall rupture

LV free wall rupture is the second leading cause of mortality, following cardiogenic shock, in patients with an acute MI. The incidence of free wall rupture is estimated to be 6% (2.7% of patients in the SHOCK Trial Registry), but it accounts for 15% of in-hospital mortality after an acute MI. ^, LV free wall rupture most frequently presents as a catastrophic event—electromechanical dissociation (EMD) due to cardiac tamponade. However, in some patients, rupture of the ventricular free wall takes a more stuttering course. In such patients, prompt diagnosis and surgical intervention are necessary. Echocardiography is the diagnostic modality of choice whenever there is any suspicion of free wall rupture. Any pericardial effusion in a patient with sudden hemodynamic compromise after an acute MI should suggest the diagnosis. Enlarging pericardial effusions with echodense structures (thrombus) are characteristic and, when seen in patients with hemodynamic compromise, are greater than 98% specific for LV free wall rupture. Echocardiography is also used to locate the point of rupture, which is typically at the junction of normal and infarcted myocardium.

LV apical aneurysms may develop secondary to myocardial scar formation and thinning of the myocardium with subsequent expansion of the LV ( Fig./Video 50.3 , A ). In some patients, however, either the rupture occurs over time or the perforation is incomplete, resulting in the development of an LV pseudoaneurysm. Pseudoaneurysms remain somewhat contained within a limited segment of the pericardium and are commonly in the inferolateral or inferoposterior walls. As with other mechanical complications of an acute MI, LV pseudoaneurysms can also be identified by echocardiography and are typified by a pseudoaneurysm cavity that communicates with the LV chamber via a very narrow neck (diameter of entry site less than <SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='1/2′>1/21/2
1 / 2
of maximal diameter of the pseudoaneurysm), and frequently contains thrombus (see Fig./Video 50.3 , B ). The characteristic to-and-fro blood flow through the site of rupture can be detected with Doppler and color flow imaging.

Echocardiography is useful at differentiating left ventricular (LV) aneurysm (wide entry neck) ( A ) from LV pseudoaneurysm (narrow entry neck) ( B ).

Acute mitral regurgitation and papillary muscle rupture

Mitral regurgitation is common among patients with an acute MI. Its prevalence is up to 50%, and the presence of mitral regurgitation portends a worse short-term and long-term prognosis. ^, Acute mitral regurgitation in the context of an acute MI can occur as a consequence of several pathophysiologic mechanisms: (1) dilatation of the mitral annulus secondary to left ventricular dilatation, (2) papillary muscle displacement or dysfunction due to the proximity of the insertion of the papillary muscle to the infarcted myocardium, and (3) papillary muscle or chordal rupture.

Although most cases of mitral regurgitation are transient and asymptomatic, papillary muscle rupture is a rare but life-threatening mechanical complication of an acute MI. Previous studies have reported that papillary muscle rupture complicates approximately 1% to 3% of acute MIs with a mortality of 80% when treated with medical therapy alone. The classic presentation of papillary muscle rupture is acute pulmonary edema and cardiogenic shock 3 to 5 days after an acute MI. Physical examination may reveal a new holosystolic murmur, but it is important to note that the intensity of the systolic murmur does not necessarily correlate with the severity of mitral regurgitation. For instance, patients with severe acute mitral regurgitation have rapid equalization of pressures in the left ventricle and left atrium, thus reducing the duration and intensity of the systolic murmur.

A high index of suspicion is required for identifying patients with significant mitral regurgitation associated with an acute MI, and echocardiography plays an essential role in differentiating the underlying mechanism for the mitral regurgitation and in ruling out other etiologies for a new systolic murmur in this clinical setting. Common two-dimensional echocardiographic features of papillary muscle rupture include a flail mitral leaflet with severed chordae or papillary muscle head moving freely within the left heart ( Fig./Video 50.4 ). Complete transection of the papillary muscle is relatively rare, whereas rupture of the tip is more common. Because of differences in coronary blood supply, rupture of the posteromedial papillary muscle (supplied by a single coronary artery) occurs 6 to 10 times more often than rupture of the anterolateral papillary muscle (has dual coronary supply). LV function is often hyperdynamic because of a sudden decrease in afterload, and regional wall motion abnormalities may be subtle or unrecognized. Color Doppler assessment typically demonstrates eccentric mitral regurgitation, which may lead to underestimation of the degree of mitral regurgitation. Patients with papillary muscle rupture usually present with significant distress and hemodynamic compromise, resulting in suboptimal transthoracic imaging windows. Transesophageal echocardiography may therefore be required to establish the diagnosis and to determine the severity of mitral regurgitation. Afterload reduction and emergent surgical intervention are the mainstays of management for these patients.

