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Echocardiography in pulmonary vascular disease
Cardiol Clin 22 (2004) 383–399
Echocardiography in pulmonary vascular disease Lori B. Daniels, MDa,b, David E. Krummen, MDa,b, Daniel G. Blanchard, MD, FACCa,b,* a
Division of Cardiology, Department of Medicine, University of California, San Diego School of Medicine, University of California, San Diego, 200 West Arbor Drive, San Diego, CA 92103, USA b University of California, San Diego Medical Center, 200 West Arbor Drive San Diego, CA 92103, USA
The assessment of pulmonary artery pressure, right ventricular function, right ventricular filling pressure, and tricuspid regurgitation provides invaluable information in the care of patients with pulmonary vascular disease. Echocardiography provides a rapid, noninvasive, portable, and accurate method to evaluate these parameters and also provides information on left ventricular and valvular function. Echocardiography has therefore become one of the most commonly performed diagnostic studies in patients with pulmonary vascular disease, and the technique’s applications in this area are likely to grow. This article presents an overview of the current uses of echocardiography in pulmonary vascular disease and pulmonary hypertension.
Echocardiographic measurements in pulmonary hypertension Measurement of right ventricular volume and function Measurement of right ventricular volume and function is important in making the diagnosis of pulmonary hypertension, but, because of the complex three-dimensional shape of the right ventricle, accurate measurement of right ventricular size and ejection fraction is difficult. In the apical four-chamber view, enlargement of the right ventricle can be determined qualitatively * Corresponding author. UCSD Medical Center, 200 W. Arbor Drive, #8411, San Diego, CA 92103. E-mail address: [email protected] (D.G. Blanchard).
when its chamber cross-sectional area exceeds that of the left ventricle (Fig. 1). In addition, right ventricular enlargement is present when the distal portion of the right ventricle shares space with the left ventricle at the cardiac apex in the apical four-chamber view. Normally, the cardiac apex is exclusively composed of left ventricular myocardium. Quantitative measurements of right ventricle size, thickness, and cross-sectional area can also be obtained [1]. Right ventricular systolic function can be expressed as the percent of change in right ventricular area during the cardiac cycle: ð½EDA ESA EDAÞ 100% EDA is the right ventricular area from the apical four-chamber view at end-diastole, and ESA is the right ventricular area at end-systole. Normal right ventricular fractional area change is 40% to 45% [2]. Because right ventricular functional measurement is highly dependent upon afterload and transseptal pressure gradients, the percent of change in cross-sectional area is not routinely quantified [3]. Tricuspid regurgitation Tricuspid regurgitation is often present in the setting of pulmonary hypertension and ranges from mild to severe. Tricuspid regurgitation may be caused by dilatation of the tricuspid annulus and morphologic alteration of right ventricular geometry [4] as well as by chordal traction of the valve leaflets [5]. Although the severity of tricuspid regurgitation does not necessarily correlate with the degree of pulmonary hypertension, reversal of pulmonary hypertension leads to
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artery systolic pressure is first to record the maximum tricuspid regurgitant jet velocity (VTR). This velocity can then be translated into the pressure gradient between the right ventricle and right atrium using the modified Bernoulli equation. The accuracy of this method depends on obtaining the true maximum VTR. The interrogating Doppler ultrasound beam must be parallel (or nearly so) to the direction of blood flow in the jet of TR (Fig. 2). The apical or right ventricular inflow views are most commonly used for this analysis. The peak right ventricular and pulmonary artery systolic pressure can then be calculated (in the absence of pulmonic stenosis) as Fig. 1. Apical four-chamber view in severe pulmonary hypertension. The right atrium (RA) and ventricle are markedly enlarged, and the right ventricle (RV) is hypertrophied. The interventricular septum is shifted leftward, and the left-heart chambers appear compressed.
significantly decreased tricuspid regurgitation in many cases, especially when the tricuspid regurgitation is caused by annular dilatation [6]. Estimation of pulmonary arterial pressure by the Bernoulli equation Transthoracic echocardiography (TTE) provides a readily available, noninvasive assessment of right-sided intracardiac pressures. The most reliable approach for approximating pulmonary
Pulmonary artery pressure ¼ 4VTR2 þ right atrial pressure ½7: Right atrial pressure can be estimated from the size and variation in the inferior vena cava (IVC) during quiet respiration. Best visualized from a subcostal window, the IVC normally has a diameter of 1.2 to 2.3 cm (Fig. 3) and should collapse by at least 50% during inspiration [8]. IVC dilation (or lack of collapse during inspiration) correlates with a higher right atrial pressure (eg, 10–15 mm Hg) [7]. In the setting of a dilated IVC, a complete lack of variation in IVC diameter with quick inspiration (a sniff) suggests a right atrial pressure of at least 20 mm Hg. Pulmonary artery diastolic pressure also can be estimated from the velocities of the pulmonic
Fig. 2. Continuous-wave spectral Doppler tracing of tricuspid regurgitation (TR) recorded in a modified apical fourchamber plane. The peak velocity of the TR jet is 5.2 m/s, suggesting a gradient of 108 mm Hg.
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nary hypertension include a decrease in the velocity-time integral of flow through the pulmonic valve and a shortening of the acceleration time (measured from beginning of flow through the pulmonic valve to peak velocity.) The acceleration time (AT, in milliseconds) can be used to estimate the mean pulmonary artery pressure in mm Hg [11,12] according to the equation Mean pulmonary artery pressure ¼ 80 ðAT=2Þ:
Acute pulmonary embolus Fig. 3. Subcostal view of the inferior vena cava (IVC) emptying into the right atrium (RA). A hepatic vein is also visible (arrow).
regurgitant Doppler tracing [9,10] (Fig. 4). Again, using the modified Bernoulli equation, the enddiastolic velocity of the pulmonic regurgitation jet can be used to calculate the instantaneous gradient between the pulmonary artery and the right ventricle. The pulmonary artery diastolic pressure is obtained by adding this calculated gradient to the estimated right atrial pressure. Other findings in right ventricular dysfunction and pulmonary hypertension Other characteristic Doppler abnormalities seen in right ventricular dysfunction and pulmo-
Typical findings on transthoracic echocardiography Depending on the size of the thromboembolus, patients with acute pulmonary embolism may have a number of abnormalities on TTE. Rarely, a large thrombus may be directly visualized in a proximal pulmonary artery or in transit in the right-heart chambers (Fig. 5A–C) [13]. The most common echocardiographic findings, however, are caused by acute right-sided pressure overload. With acute massive pulmonary embolism, the right ventricle dilates and becomes markedly hypokinetic. Abnormal motion of the interventricular septum with flattening or bulging toward the left ventricle in diastole may be seen (Fig. 6). Such paradoxical septal motion can result in left ventricular diastolic impairment, with decreased early diastolic filling
Fig. 4. Spectral Continuous-Wave Doppler tracing of pulmonic insufficiency (measured in the parasternal short-axis view at the base of the heart). The end-diastolic velocity is 2.2 m/s, suggesting a gradient between the pulmonary artery and right ventricle of 19 mm Hg at end-diastole.
Fig. 5. (A) Parasternal short-axis transthoracic echo image of a large thrombus (T) lodged in the bifurcation of the right and left main pulmonary arteries. Ao, ascending aorta; PA, main pulmonary artery. (B) Subcostal four-chamber view of a serpentine right atrial thrombus (**). On real-time imaging, the thrombus was very mobile. LV, left ventricle; RV, right ventricle. (C) Transesophageal image of a thrombus in transit. A venous thromboembolus has traveled to the right atrium (RA) and is lodged in a patent foramen ovale. A portion of the thrombus extends into the left atrium (LA).
