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(Chest. 2005;127:1836-1843.)
© 2005 American College of Chest Physicians

Pulmonary Arterial Hypertension*

The Key Role of Echocardiography

Eduardo Bossone, MD, PhD, FCCP; Bruno Dino Bodini, MD; Alfredo Mazza, MD, PhD and Luigi Allegra, MD

* From the Institute of Respiratory Disease (Drs. Bossone, Bodini, and Allegra), University of Milan, IRCCS Ospedale Maggiore, Milan; and Cardiology Department (Dr. Mazza), General Hospital, ASL AV1 Arlano Irpino, Italy.

Correspondence to: Eduardo Bossone, MD, PhD, FCCP, Director, Echocardiography Laboratory, National Research Council, Southern Italy, c/o ISBEM, Cittadella della Ricerca, S.S. 7 per Mesagne Km. 7+300, 72100 Brindisi, Italy; e-mail: bossone{at}isbem.cnrsm.it


   Abstract
TOP
 Abstract
Introduction
 Echocardiographic Features
 Prognostic Implications
 Ex-echo
 Future Directions
 Conclusions
 References
 
Given the nonspecific nature of its early symptoms and signs, pulmonary arterial hypertension (PAH) is often diagnosed in its advanced stages. Although clinical assessment is essential when initially evaluating patients with suspected PAH, echocardiography is a key screening tool in the diagnostic algorithm. It not only provides an estimate of pulmonary pressure at rest and during exercise, but it may also help to exclude any secondary causes of pulmonary hypertension, predict the prognosis, monitor the efficacy of specific therapeutic interventions, and detect the preclinical stage of the disease.

Key Words: echocardiography • exercise-induced pulmonary hypertension • pulmonary hypertension


   Introduction
TOP
 Abstract
 Introduction
Echocardiographic Features
 Prognostic Implications
 Ex-echo
 Future Directions
 Conclusions
 References
 
Pulmonary arterial hypertension (PAH)—mean pulmonary artery pressure (PAPm) > 25 mm Hg at rest, or > 30 mm Hg during exercise—defines a group of diseases characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular (RV) failure and death.12 PAH encompasses primary disease and disease related mainly to collagen vascular disease, congenital systemic-to-pulmonary shunts, portal hypertension, HIV infection, and drugs (anorexigens and cocaine) [Table 1 ].2


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  		Table 1.. Diagnostic Classification of PH*

 
Given the insidious symptoms of mild PAH, a high degree of clinical suspicion is required in order to make the diagnosis. Together with a careful clinical evaluation, a chest radiograph and ECG, a two-dimensional echocardiography (2D-echo) Doppler examination is considered a first-line diagnostic test.1234567 It not only provides an estimate of pulmonary artery pressures (PAPs) at rest and during exercise, but also helps to exclude valvular, primary myocardial and congenital causes of elevated right-sided pressure, and can monitor the effects of therapy.7891011 Recognizing the characteristic baseline echocardiographic and Doppler features of PAH is therefore of paramount importance in both the initial and serial evaluation of the patients.

The aim of the this review is to describe the echocardiographic features of PAH, discuss their prognostic implications, and illustrate the role of exercise Doppler echocardiography (Ex-echo) in the detection of latent or exercise-induced pulmonary hypertension (ExPH).


   Echocardiographic Features
TOP
 Abstract
 Introduction
 Echocardiographic Features
Prognostic Implications
 Ex-echo
 Future Directions
 Conclusions
 References
 
2D-echo
Because of chronic RV pressure overload, most patients present with enlarged right-side chambers, RV hypertrophy, and reduced global RV systolic function.9 This is accompanied by a systolic flattening of the interventricular septum (IVS), with increased thickness and an abnormal IVS/posterior left ventricular (LV) wall ratio (> 1) in response to pressure overload. The LV appears D-shaped with reduced diastolic and systolic volumes, but preserved global systolic function9 (Fig 1 , top). Pericardial effusion (PE) and mitral valve prolapse have also been described in PAH patients1213; the first may be a manifestation of impaired venous and lymphatic drainage secondary to elevated right atrial pressure,13 and the second has been related to a small LV and the possible involvement of leaflets affected by associated connective tissue disorder12 (Table 2 ).



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  		Figure 1.. Top: Apical four-chamber view (systole) showing enlarged right-side chambers with compressed and geometric distortion of an intrinsically normal LV secondary to marked RV pressure overload; severe TR. RA = right atrium; LA = left atrium. Bottom: Peak TR velocity of 4.68 m/s, with a peak gradient of 87.8 mm Hg indicating severe PH.