Transesophageal echocardiography demonstrates a flail posterior mitral leaflet ( A ) with the tip of a torn papillary muscle attached to it ( B ). Color Doppler assessment reveals severe anteriorly directed mitral regurgitation ( C ).

Left ventricular outflow tract obstruction

Dynamic left ventricular outflow tract (LVOT) obstruction has traditionally been described as a hallmark of hypertrophic obstructive cardiomyopathy, and it occurs as a result of asymmetric ventricular septal hypertrophy and systolic anterior motion of the mitral valve. In recent years, dynamic LVOT obstruction that complicates an acute anterior MI has been increasingly recognized. The common underlying mechanism for the development of acute LVOT obstruction is the compensatory hyperdynamic contraction of the basal inferolateral and inferior segments in the setting of an anteroapical MI and LV apical akinesis. Hyperkinesis of the basal segments leads to a reduction in the LVOT cross-sectional area, acceleration of blood flow across the LVOT, systolic anterior motion of the mitral valve, and consequently LVOT obstruction. These patients typically present with an acute anterior MI, whereas unstable hemodynamics and a new systolic murmur are found on physical examination. Significant posteriorly directed mitral valve regurgitation secondary to systolic anterior motion of the mitral valve may also lead to acute pulmonary edema. The incidence of dynamic LVOT obstruction after an acute MI is unknown, but it is believed to be more common among women and elderly patients with a small LVOT area or basal septal hypertrophy due to chronic hypertension. ^, LVOT obstruction has also been reported in up to one third of patients with takotsubo cardiomyopathy, or apical ballooning syndrome.

Urgent echocardiography should be performed in patients with a new systolic murmur and unstable hemodynamics in the setting of an acute MI. Transthoracic echocardiography should be considered the diagnostic modality of choice to assess dynamic LVOT obstruction, whereas transesophageal echocardiography can be used in patients with suboptimal acoustic windows. Common two-dimensional echocardiographic features include regional wall motion abnormalities of the anteroapical segments, hyperkinesis of the basal ventricular segments, and systolic anterior motion of the mitral valve ( Fig./Video 50.5 ). In the presence of dynamic LVOT obstruction, color Doppler imaging will demonstrate turbulent blood flow across the LVOT, and posteriorly directed mitral valve regurgitation may also be present. Continuous wave Doppler examination of the LVOT from the apical imaging window will reveal a late-peaking systolic (dagger-shaped) Doppler signal with a peak velocity that correlates with the degree of LVOT obstruction. Other differential diagnoses for a new murmur and hemodynamic compromise after a recent MI, such as VSR and papillary muscle rupture, can also be ruled out with echocardiography. Echocardiography plays a critical role in differentiating the previously mentioned underlying mechanisms, and a correct echocardiographic diagnosis has important implications for the management of these patients. For instance, the most appropriate treatment strategy for a patient with LVOT obstruction includes the infusion of intravenous fluids, discontinuation of vasodilators or inotropic agents, and the administration of beta-blockers, alpha-adrenergic agonists, or both. In contrast, urgent surgical repair is recommended for patients with postinfarction VSR or papillary muscle rupture.

Apical long-axis view of transthoracic echocardiography demonstrates akinesis of the left ventricular apex and systolic anterior motion of mitral valve ( A ). Color Doppler assessment of the left ventricular outflow tract (LVOT) reveals turbulent flow across the LVOT and significant posteriorly directed mitral regurgitation ( B ). Late-peaking continuous wave Doppler signal is consistent with dynamic LVOT obstruction ( C ).

Right ventricular infarction

Up to half of acute inferior MIs are complicated by RV infarction, but significant hemodynamic compromise is relatively infrequent and long-term prognosis is generally favorable. Data from the SHOCK Trial Registry, however, suggest that patients who develop cardiogenic shock as a result of RV infarction have similar risk of mortality when compared with those who develop cardiogenic shock due to LV infarctions.