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and increased reliance on the atrial kick (this process has been called the reverse Bernheim phenomenon) [14,15]. On Doppler examination of transmitral diastolic blood flow, this phenomenon is seen as a decrease in the early rapid filling velocity (E wave) and an increase in the atrial contraction velocity (A wave). This septal impairment of left ventricular diastolic filling may further contribute to the low cardiac output seen in cases of massive pulmonary embolism. A ratio of right ventricle–to–left ventricle enddiastolic diameter (measured in the parasternal or subcostal view) greater than the upper normal limit of 0.6 helps indicate right ventricular dysfunction and may distinguish between massive and nonmassive pulmonary embolism [16,17]. In addition, tricuspid regurgitation is common in acute pulmonary embolism (Fig. 7) and provides a useful way to assess pulmonary artery pressure. The right atrium and the IVC often dilate in acute massive pulmonary embolism, reflecting elevated right-sided pressures, and the IVC fails to collapse normally during inspiration. Interatrial shunting can occur if a patent foramen ovale is present and right ventricular pressure is significantly elevated. Unfortunately, the Doppler and two-dimensional echocardiographic findings of right ventricular dysfunction and right-sided pressure overload are not specific for pulmonary embolism: other diseases, including primary pulmonary hypertension, right ventricular myocardial infarction, cardiomyopathy, or right ventricular dysplasia, or acute exacerbations of obstructive pulmonary dis-
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ease may produce similar findings. Hypokinesis of the right ventricle free wall with sparing of apical function (McConnell’s sign) has been proposed as a relatively specific sign of right ventricular dysfunction caused by acute pulmonary embolism rather than other causes, but the overall clinical utility of this observation is debatable [18]. The degree of pulmonary hypertension seen with acute pulmonary embolism is usually mild to moderate, but right ventricular dysfunction is not universally present in acute pulmonary embolism [19]. Approximately 20% of patients with acute pulmonary embolism confirmed by ventilationperfusion (V/Q) scan or angiography may have normal findings on TTE [20,21]. Visualization of the right and left pulmonary arteries is sometimes difficult, and detection of pulmonary thromboemboli is unusual in most cases of pulmonary embolism. Furthermore, echocardiographic images may be of limited usefulness in patients who are obese, have hyperinflated lungs, or are immobile (including those on mechanical ventilators). Because of these limitations, TTE is not recommended as a primary diagnostic tool in acute pulmonary embolism. Nonetheless, it may be helpful in diagnosing or excluding alternative causes of sudden hemodynamic instability, including cardiac tamponade, aortic dissection, and acute valvular insufficiency [22]. Typical findings on transesophageal echocardiography Transesophageal echocardiography (TEE) can detect all the findings detected by TTE but is much more effective in the direct visualization of thrombi in the central pulmonary arteries. TEE visualizes the main pulmonary artery and the right pulmonary artery well, although the intervening left main bronchus may obscure the left pulmonary artery In the appropriate clinical setting, the finding of an intraluminal pulmonary artery mass is reasonably specific for the diagnosis of acute pulmonary embolism [7–9,23,24]. The sensitivity of TEE in acute pulmonary embolism varies among studies and depends on operator expertise and patient selection. False-positive results, however, are distinctly unusual [7–9,24]. Uses of echocardiography in acute pulmonary embolism
Fig. 6. Short-axis view in right ventricular overload. The interventricular septum is flattened and pushed toward the left ventricle. LV, left ventricle; RV, right ventricle.
Although TTE is not the recommended diagnostic test for pulmonary embolism, it nonetheless can play a major role in the assessment of
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Fig. 7. Short-axis view through the base of the heart showing significant tricuspid regurgitation. A multicolored jet of tricuspid regurgitation is seen in the right atrium (RA) during systole. LV, left ventricle; RV, right ventricle.
prognosis and management of this condition. Echocardiographic analysis of right ventricular function has proven useful in the risk stratification of patients with pulmonary embolism. In a recent study of 209 consecutive patients with pulmonary embolism, the 65 who were hemodynamically stable but had right ventricular dysfunction on TTE had an in-hospital mortality rate of 5% versus 0% in those without right ventricular dysfunction [25]. In another study of 126 consecutive pulmonary embolism patients, echocardiography emerged as the strongest predictor of in-hospital mortality, because the risk of in-hospital death was six times greater for the patients with right ventricular dysfunction than for those with normal right ventricular function [21]. At 1-year follow-up, there was still a 2.4 relative risk of mortality associated with right ventricular dysfunction. In patients without an underlying malignancy, the pulmonary embolism mortality rate was 7.7% in patients with right ventricular hypokinesis but 0% in those without right ventricular dysfunction. Right ventricular hypokinesis on baseline echocardiography was also an important predictor of increased mortality in the International Cooperative Pulmonary Embolism Registry. Right ventricular hypokinesis was associated with a twofold increase in mortality and was as important a predictor of poor outcome as advanced age, cancer, congestive heart failure, and renal insufficiency [26]. Finally, in the Manage-
ment, Strategy and Prognosis of Pulmonary Embolism Registry (MAPPET) study of 1001 patients, right ventricular dysfunction was an independent and significant marker of increased mortality [27]. Whether right ventricular dysfunction should be used to determine which patients receive thrombolytic therapy remains controversial. There is a general consensus that thrombolysis is the treatment of choice in patients with massive pulmonary embolism accompanied by hemodynamic collapse, and in these patients echocardiography is useful for monitoring changes in cardiac function with treatment [28]. There is, however, a significant subset of patients with acute pulmonary embolism (as high as 40%) who do not have significant hemodynamic compromise but still exhibit right ventricular dysfunction on TTE [25,26]. These patients may benefit from thrombolytic therapy. In a randomized trial of thrombolysis plus anticoagulation versus anticoagulation alone, Goldhaber et al [28] found that 5 of 23 patients with right ventricular hypokinesis and dilatation had recurrent pulmonary embolism after receiving intravenous heparin alone, whereas pulmonary embolism did not recur in any of the 23 patients with right ventricular dysfunction who received thrombolytics. Patients given thrombolytics also had greater recovery of right ventricular function at 24 hours, improved absolute pulmonary perfusion, and decreased right ventricular end-diastolic
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area, though overall mortality was unchanged [28]. In the MAPPET registry, Konstantinides et al [27,29] found a lower 30-day mortality in subgroup of 719 normotensive patients with pulmonary embolism and right ventricular overload who were treated with thrombolytics than in those treated with intravenous heparin alone (4.7% mortality in the 169 patients initially treated with thrombolytics versus 11.1% in the 550 patients who initially received anticoagulation alone, P = 0.016). Other studies, however, have had conflicting results. A recent study by Hamel et al [30] assessed 128 patients with massive pulmonary embolism, stable hemodynamics, and right ventricular dysfunction. In their analysis, treatment with low-molecular-weight heparin resulted in a trend toward decreased mortality compared with treatment with thrombolytics (0% versus 6.3%, P = 0.12), with fewer major bleeding events. Overall, it seems that patients with acute pulmonary embolism and right ventricular dysfunction detected on echocardiography represent a group at higher risk [31]. These patients merit aggressive therapy, but it is not completely clear whether the addition of thrombolytics decreases the risk of early death. Another subgroup of patients who may benefit from echocardiography is those presenting with acute pulmonary embolism and significant pulmonary hypertension (pulmonary artery systolic pressure >50 mm Hg). In a 5-year study of 78 patients with pulmonary embolism, Ribeiro et al [32] found that this degree of initial pulmonary hypertension conferred an odds ratio of 3.3 for persistent pulmonary hypertension or right ventricular dysfunction. They reported an early exponential rate of decline in pulmonary artery pressures, followed by a stable period after 6 weeks. In this study, 5% of patients with acute pulmonary embolism developed persistent cardiopulmonary disability and chronic right-heart dysfunction, a percentage higher than previously estimated [33–35]. Thus, follow-up echocardiography at 6 weeks can identify the high-risk subgroup of patients with persistent pulmonary hypertension and right ventricular dysfunction who are potential candidates for pulmonary thromboendarterectomy [36]. Recommendations for transthoracic echocardiography in acute pulmonary embolism As discussed previously, many patients with acute pulmonary embolism have normal echocar-
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diograms, and the routine use of TTE for diagnosis of pulmonary embolism is not recommended. Echocardiography may be appropriate, however, when the diagnosis is in question. In such cases, pulmonary embolism may be confirmed or another cause of the patient’s symptoms may be detected. Additionally, TTE is indicated in patients with confirmed pulmonary embolism, because the finding of right atrial or right ventricular thrombi often mandates the use of thrombolytics to prevent recurrent and potentially fatal pulmonary embolism. In hemodynamically unstable patients with suspected pulmonary embolism, TTE can be used as a rapid initial test. If significant right ventricular dysfunction is present, pulmonary embolism is likely. Finally, echocardiography can help monitor treatment response in patients with documented acute pulmonary embolism. Serial echocardiography can predict the development of CTEPH and canassesssuitabilityforfuturepulmonarythromboendarterectomy. Use of transesophageal echocardiography Only a few studies have examined the role of TEE in acute pulmonary embolism. In patients with suspected acute pulmonary embolism who present with shock or recent cardiopulmonary resuscitation, completion of standard diagnostic tests such as V/Q scanning, CT, and pulmonary angiography can be difficult. In these critically ill patients, bedside TEE may be useful. For example, a study of TEE in 25 patients presenting with pulseless electrical activity found that 14 had isolated right ventricular enlargement. Of these, 9 had acute pulmonary emboli [37]. One recent report by Krivec et al [38] examined 24 critically ill patients with unexplained shock and jugular venous distention. They found that 17 patients (70%) had right ventricular dilatation with global hypokinesis. TEE examination detected proximal pulmonary emboli in 12 of these patients and reduced right pulmonary artery flow in one additional patient. Of these 13 patients, 12 eventually had documentation of massive pulmonary embolism (either by V/Q scan or post mortem study). The few studies available suggest that TEE can provide direct visualization of proximal pulmonary arterial thrombi and so can be useful for determining surgical accessibility in patients with massive pulmonary embolism and refractory circulatory collapse.
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Echocardiography in chronic right ventricular overload and pulmonary hypertension The nonspecific nature of symptoms from chronic pulmonary hypertension often impedes the early diagnosis of the condition. For example, Rubin et al [39] reported a mean time from presentation to diagnosis of approximately 2 years in patients with pulmonary hypertension. In general, pulmonary vascular disease should be suspected when symptoms of dyspnea cannot be easily explained. When pulmonary hypertension is suspected from physical examination or screening tests (such as electrocardiography or chest radiographs), Doppler echocardiography is the best subsequent test to evaluate right-heart function and pressure. In many cases, TTE is the first test to detect an elevation of right ventricular pressure [40]. TTE also provides important information about prognosis and response to treatment in these patients [3,41]. Echocardiographic features of chronic pulmonary hypertension Tricuspid valve As noted previously, tricuspid regurgitation is common in the setting of pulmonary hypertension but may regress with reversal of the pressure overload. A recent study by Sadeghi et al [42] evaluated patients with CTEPH and severe tricuspid regurgitation who subsequently underwent pulmonary thromboendarterectomy. Seventy per-
cent of the patients had resolution of tricuspid regurgitation after pulmonary thromboendarterectomy, often despite persistent tricuspid annular dilation. The 30% of patients with persistent severe tricuspid regurgitation had less postoperative decrease in pulmonary artery pressure. Thistlethwaite et al [43] reported that intraoperative classification of pulmonary thromboembolic disease helps predict successful decreases in pulmonary artery pressure and tricuspid regurgitation severity in patients with CTEPH: those with thrombus in the main lobar pulmonary arteries had the greatest improvement in these parameters following pulmonary thromboendarterectomy. Inferior vena cava and right-heart chambers As described previously, the right atrium and IVC are commonly dilated in patients with pulmonary hypertension (Fig. 8). This dilation is generally a manifestation of significant tricuspid regurgitation, elevated right ventricular diastolic pressure, or both. Additionally, elevation of right atrial pressure may cause the interatrial septum to bulge toward the left atrium. Right atrial pressure in chronic pulmonary hypertension can be estimated by means similar to the method described for acute pulmonary embolism. The pulmonary artery is often dilated in the setting of chronic pulmonary hypertension and right ventricular hypertrophy. Pulmonic valvular regurgitation frequently occurs as well, and, as noted previously, the regurgitant flow velocity can
Fig. 8. Subcostal view demonstrating a dilated inferior vena cava (IVC). Diameter of the IVC is more than 2.5 cm. LA, left atrium; RA, right atrium.
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be used to estimate the pulmonary artery diastolic pressure [9,10]. M-mode examination of the pulmonic valve in pulmonary hypertension may show a characteristic W-shaped motion of the valve leaflet during systole [44–46]. This midsystolic closure of the valve and partial reopening in late systole, sometimes called the flying-W sign (Fig. 9), is probably caused by elevated pulmonary vascular resistance and early reflection of the systolic pressure wave within the proximal pulmonary arteries [47]. There also may be a loss of the normal presystolic opening of the pulmonic valve with atrial contraction (the ‘‘a’’ dip). Because of the large difference between right ventricular pressure and pulmonary artery pressure throughout diastole, the pressure generated by the atrial kick is insufficient to open the pulmonic valve even partially. Chronic pulmonary hypertension ultimately leads to right ventricular hypertrophy, enlargement, and depressed systolic function. Echocardiographic measurements of right ventricle wall thickness can be performed from the parasternal and subcostal views, and a value of more than 5 mm is diagnostic for right ventricular hypertrophy [48]. In the setting of right ventricular hypertrophy, the moderator band is often hypertrophied and thickened as well [3]. Left-heart chambers and interventricular septum The left ventricle size is normal to small in severe pulmonary hypertension and right ventric-
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ular hypertrophy [49]. Left ventricular diastolic dysfunction often occurs in right ventricular hypertrophy and reflects the degree of right ventricular overload and septal distortion seen with pulmonary hypertension. This diastolic left ventricular dysfunction may be caused by abnormal relaxation of the interventricular septum, which, in cases of severe pulmonary hypertension, functions as part of the right ventricle rather than as part of the left ventricle. More recent studies, however, suggest that the abnormal diastolic transmitral Doppler flow patterns may stem from relative underfilling of the left ventricle in the setting of low right ventricular cardiac output [50]. In addition, the transmitral Doppler diastolic E to A ratio seems to correlate directly with cardiac output and inversely with pulmonary artery pressure (Fig. 10A, B) [50]. As with pulmonary embolism, in right ventricular overload with CTEPH the interventricular septum is often flattened in the parasternal shortaxis TTE view and may actually bulge into the left ventricle. The timing of this septal distortion helps distinguish between pressure and volume right ventricular overload. In pure right ventricular volume overload, the right ventricular diastolic pressure may equal or exceed that within the left ventricle, whereas the systolic pressure of the left ventricle greatly exceeds that of the right ventricle. Therefore, the interventricular septum flattens during diastole but returns to its normal curvature
Fig. 9. M-mode echocardiogram of the pulmonic valve in severe pulmonary hypertension. A characteristic W-shaped motion of the valve (the flying-W sign) is present during systole.
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Fig. 10. (A) Inverse correlation between transmitral E/A ratio and mean pulmonary artery (PA) pressure in patients before and after pulmonary thromboendarterectomy. (B) Direct correlation between transmitral E/A ratio and cardiac output (CO) in patients before and after pulmonary thromboendarterectomy. (From Mahmud E, Raisinghani A, Hassankhani A, Sadeghi SM, Strachen GM, Auger A, et al. Correlation of left ventricular diastolic filling characteristics with right ventricular overload and pulmonary artery pressure in chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol 2002;40:318–24; with permission).
during systole (Fig. 11A, B). With right ventricular pressure overload, however, the abnormally high right ventricular pressures persist through the entire cardiac cycle, and the interventricular septum remains deformed during both systole and diastole (Fig. 12A, B) [51]. This septal distortion can be quantified using the eccentricity index, a ratio of the two minor axes of the left ventricle measured in the parasternal short-axis plane. Normally, the left ventricle eccentricity index is 1.0 during both systole and diastole (ie, the left ventricle is circular in cross-section throughout
the cardiac cycle). In cases of right ventricular volume overload, the eccentricity index is abnormal during diastole (when the interventricular septum bulges toward the left ventricle) but returns to normal during systole. In right ventricular pressure overload, the eccentricity index is abnormal throughout the cardiac cycle, reflecting persistent septal deformation. The left atrium may appear compressed in the transverse plane because of leftward bulging of the interatrial septum. The mitral valve annulus may also be distorted by enlargement of the right
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Fig. 11. (A) Parasternal short-axis diastolic image in right ventricular volume overload. The interventricular septum is flattened and bulges toward the left. LV, left ventricle; RV, right ventricle. (B) Parasternal short-axis systolic image in right ventricular volume overload. The interventricular septum appears normal and is rounded toward the right, reflecting the much higher pressure in the left ventricle (LV) compared with the right ventricle (RV).
ventricle, and the mitral valve may sometimes prolapse into the left atrium during systole (even though the mitral valve is morphologically normal). Relief of pulmonary hypertension often eliminates this finding of pseudoprolapse [52].
coronary sinus dilation frequently accompanies pulmonary hypertension, correlating with right atrial pressure and size [54].