Echocardiography is useful in the evaluation of patients with presenting symptoms of acute inferior MI and hemodynamic compromise. Echocardiographic features associated with RV infarction have been identified in a few small studies, and these include dilatation of the RV cavity, variable degrees of wall motion abnormalities of the right ventricular free wall, systolic paradoxical ventricular septal motion, plethora of the inferior vena cava, reduced right ventricular ejection fraction, and impaired tricuspid annular plane systolic excursion (TAPSE). ^, Other studies have also demonstrated that the tissue Doppler systolic velocity (S′) of the lateral tricuspid annulus is not only a sensitive and specific marker of RV involvement in an inferior MI, but also an independent predictor of cardiovascular outcomes. ^, It is important to note that the specificity of the previously mentioned findings may be reduced in patients with other medical conditions that can result in RV enlargement and dysfunction, such as pulmonary hypertension and pulmonary embolism.

In patients who develop hypoxemia after sustaining an inferior MI, RV infarction and a clinically significant right-to-left shunt through a patent foramen ovale should be considered ( Fig./Video 50.6 ). This occurs as a result of impaired RV compliance and elevated right atrial pressure in the setting of an RV infarction. Transthoracic echocardiography with color Doppler imaging or the injection of agitated saline (visualization of contrast medium in the left atrium after opacification of the right atrium) may help establish RV infarction. Alternatively, transesophageal echocardiography may be the imaging test of choice in patients with suboptimal imaging windows.

Transesophageal echocardiography demonstrates significant enlargement and systolic dysfunction of the right ventricle ( A ). Deviation of the interatrial septum toward the left side during the entire cardiac cycle suggests much elevated right atrial pressure. Color Doppler assessment of the interatrial septum reveals a right-to-left shunt through the patent foramen ovale ( B ).

Diagnosis

Echocardiography can show a focal wall motion abnormality that may indicate the presence of coronary artery disease (CAD). Examples of an apical and inferior wall motion abnormalities can be seen in Video 51.1 and Video 51.2. Even in patients without established CAD, a wall motion abnormality is associated with a 2.4- to 3.4-fold increase in risk of cardiac events. Wall motion analysis should be done using the method proposed by the American Society of Echocardiography (ASE) in 1989, with particular attention to endocardial thickening. If endocardial definition is poor, an intravenous contrast agent should be used. The addition of contrast has been shown to improve accuracy and interobserver variability in the assessment of regional wall motion. The 17-segment model proposed by the ASE should be used to describe the location of wall motion abnormalities (see Chapter 30, Fig. 30.1 ).

Echocardiography can also accurately measure left ventricular ejection fraction, which is a very important prognostic marker in patients with CAD. The ability to determine the LV ejection fraction accurately also requires endocardial definition. If endocardial definition is suboptimal, the addition of contrast has been demonstrated to improve interobserver variability as well as accuracy.

Stress echocardiography

Stress echocardiography is a very important modality in the diagnosis and prognosis of CAD. It has advantages over other modalities because it does not require a radiation source, and it is less expensive and has shorter imaging time compared with nuclear techniques. Furthermore, other important information may be obtained from the resting images about right ventricular size and function, the aortic root, and pericardial and valvular structures. In a study of approximately 1223 patients who had a stress echocardiogram, 5% were found to have moderate mitral regurgitation by a focused Doppler exam before the stress echocardiogram. This may be important adjunctive clinical information that was unrecognized before the stress echocardiogram.

Stress echocardiography relies on the principle that a wall motion abnormality will occur in the setting of a coronary lesion that limits flow when myocardial oxygen demand is increased. Stress echocardiography is more accurate than stress electrocardiogram (ECG) in the detection of CAD because wall motion abnormalities occur earlier in the ischemic cascade. A meta-analysis of exercise echocardiography and nuclear stress testing showed similar sensitivities (85% for echocardiography, 87% for nuclear stress testing) and a higher specificity for stress echocardiography (77% versus 64%) for the detection of CAD. The sensitivity for the detection of CAD is higher in patients with multivessel disease than in patients with single-vessel disease. Sensitivity is worst in the circumflex distribution because it supplies a smaller area of myocardium. Treadmill exercise echocardiography produces a higher workload than bicycle echocardiography. Supine bicycle echocardiography offers the ability to image the heart throughout the exercise protocol, not just at peak exercise. In our lab, we use treadmill echocardiography for the diagnosis of CAD and bicycle echocardiography in the evaluation of valvular heart disease. It is especially important to obtain the postexercise images within 60 seconds because ischemic wall motion abnormalities may be transient. The apical images should be obtained first because the entire ventricle from base to apex is imaged in the apical two-chamber and apical four-chamber views. Use of contrast agents can be very helpful and can convert a nondiagnostic examination to a diagnostic examination, as shown in Video 51.3. In patients who cannot exercise, dobutamine stress echocardiography (DSE) is performed. Dobutamine is infused in staged increments of 10 μg/kg/min until the target heart rate is achieved, symptoms develop, or end-study indications (significant arrhythmias, hypotension, or patient intolerance) occur. If there are no contraindications to atropine and target heart rate is not achieved after 3 minutes of dobutamine at 40 μg/kg/min, 0.5 mg atropine may be given intravenously and repeated once if needed to achieve target heart rate.