Differential diagnosis of chronic pulmonary hypertension Pericardium A significant proportion of patients with chronic pulmonary hypertension have pericardial effusions. Effusion size has been linked with right atrial pressure and is probably cause by impaired lymphatic and venous drainage [53]. Similarly,
Echocardiography can reliably differentiate various causes of pulmonary hypertension secondary to elevated left atrial pressure, including mitral and aortic valvular disease, cardiomyopathy, constrictive pericarditis, and cor triatriatum. In addition, contrast echocardiography using
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Fig. 12. (A) Parasternal short-axis diastolic image in right ventricular pressure overload. The interventricular septum is flattened and bulges toward the left. LV, left ventricle; RV, right ventricle. (B) Parasternal short-axis systolic image in right ventricular pressure overload. The interventricular septum remains flattened and continues to bulge toward the left, reflecting the abnormally elevated pressure in the right ventricle (RV) during systole. LV, left ventricle.
intravenous agitated saline can detect intracardiac shunts leading to pulmonary hypertension. In the absence of left-heart disease or intracardiac shunts, chronic pulmonary hypertension is most often caused by either idiopathic pulmonary arterial hypertension (sporadic/familial or associated with diseases such as HIV or collagen vascular disease) or CTEPH. Echocardiographic differentiation between these two entities is problematic.
Several studies have shown different characteristics in these two patient groups using echocardiographic variables [55,56] and high-fidelity pulmonary artery pressure waveforms [57–59], but in a prospective evaluation of 142 consecutive admissions for undifferentiated symptomatic pulmonary hypertension, echocardiography was unable to distinguish one group from the other reliably [60]. Therefore, other diagnostic tests such as V/Q
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scanning, spiral CT, and pulmonary angiography are recommended for definitive diagnosis of CTEPH versus pulmonary arterial hypertension. Utility of echocardiography for prognosis and treatment of chronic pulmonary hypertension Echocardiography plays an important role in predicting the prognosis of patients with pulmonary hypertension. For example, Raymond et al [2] found that pericardial effusion, right atrial enlargement and interventricular septal distortion predicted adverse outcomes in primary pulmonary hypertension. Similarly, D’Alonzo et al [61] reported a worsened survival in patients with pulmonary arterial hypertension, with elevated pulmonary artery pressure, right atrial pressure, and decreased cardiac output found on echocardiographic examination. Eysmann [62] added a shortened pulmonary artery Doppler acceleration time to the list of echocardiographic parameters associated with poor survival in pulmonary arterial hypertension. Pulmonary arterial hypertension: use of echocardiography in diagnosis and management Pulmonary arterial hypertension remains a difficult disease to manage despite recent advances in drug therapy including intravenous epoprostenol [63] and, more recently, inhaled iloprost [64] and oral bosentan [65]. Preliminary studies also suggest an adjunctive role for oral sildenafil [66]. Prognosis remains poor, but echocardiography has proven useful in assessing response to therapy. In a study by Hinderliter et al [67] the echocardiographic characteristics of 81 patients with severe pulmonary arterial hypertension were followed prospectively for 12 weeks. Baseline echocardiographic measures of right ventricular end-diastolic area, eccentricity index, pericardial effusion size, and tricuspid regurgitation jet area were inversely correlated with baseline exercise capacity. After 12 weeks of intravenous prostacyclin infusion, right ventricular end-diastolic area, systolic and diastolic eccentricity index, and maximal VTR were improved. Quality of life was not significantly associated with echocardiographic findings, however, and Doppler echocardiography was unable to quantify accurately small changes in pulmonary artery pressure associated with prostacyclin therapy in individual patients. Despite these limitations, it seems reasonable that patients with primary pulmonary hypertension should undergo echocardiography at regular
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intervals to detect markers of poor prognosis. More aggressive therapy and lung transplant evaluation would then be indicated for these patients [2]. Chronic thromboembolic pulmonary hypertension In contrast to idiopathic pulmonary arterial hypertension (primary pulmonary hypertension), CTEPH is often markedly improved by pulmonary thromboendarterectomy. Several studies have demonstrated that the changes in the anatomic and physiologic abnormalities of pulmonary hypertension can be monitored by echocardiography. As mentioned previously, Sadeghi et al [42] found that the severity of tricuspid regurgitation generally lessened after pulmonary thromboendarterectomy, most notably in patients with marked decreases in pulmonary artery pressure. Additionally, measurements of right ventricular area and systolic function (eg, fractional area change) improve when right ventricular afterload is decreased by pulmonary thromboendarterectomy [4]. Some of these anatomic changes occur immediately after pulmonary thromboendarterectomy, but additional improvements are seen over time as the right ventricle remodels [3]. Right atrial size decreases significantly after pulmonary thromboendarterectomy [68], and both IVC diameter and pulmonary artery size return to nearly normal within 2 weeks after successful surgery [65,68]. The left ventricular eccentricity index returns to approximately 1.0 after pulmonary thromboendarterectomy, and both the E/A ratio and isovolumetric relaxation time normalize. Cardiac output increases significantly after surgery [4,50,69]. Mahmud et al [50] found that the transmitral E/A ratio can be used as a noninvasive marker of successful pulmonary thromboendarterectomy, because a postoperative E/A ratio of more than 1.5 correlates with both normal cardiac output and pulmonary artery pressure. Mild pulmonary hypertension The long-term prognosis of mild pulmonary hypertension is difficult to predict and varies with the causative factor. Therefore, a complete evaluation is recommended to exclude correctable causes in asymptomatic patients who are serendipitously diagnosed with mild pulmonary hypertension. In patients with unexplained mild pulmonary hypertension, serial echocardiographic examinations at 6- to 12-month intervals seem
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prudent; earlier evaluation is warranted if symptoms develop [41]. [3]
Transesophageal echocardiography in pulmonary hypertension TEE can be clinically useful in some cases of pulmonary hypertension. For example, Dittrich et al [3] reported modest success using TEE in the identification of pulmonary artery thrombus. TEE has also been used to assess the influence of pericardial constraint and adaptation in CTEPH [70]. Gorcsan et al [71] found that TEE revealed therapy-altering data in 25% of patients with severe pulmonary hypertension. Other techniques such as TTE, CT angiography, V/Q scintigraphy, and pulmonary angiography seem to be more useful in the diagnosis and management of pulmonary hypertension, however. Therefore, current guidelines do not recommend the routine use of TEE in pulmonary hypertension but reserve it for the subset of cases in which other diagnostic studies are equivocal.
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[5]
[6]
[7]
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Summary Pulmonary vascular disease is an entity of diverse causes and varied morphologic and physiologic derangements. Echocardiography has evolved into a primary clinical tool for the diagnosis and management of pulmonary vascular disease and pulmonary hypertension. Echocardiography can help quantify right-heart function, right atrial and ventricular pressures, left ventricular function, and responses to treatment. The role of echocardiography in this area continues to evolve. Areas of active investigation include threedimensional echocardiographic assessment of right ventricular function, noninvasive analysis of right ventricular myocardial strain, and characterization of right ventricular function using tissue Doppler imaging [72].
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Echocardiography in pulmonary vascular disease Lori B. Daniels, MDa,b, David E. Krummen, MDa,b, Daniel G. Blanchard, MD, FACCa,b,* a
Division of Cardiology, Department of Medicine, University of California, San Diego School of Medicine, University of California, San Diego, 200 West Arbor Drive, San Diego, CA 92103, USA b University of California, San Diego Medical Center, 200 West Arbor Drive San Diego, CA 92103, USA
The assessment of pulmonary artery pressure, right ventricular function, right ventricular filling pressure, and tricuspid regurgitation provides invaluable information in the care of patients with pulmonary vascular disease. Echocardiography provides a rapid, noninvasive, portable, and accurate method to evaluate these parameters and also provides information on left ventricular and valvular function. Echocardiography has therefore become one of the most commonly performed diagnostic studies in patients with pulmonary vascular disease, and the technique’s applications in this area are likely to grow. This article presents an overview of the current uses of echocardiography in pulmonary vascular disease and pulmonary hypertension.
Echocardiographic measurements in pulmonary hypertension Measurement of right ventricular volume and function Measurement of right ventricular volume and function is important in making the diagnosis of pulmonary hypertension, but, because of the complex three-dimensional shape of the right ventricle, accurate measurement of right ventricular size and ejection fraction is difficult. In the apical four-chamber view, enlargement of the right ventricle can be determined qualitatively * Corresponding author. UCSD Medical Center, 200 W. Arbor Drive, #8411, San Diego, CA 92103. E-mail address: [email protected] (D.G. Blanchard).
when its chamber cross-sectional area exceeds that of the left ventricle (Fig. 1). In addition, right ventricular enlargement is present when the distal portion of the right ventricle shares space with the left ventricle at the cardiac apex in the apical four-chamber view. Normally, the cardiac apex is exclusively composed of left ventricular myocardium. Quantitative measurements of right ventricle size, thickness, and cross-sectional area can also be obtained [1]. Right ventricular systolic function can be expressed as the percent of change in right ventricular area during the cardiac cycle: ð½EDA ESA EDAÞ 100% EDA is the right ventricular area from the apical four-chamber view at end-diastole, and ESA is the right ventricular area at end-systole. Normal right ventricular fractional area change is 40% to 45% [2]. Because right ventricular functional measurement is highly dependent upon afterload and transseptal pressure gradients, the percent of change in cross-sectional area is not routinely quantified [3]. Tricuspid regurgitation Tricuspid regurgitation is often present in the setting of pulmonary hypertension and ranges from mild to severe. Tricuspid regurgitation may be caused by dilatation of the tricuspid annulus and morphologic alteration of right ventricular geometry [4] as well as by chordal traction of the valve leaflets [5]. Although the severity of tricuspid regurgitation does not necessarily correlate with the degree of pulmonary hypertension, reversal of pulmonary hypertension leads to
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artery systolic pressure is first to record the maximum tricuspid regurgitant jet velocity (VTR). This velocity can then be translated into the pressure gradient between the right ventricle and right atrium using the modified Bernoulli equation. The accuracy of this method depends on obtaining the true maximum VTR. The interrogating Doppler ultrasound beam must be parallel (or nearly so) to the direction of blood flow in the jet of TR (Fig. 2). The apical or right ventricular inflow views are most commonly used for this analysis. The peak right ventricular and pulmonary artery systolic pressure can then be calculated (in the absence of pulmonic stenosis) as Fig. 1. Apical four-chamber view in severe pulmonary hypertension. The right atrium (RA) and ventricle are markedly enlarged, and the right ventricle (RV) is hypertrophied. The interventricular septum is shifted leftward, and the left-heart chambers appear compressed.
significantly decreased tricuspid regurgitation in many cases, especially when the tricuspid regurgitation is caused by annular dilatation [6]. Estimation of pulmonary arterial pressure by the Bernoulli equation Transthoracic echocardiography (TTE) provides a readily available, noninvasive assessment of right-sided intracardiac pressures. The most reliable approach for approximating pulmonary
Pulmonary artery pressure ¼ 4VTR2 þ right atrial pressure ½7: Right atrial pressure can be estimated from the size and variation in the inferior vena cava (IVC) during quiet respiration. Best visualized from a subcostal window, the IVC normally has a diameter of 1.2 to 2.3 cm (Fig. 3) and should collapse by at least 50% during inspiration [8]. IVC dilation (or lack of collapse during inspiration) correlates with a higher right atrial pressure (eg, 10–15 mm Hg) [7]. In the setting of a dilated IVC, a complete lack of variation in IVC diameter with quick inspiration (a sniff) suggests a right atrial pressure of at least 20 mm Hg. Pulmonary artery diastolic pressure also can be estimated from the velocities of the pulmonic
Fig. 2. Continuous-wave spectral Doppler tracing of tricuspid regurgitation (TR) recorded in a modified apical fourchamber plane. The peak velocity of the TR jet is 5.2 m/s, suggesting a gradient of 108 mm Hg.
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nary hypertension include a decrease in the velocity-time integral of flow through the pulmonic valve and a shortening of the acceleration time (measured from beginning of flow through the pulmonic valve to peak velocity.) The acceleration time (AT, in milliseconds) can be used to estimate the mean pulmonary artery pressure in mm Hg [11,12] according to the equation Mean pulmonary artery pressure ¼ 80 ðAT=2Þ:
Acute pulmonary embolus Fig. 3. Subcostal view of the inferior vena cava (IVC) emptying into the right atrium (RA). A hepatic vein is also visible (arrow).
regurgitant Doppler tracing [9,10] (Fig. 4). Again, using the modified Bernoulli equation, the enddiastolic velocity of the pulmonic regurgitation jet can be used to calculate the instantaneous gradient between the pulmonary artery and the right ventricle. The pulmonary artery diastolic pressure is obtained by adding this calculated gradient to the estimated right atrial pressure. Other findings in right ventricular dysfunction and pulmonary hypertension Other characteristic Doppler abnormalities seen in right ventricular dysfunction and pulmo-
Typical findings on transthoracic echocardiography Depending on the size of the thromboembolus, patients with acute pulmonary embolism may have a number of abnormalities on TTE. Rarely, a large thrombus may be directly visualized in a proximal pulmonary artery or in transit in the right-heart chambers (Fig. 5A–C) [13]. The most common echocardiographic findings, however, are caused by acute right-sided pressure overload. With acute massive pulmonary embolism, the right ventricle dilates and becomes markedly hypokinetic. Abnormal motion of the interventricular septum with flattening or bulging toward the left ventricle in diastole may be seen (Fig. 6). Such paradoxical septal motion can result in left ventricular diastolic impairment, with decreased early diastolic filling
Fig. 4. Spectral Continuous-Wave Doppler tracing of pulmonic insufficiency (measured in the parasternal short-axis view at the base of the heart). The end-diastolic velocity is 2.2 m/s, suggesting a gradient between the pulmonary artery and right ventricle of 19 mm Hg at end-diastole.
Fig. 5. (A) Parasternal short-axis transthoracic echo image of a large thrombus (T) lodged in the bifurcation of the right and left main pulmonary arteries. Ao, ascending aorta; PA, main pulmonary artery. (B) Subcostal four-chamber view of a serpentine right atrial thrombus (**). On real-time imaging, the thrombus was very mobile. LV, left ventricle; RV, right ventricle. (C) Transesophageal image of a thrombus in transit. A venous thromboembolus has traveled to the right atrium (RA) and is lodged in a patent foramen ovale. A portion of the thrombus extends into the left atrium (LA).