Image interpretation

Wall motion in each left ventricular segment is scored on resting and stress images according to the following system: 1 = normal; 2 = hypokinetic; 3 = akinetic; and 4 = dyskinetic ( Fig. 51.1 ). Using this system, a wall motion score index can be derived at peak stress. A normal wall motion score index is 1.0. An elevated exercise wall motion score index was associated with increased rates of death or nonfatal myocardial infarction in a study of 5798 patients who underwent exercise echocardiography for suspected or known CAD ( Fig. 51.2 ). This finding was also reproduced in 860 patients who had dobutamine stress echocardiography. In the setting of left main coronary artery disease, left ventricular dilatation is much more commonly demonstrated by exercise echocardiography (80%) compared with DSE (12%). The right ventricle should also be monitored because abnormal right ventricular wall motion at stress has prognostic value independent of left ventricular ischemia.

Wall motion scoring diagram.

The wall motion score equals the score of all segments divided by the number of segments analyzed. A normal score is 1.0.

Relationship between the wall motion score index and cardiac event rate.

(Adapted with permission from Arruda-Olson AM, Juracan EM, Mahoney DW, et al.: Prognostic value of exercise echocardiography in 5,798 patients: is there a gender difference? J Am Coll Cardiol 39:625-631, 2002.)

Prognostic value of stress echocardiography

Exercise stress echocardiography has been shown to be a very helpful prognostic indicator of cardiac events. In patients without known CAD, normal exercise echocardiography confers an excellent prognosis, with a cardiac event rate of 0.9% per year. In patients with known or suspected CAD and good exercise capacity, the percentage of the left ventricle that had severely abnormal wall motion after exercise was a prognostic marker for cardiac events.

Mechanisms of reversibility

Experimental evidence has revealed that repeated episodes of ischemia in the setting of CAD contribute to development of chronic systolic dysfunction or hibernation. It would logically follow that correction of ischemia could result in better outcomes. In hibernating myocardium that has recovered function, coronary flow reserve is restored. In an observational study from 30 years ago, surgical revascularization improved systolic function and functional status in patients with severely depressed systolic function. But the risk of revascularization is higher in patients with depressed systolic function, and it is important to determine if there is viability before performing a high-risk revascularization procedure.

Role of dobutamine stress echocardiography in viability assessment

DSE has been shown to be a very helpful modality in the assessment of myocardial viability. Both low- and high-dose infusions of dobutamine are used to generate a biphasic response in hibernating myocardium. The wall motion in an abnormally contracting segment will improve at low dose and then worsen after a high dose. This response has been shown to be most predictive of recovery after revasculariztion. If a wall is thinned (and often bright) on echocardiographic imaging at rest, with an end-diastolic wall thickness of less than 6 mm, viability is very unlikely.

Importance of viability

The detection of viability by DSE has proven to be clinically important in making decisions regarding coronary revascularization. In a study of 318 patients, all with CAD and an ejection fraction of less than 35%, revascularization improved survival compared to medical therapy in the patients with viability demonstrated by DSE. The number of viable segments on DSE is also important. The number of viable segments is positively correlated with improvement in left ventricular ejection fraction following revascularization, as shown in Fig. 51.3 .

Relationship of the number of viable segments determined by dobutamine stress echocardiography to the improvement of ejection fraction and the reduction of cardiac events post-revascularization.

(Adapted from Meluzin J, Cerny J, Frelich M, et al. Prognostic value of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction. Investigators of this multicenter study, J Am Coll Cardiol 32:912-920, 1998.)

Conclusion

Echocardiography plays a pivotal role in the management of stable CAD. It is the most widely used technique to assess left ventricular wall motion and systolic function. Stress echocardiography is an effective tool to diagnose CAD because it has comparable accuracy to nuclear modalities and it minimizes cost and does not require radiation exposure. DSE can identify the presence and extent of viable myocardium in patients with CAD and depressed left ventricular systolic function, which is critically important information for making decisions about coronary revascularization in patients with these complex conditions.