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and increased reliance on the atrial kick (this process has been called the reverse Bernheim phenomenon) [14,15]. On Doppler examination of transmitral diastolic blood flow, this phenomenon is seen as a decrease in the early rapid filling velocity (E wave) and an increase in the atrial contraction velocity (A wave). This septal impairment of left ventricular diastolic filling may further contribute to the low cardiac output seen in cases of massive pulmonary embolism. A ratio of right ventricle–to–left ventricle enddiastolic diameter (measured in the parasternal or subcostal view) greater than the upper normal limit of 0.6 helps indicate right ventricular dysfunction and may distinguish between massive and nonmassive pulmonary embolism [16,17]. In addition, tricuspid regurgitation is common in acute pulmonary embolism (Fig. 7) and provides a useful way to assess pulmonary artery pressure. The right atrium and the IVC often dilate in acute massive pulmonary embolism, reflecting elevated right-sided pressures, and the IVC fails to collapse normally during inspiration. Interatrial shunting can occur if a patent foramen ovale is present and right ventricular pressure is significantly elevated. Unfortunately, the Doppler and two-dimensional echocardiographic findings of right ventricular dysfunction and right-sided pressure overload are not specific for pulmonary embolism: other diseases, including primary pulmonary hypertension, right ventricular myocardial infarction, cardiomyopathy, or right ventricular dysplasia, or acute exacerbations of obstructive pulmonary dis-
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ease may produce similar findings. Hypokinesis of the right ventricle free wall with sparing of apical function (McConnell’s sign) has been proposed as a relatively specific sign of right ventricular dysfunction caused by acute pulmonary embolism rather than other causes, but the overall clinical utility of this observation is debatable [18]. The degree of pulmonary hypertension seen with acute pulmonary embolism is usually mild to moderate, but right ventricular dysfunction is not universally present in acute pulmonary embolism [19]. Approximately 20% of patients with acute pulmonary embolism confirmed by ventilationperfusion (V/Q) scan or angiography may have normal findings on TTE [20,21]. Visualization of the right and left pulmonary arteries is sometimes difficult, and detection of pulmonary thromboemboli is unusual in most cases of pulmonary embolism. Furthermore, echocardiographic images may be of limited usefulness in patients who are obese, have hyperinflated lungs, or are immobile (including those on mechanical ventilators). Because of these limitations, TTE is not recommended as a primary diagnostic tool in acute pulmonary embolism. Nonetheless, it may be helpful in diagnosing or excluding alternative causes of sudden hemodynamic instability, including cardiac tamponade, aortic dissection, and acute valvular insufficiency [22]. Typical findings on transesophageal echocardiography Transesophageal echocardiography (TEE) can detect all the findings detected by TTE but is much more effective in the direct visualization of thrombi in the central pulmonary arteries. TEE visualizes the main pulmonary artery and the right pulmonary artery well, although the intervening left main bronchus may obscure the left pulmonary artery In the appropriate clinical setting, the finding of an intraluminal pulmonary artery mass is reasonably specific for the diagnosis of acute pulmonary embolism [7–9,23,24]. The sensitivity of TEE in acute pulmonary embolism varies among studies and depends on operator expertise and patient selection. False-positive results, however, are distinctly unusual [7–9,24]. Uses of echocardiography in acute pulmonary embolism
Fig. 6. Short-axis view in right ventricular overload. The interventricular septum is flattened and pushed toward the left ventricle. LV, left ventricle; RV, right ventricle.
Although TTE is not the recommended diagnostic test for pulmonary embolism, it nonetheless can play a major role in the assessment of
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Fig. 7. Short-axis view through the base of the heart showing significant tricuspid regurgitation. A multicolored jet of tricuspid regurgitation is seen in the right atrium (RA) during systole. LV, left ventricle; RV, right ventricle.
prognosis and management of this condition. Echocardiographic analysis of right ventricular function has proven useful in the risk stratification of patients with pulmonary embolism. In a recent study of 209 consecutive patients with pulmonary embolism, the 65 who were hemodynamically stable but had right ventricular dysfunction on TTE had an in-hospital mortality rate of 5% versus 0% in those without right ventricular dysfunction [25]. In another study of 126 consecutive pulmonary embolism patients, echocardiography emerged as the strongest predictor of in-hospital mortality, because the risk of in-hospital death was six times greater for the patients with right ventricular dysfunction than for those with normal right ventricular function [21]. At 1-year follow-up, there was still a 2.4 relative risk of mortality associated with right ventricular dysfunction. In patients without an underlying malignancy, the pulmonary embolism mortality rate was 7.7% in patients with right ventricular hypokinesis but 0% in those without right ventricular dysfunction. Right ventricular hypokinesis on baseline echocardiography was also an important predictor of increased mortality in the International Cooperative Pulmonary Embolism Registry. Right ventricular hypokinesis was associated with a twofold increase in mortality and was as important a predictor of poor outcome as advanced age, cancer, congestive heart failure, and renal insufficiency [26]. Finally, in the Manage-
ment, Strategy and Prognosis of Pulmonary Embolism Registry (MAPPET) study of 1001 patients, right ventricular dysfunction was an independent and significant marker of increased mortality [27]. Whether right ventricular dysfunction should be used to determine which patients receive thrombolytic therapy remains controversial. There is a general consensus that thrombolysis is the treatment of choice in patients with massive pulmonary embolism accompanied by hemodynamic collapse, and in these patients echocardiography is useful for monitoring changes in cardiac function with treatment [28]. There is, however, a significant subset of patients with acute pulmonary embolism (as high as 40%) who do not have significant hemodynamic compromise but still exhibit right ventricular dysfunction on TTE [25,26]. These patients may benefit from thrombolytic therapy. In a randomized trial of thrombolysis plus anticoagulation versus anticoagulation alone, Goldhaber et al [28] found that 5 of 23 patients with right ventricular hypokinesis and dilatation had recurrent pulmonary embolism after receiving intravenous heparin alone, whereas pulmonary embolism did not recur in any of the 23 patients with right ventricular dysfunction who received thrombolytics. Patients given thrombolytics also had greater recovery of right ventricular function at 24 hours, improved absolute pulmonary perfusion, and decreased right ventricular end-diastolic
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area, though overall mortality was unchanged [28]. In the MAPPET registry, Konstantinides et al [27,29] found a lower 30-day mortality in subgroup of 719 normotensive patients with pulmonary embolism and right ventricular overload who were treated with thrombolytics than in those treated with intravenous heparin alone (4.7% mortality in the 169 patients initially treated with thrombolytics versus 11.1% in the 550 patients who initially received anticoagulation alone, P = 0.016). Other studies, however, have had conflicting results. A recent study by Hamel et al [30] assessed 128 patients with massive pulmonary embolism, stable hemodynamics, and right ventricular dysfunction. In their analysis, treatment with low-molecular-weight heparin resulted in a trend toward decreased mortality compared with treatment with thrombolytics (0% versus 6.3%, P = 0.12), with fewer major bleeding events. Overall, it seems that patients with acute pulmonary embolism and right ventricular dysfunction detected on echocardiography represent a group at higher risk [31]. These patients merit aggressive therapy, but it is not completely clear whether the addition of thrombolytics decreases the risk of early death. Another subgroup of patients who may benefit from echocardiography is those presenting with acute pulmonary embolism and significant pulmonary hypertension (pulmonary artery systolic pressure >50 mm Hg). In a 5-year study of 78 patients with pulmonary embolism, Ribeiro et al [32] found that this degree of initial pulmonary hypertension conferred an odds ratio of 3.3 for persistent pulmonary hypertension or right ventricular dysfunction. They reported an early exponential rate of decline in pulmonary artery pressures, followed by a stable period after 6 weeks. In this study, 5% of patients with acute pulmonary embolism developed persistent cardiopulmonary disability and chronic right-heart dysfunction, a percentage higher than previously estimated [33–35]. Thus, follow-up echocardiography at 6 weeks can identify the high-risk subgroup of patients with persistent pulmonary hypertension and right ventricular dysfunction who are potential candidates for pulmonary thromboendarterectomy [36]. Recommendations for transthoracic echocardiography in acute pulmonary embolism As discussed previously, many patients with acute pulmonary embolism have normal echocar-
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diograms, and the routine use of TTE for diagnosis of pulmonary embolism is not recommended. Echocardiography may be appropriate, however, when the diagnosis is in question. In such cases, pulmonary embolism may be confirmed or another cause of the patient’s symptoms may be detected. Additionally, TTE is indicated in patients with confirmed pulmonary embolism, because the finding of right atrial or right ventricular thrombi often mandates the use of thrombolytics to prevent recurrent and potentially fatal pulmonary embolism. In hemodynamically unstable patients with suspected pulmonary embolism, TTE can be used as a rapid initial test. If significant right ventricular dysfunction is present, pulmonary embolism is likely. Finally, echocardiography can help monitor treatment response in patients with documented acute pulmonary embolism. Serial echocardiography can predict the development of CTEPH and canassesssuitabilityforfuturepulmonarythromboendarterectomy. Use of transesophageal echocardiography Only a few studies have examined the role of TEE in acute pulmonary embolism. In patients with suspected acute pulmonary embolism who present with shock or recent cardiopulmonary resuscitation, completion of standard diagnostic tests such as V/Q scanning, CT, and pulmonary angiography can be difficult. In these critically ill patients, bedside TEE may be useful. For example, a study of TEE in 25 patients presenting with pulseless electrical activity found that 14 had isolated right ventricular enlargement. Of these, 9 had acute pulmonary emboli [37]. One recent report by Krivec et al [38] examined 24 critically ill patients with unexplained shock and jugular venous distention. They found that 17 patients (70%) had right ventricular dilatation with global hypokinesis. TEE examination detected proximal pulmonary emboli in 12 of these patients and reduced right pulmonary artery flow in one additional patient. Of these 13 patients, 12 eventually had documentation of massive pulmonary embolism (either by V/Q scan or post mortem study). The few studies available suggest that TEE can provide direct visualization of proximal pulmonary arterial thrombi and so can be useful for determining surgical accessibility in patients with massive pulmonary embolism and refractory circulatory collapse.
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Echocardiography in chronic right ventricular overload and pulmonary hypertension The nonspecific nature of symptoms from chronic pulmonary hypertension often impedes the early diagnosis of the condition. For example, Rubin et al [39] reported a mean time from presentation to diagnosis of approximately 2 years in patients with pulmonary hypertension. In general, pulmonary vascular disease should be suspected when symptoms of dyspnea cannot be easily explained. When pulmonary hypertension is suspected from physical examination or screening tests (such as electrocardiography or chest radiographs), Doppler echocardiography is the best subsequent test to evaluate right-heart function and pressure. In many cases, TTE is the first test to detect an elevation of right ventricular pressure [40]. TTE also provides important information about prognosis and response to treatment in these patients [3,41]. Echocardiographic features of chronic pulmonary hypertension Tricuspid valve As noted previously, tricuspid regurgitation is common in the setting of pulmonary hypertension but may regress with reversal of the pressure overload. A recent study by Sadeghi et al [42] evaluated patients with CTEPH and severe tricuspid regurgitation who subsequently underwent pulmonary thromboendarterectomy. Seventy per-
cent of the patients had resolution of tricuspid regurgitation after pulmonary thromboendarterectomy, often despite persistent tricuspid annular dilation. The 30% of patients with persistent severe tricuspid regurgitation had less postoperative decrease in pulmonary artery pressure. Thistlethwaite et al [43] reported that intraoperative classification of pulmonary thromboembolic disease helps predict successful decreases in pulmonary artery pressure and tricuspid regurgitation severity in patients with CTEPH: those with thrombus in the main lobar pulmonary arteries had the greatest improvement in these parameters following pulmonary thromboendarterectomy. Inferior vena cava and right-heart chambers As described previously, the right atrium and IVC are commonly dilated in patients with pulmonary hypertension (Fig. 8). This dilation is generally a manifestation of significant tricuspid regurgitation, elevated right ventricular diastolic pressure, or both. Additionally, elevation of right atrial pressure may cause the interatrial septum to bulge toward the left atrium. Right atrial pressure in chronic pulmonary hypertension can be estimated by means similar to the method described for acute pulmonary embolism. The pulmonary artery is often dilated in the setting of chronic pulmonary hypertension and right ventricular hypertrophy. Pulmonic valvular regurgitation frequently occurs as well, and, as noted previously, the regurgitant flow velocity can
Fig. 8. Subcostal view demonstrating a dilated inferior vena cava (IVC). Diameter of the IVC is more than 2.5 cm. LA, left atrium; RA, right atrium.
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be used to estimate the pulmonary artery diastolic pressure [9,10]. M-mode examination of the pulmonic valve in pulmonary hypertension may show a characteristic W-shaped motion of the valve leaflet during systole [44–46]. This midsystolic closure of the valve and partial reopening in late systole, sometimes called the flying-W sign (Fig. 9), is probably caused by elevated pulmonary vascular resistance and early reflection of the systolic pressure wave within the proximal pulmonary arteries [47]. There also may be a loss of the normal presystolic opening of the pulmonic valve with atrial contraction (the ‘‘a’’ dip). Because of the large difference between right ventricular pressure and pulmonary artery pressure throughout diastole, the pressure generated by the atrial kick is insufficient to open the pulmonic valve even partially. Chronic pulmonary hypertension ultimately leads to right ventricular hypertrophy, enlargement, and depressed systolic function. Echocardiographic measurements of right ventricle wall thickness can be performed from the parasternal and subcostal views, and a value of more than 5 mm is diagnostic for right ventricular hypertrophy [48]. In the setting of right ventricular hypertrophy, the moderator band is often hypertrophied and thickened as well [3]. Left-heart chambers and interventricular septum The left ventricle size is normal to small in severe pulmonary hypertension and right ventric-
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ular hypertrophy [49]. Left ventricular diastolic dysfunction often occurs in right ventricular hypertrophy and reflects the degree of right ventricular overload and septal distortion seen with pulmonary hypertension. This diastolic left ventricular dysfunction may be caused by abnormal relaxation of the interventricular septum, which, in cases of severe pulmonary hypertension, functions as part of the right ventricle rather than as part of the left ventricle. More recent studies, however, suggest that the abnormal diastolic transmitral Doppler flow patterns may stem from relative underfilling of the left ventricle in the setting of low right ventricular cardiac output [50]. In addition, the transmitral Doppler diastolic E to A ratio seems to correlate directly with cardiac output and inversely with pulmonary artery pressure (Fig. 10A, B) [50]. As with pulmonary embolism, in right ventricular overload with CTEPH the interventricular septum is often flattened in the parasternal shortaxis TTE view and may actually bulge into the left ventricle. The timing of this septal distortion helps distinguish between pressure and volume right ventricular overload. In pure right ventricular volume overload, the right ventricular diastolic pressure may equal or exceed that within the left ventricle, whereas the systolic pressure of the left ventricle greatly exceeds that of the right ventricle. Therefore, the interventricular septum flattens during diastole but returns to its normal curvature
Fig. 9. M-mode echocardiogram of the pulmonic valve in severe pulmonary hypertension. A characteristic W-shaped motion of the valve (the flying-W sign) is present during systole.
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Fig. 10. (A) Inverse correlation between transmitral E/A ratio and mean pulmonary artery (PA) pressure in patients before and after pulmonary thromboendarterectomy. (B) Direct correlation between transmitral E/A ratio and cardiac output (CO) in patients before and after pulmonary thromboendarterectomy. (From Mahmud E, Raisinghani A, Hassankhani A, Sadeghi SM, Strachen GM, Auger A, et al. Correlation of left ventricular diastolic filling characteristics with right ventricular overload and pulmonary artery pressure in chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol 2002;40:318–24; with permission).
during systole (Fig. 11A, B). With right ventricular pressure overload, however, the abnormally high right ventricular pressures persist through the entire cardiac cycle, and the interventricular septum remains deformed during both systole and diastole (Fig. 12A, B) [51]. This septal distortion can be quantified using the eccentricity index, a ratio of the two minor axes of the left ventricle measured in the parasternal short-axis plane. Normally, the left ventricle eccentricity index is 1.0 during both systole and diastole (ie, the left ventricle is circular in cross-section throughout
the cardiac cycle). In cases of right ventricular volume overload, the eccentricity index is abnormal during diastole (when the interventricular septum bulges toward the left ventricle) but returns to normal during systole. In right ventricular pressure overload, the eccentricity index is abnormal throughout the cardiac cycle, reflecting persistent septal deformation. The left atrium may appear compressed in the transverse plane because of leftward bulging of the interatrial septum. The mitral valve annulus may also be distorted by enlargement of the right
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Fig. 11. (A) Parasternal short-axis diastolic image in right ventricular volume overload. The interventricular septum is flattened and bulges toward the left. LV, left ventricle; RV, right ventricle. (B) Parasternal short-axis systolic image in right ventricular volume overload. The interventricular septum appears normal and is rounded toward the right, reflecting the much higher pressure in the left ventricle (LV) compared with the right ventricle (RV).
ventricle, and the mitral valve may sometimes prolapse into the left atrium during systole (even though the mitral valve is morphologically normal). Relief of pulmonary hypertension often eliminates this finding of pseudoprolapse [52].
coronary sinus dilation frequently accompanies pulmonary hypertension, correlating with right atrial pressure and size [54].
Differential diagnosis of chronic pulmonary hypertension Pericardium A significant proportion of patients with chronic pulmonary hypertension have pericardial effusions. Effusion size has been linked with right atrial pressure and is probably cause by impaired lymphatic and venous drainage [53]. Similarly,
Echocardiography can reliably differentiate various causes of pulmonary hypertension secondary to elevated left atrial pressure, including mitral and aortic valvular disease, cardiomyopathy, constrictive pericarditis, and cor triatriatum. In addition, contrast echocardiography using
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Fig. 12. (A) Parasternal short-axis diastolic image in right ventricular pressure overload. The interventricular septum is flattened and bulges toward the left. LV, left ventricle; RV, right ventricle. (B) Parasternal short-axis systolic image in right ventricular pressure overload. The interventricular septum remains flattened and continues to bulge toward the left, reflecting the abnormally elevated pressure in the right ventricle (RV) during systole. LV, left ventricle.
intravenous agitated saline can detect intracardiac shunts leading to pulmonary hypertension. In the absence of left-heart disease or intracardiac shunts, chronic pulmonary hypertension is most often caused by either idiopathic pulmonary arterial hypertension (sporadic/familial or associated with diseases such as HIV or collagen vascular disease) or CTEPH. Echocardiographic differentiation between these two entities is problematic.
Several studies have shown different characteristics in these two patient groups using echocardiographic variables [55,56] and high-fidelity pulmonary artery pressure waveforms [57–59], but in a prospective evaluation of 142 consecutive admissions for undifferentiated symptomatic pulmonary hypertension, echocardiography was unable to distinguish one group from the other reliably [60]. Therefore, other diagnostic tests such as V/Q
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scanning, spiral CT, and pulmonary angiography are recommended for definitive diagnosis of CTEPH versus pulmonary arterial hypertension. Utility of echocardiography for prognosis and treatment of chronic pulmonary hypertension Echocardiography plays an important role in predicting the prognosis of patients with pulmonary hypertension. For example, Raymond et al [2] found that pericardial effusion, right atrial enlargement and interventricular septal distortion predicted adverse outcomes in primary pulmonary hypertension. Similarly, D’Alonzo et al [61] reported a worsened survival in patients with pulmonary arterial hypertension, with elevated pulmonary artery pressure, right atrial pressure, and decreased cardiac output found on echocardiographic examination. Eysmann [62] added a shortened pulmonary artery Doppler acceleration time to the list of echocardiographic parameters associated with poor survival in pulmonary arterial hypertension. Pulmonary arterial hypertension: use of echocardiography in diagnosis and management Pulmonary arterial hypertension remains a difficult disease to manage despite recent advances in drug therapy including intravenous epoprostenol [63] and, more recently, inhaled iloprost [64] and oral bosentan [65]. Preliminary studies also suggest an adjunctive role for oral sildenafil [66]. Prognosis remains poor, but echocardiography has proven useful in assessing response to therapy. In a study by Hinderliter et al [67] the echocardiographic characteristics of 81 patients with severe pulmonary arterial hypertension were followed prospectively for 12 weeks. Baseline echocardiographic measures of right ventricular end-diastolic area, eccentricity index, pericardial effusion size, and tricuspid regurgitation jet area were inversely correlated with baseline exercise capacity. After 12 weeks of intravenous prostacyclin infusion, right ventricular end-diastolic area, systolic and diastolic eccentricity index, and maximal VTR were improved. Quality of life was not significantly associated with echocardiographic findings, however, and Doppler echocardiography was unable to quantify accurately small changes in pulmonary artery pressure associated with prostacyclin therapy in individual patients. Despite these limitations, it seems reasonable that patients with primary pulmonary hypertension should undergo echocardiography at regular
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intervals to detect markers of poor prognosis. More aggressive therapy and lung transplant evaluation would then be indicated for these patients [2]. Chronic thromboembolic pulmonary hypertension In contrast to idiopathic pulmonary arterial hypertension (primary pulmonary hypertension), CTEPH is often markedly improved by pulmonary thromboendarterectomy. Several studies have demonstrated that the changes in the anatomic and physiologic abnormalities of pulmonary hypertension can be monitored by echocardiography. As mentioned previously, Sadeghi et al [42] found that the severity of tricuspid regurgitation generally lessened after pulmonary thromboendarterectomy, most notably in patients with marked decreases in pulmonary artery pressure. Additionally, measurements of right ventricular area and systolic function (eg, fractional area change) improve when right ventricular afterload is decreased by pulmonary thromboendarterectomy [4]. Some of these anatomic changes occur immediately after pulmonary thromboendarterectomy, but additional improvements are seen over time as the right ventricle remodels [3]. Right atrial size decreases significantly after pulmonary thromboendarterectomy [68], and both IVC diameter and pulmonary artery size return to nearly normal within 2 weeks after successful surgery [65,68]. The left ventricular eccentricity index returns to approximately 1.0 after pulmonary thromboendarterectomy, and both the E/A ratio and isovolumetric relaxation time normalize. Cardiac output increases significantly after surgery [4,50,69]. Mahmud et al [50] found that the transmitral E/A ratio can be used as a noninvasive marker of successful pulmonary thromboendarterectomy, because a postoperative E/A ratio of more than 1.5 correlates with both normal cardiac output and pulmonary artery pressure. Mild pulmonary hypertension The long-term prognosis of mild pulmonary hypertension is difficult to predict and varies with the causative factor. Therefore, a complete evaluation is recommended to exclude correctable causes in asymptomatic patients who are serendipitously diagnosed with mild pulmonary hypertension. In patients with unexplained mild pulmonary hypertension, serial echocardiographic examinations at 6- to 12-month intervals seem
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prudent; earlier evaluation is warranted if symptoms develop [41]. [3]
Transesophageal echocardiography in pulmonary hypertension TEE can be clinically useful in some cases of pulmonary hypertension. For example, Dittrich et al [3] reported modest success using TEE in the identification of pulmonary artery thrombus. TEE has also been used to assess the influence of pericardial constraint and adaptation in CTEPH [70]. Gorcsan et al [71] found that TEE revealed therapy-altering data in 25% of patients with severe pulmonary hypertension. Other techniques such as TTE, CT angiography, V/Q scintigraphy, and pulmonary angiography seem to be more useful in the diagnosis and management of pulmonary hypertension, however. Therefore, current guidelines do not recommend the routine use of TEE in pulmonary hypertension but reserve it for the subset of cases in which other diagnostic studies are equivocal.
[4]
[5]
[6]
[7]
[8]
Summary Pulmonary vascular disease is an entity of diverse causes and varied morphologic and physiologic derangements. Echocardiography has evolved into a primary clinical tool for the diagnosis and management of pulmonary vascular disease and pulmonary hypertension. Echocardiography can help quantify right-heart function, right atrial and ventricular pressures, left ventricular function, and responses to treatment. The role of echocardiography in this area continues to evolve. Areas of active investigation include threedimensional echocardiographic assessment of right ventricular function, noninvasive analysis of right ventricular myocardial strain, and characterization of right ventricular function using tissue Doppler imaging [72].
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