 

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  		Table 2.. M-mode, 2D-echo, and color Doppler Features of Patients With PAH*

 
Color-Doppler Echocardiography
Doppler echocardiography allows an accurate estimate of PAP as tricuspid regurgitation (TR) peak velocity and RV outflow tract (RVOT) acceleration time (AT) have linear positive and negative correlations with pulmonary artery systolic pressure (PASP) and PAPm1415161718192021 (Fig 1, bottom). Furthermore, the peak early diastolic and the end-diastolic velocities of pulmonary regurgitation correlate with PAPm and pulmonary artery end-diastolic pressure22 (Table 3 ). At the time of definite diagnosis, most PAH patients present at least moderate TR, with a PASP of ≥ 60 mm Hg.9 The development of TR is likely to be related to the presence of annular dilation, altered RV geometry, and the apical displacement of tricuspid leaflets.23 Significant pulmonary insufficiency may also be seen. The analysis of RVOT pulsed Doppler flow usually reveals an AT of < 100 ms, which reflects an abnormal PAPm.9 Finally, as a result of altered RV/LV interaction, LV diastolic dysfunction characterized by a marked dependence on atrial contraction for LV filling may also be present. As a direct effect of this phenomenon, atrial fibrillation may not be well tolerated and vasodilating therapy may have detrimental effects on diastolic LV loading.242526


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  		Table 3.. Noninvasive Assessment of Pulmonary Pressure by Doppler Echocardiography*

 

   Prognostic Implications
TOP
 Abstract
 Introduction
 Echocardiographic Features
 Prognostic Implications
Ex-echo
 Future Directions
 Conclusions
 References
 
The prognosis of PAH is relatively poor and directly related to the severity of right-heart dysfunction.12272829303132333435363738394041424344 Together with a number of hemodynamic and noninvasive parameters, the echocardiographic indicators of right-heart impairment (Table 4 ), which include indexed right atrial area, the degree of septal shift in diastole, a high Doppler RV performance index, and the severity of PE, have been associated with unfavorable outcomes (death or lung transplantation).649505152535455565758596061


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  		Table 4.. Echocardiographic Measures of RV Structure and Function in PH

 
Doppler echocardiography has also been used to monitor the efficacy of specific therapeutic interventions.811 In a double-blind, randomized, placebo-controlled trial, Galiè et al1011 evaluated the effects of the oral endothelin-receptor antagonist bosentan on the echocardiographic and Doppler parameters associated with RV and LV structure and function. In comparison with the placebo group, the patients treated with bosentan for 16 weeks had less RV dilatation, a larger LV, greater stroke volume, and a higher cardiac index. There was also an improvement in RV ejection and LV early diastolic filling, and beneficial effects on the diameter of the inferior vena cava and PE.1011


   Ex-echo
TOP
 Abstract
 Introduction
 Echocardiographic Features
 Prognostic Implications
 Ex-echo
Future Directions
 Conclusions
 References
 
Ex-echo is a reliable means of monitoring PAP during exercise and thus differentiating physiologic and pathologic pulmonary PAP responses.762636465 It can be used to assess the pulmonary vascular response to increasing blood flow and may help identify patients with ExPH. In healthy subjects, moderate exercise leads to an increase in stroke volume and a relatively small increase in PAP. Pulmonary vascular resistance falls with exercise as a physiologic response that allows the thin-walled RV to increase pulmonary blood flow.66676869707172 However, at peak workloads in well-trained athletes and lower levels of effort in subjects with impaired LV filling, the large increase in pulmonary blood flow may be accompanied by increased LV filling and left atrial pressure, which may contribute to the higher PAP responses observed in athletes.737475 Bossone et al76 demonstrated a higher physiologic range of pulmonary pressure responses during recumbent bicycle Ex-echo in highly conditioned hockey players (up to 60 mm Hg of PASP) than in healthy volunteers. A number of investigators have described subsets of patients with pathologic pulmonary pressure responses during exercise and normal pulmonary pressure at rest.626364 Given the absence of any specific symptoms or signs, ExPH is rarely considered, and a high degree of clinical suspicion is necessary in certain subsets of patients, such as in those with a history of pulmonary thromboemboli, mitral valve disease, the scleroderma spectrum of disorders, and familial primary pulmonary hypertension (PH). However, in these patients, resting transthoracic 2D-echo may show a distinct Doppler pattern of RVOT velocity curve suggesting a compromised vascular bed even with normal resting PASP. RVOT velocity curve indexes may also have diagnostic value in the early detection of ExPH.7778 It should be emphasized that more studies are needed for the following: (1) to define the full physiologic range of pulmonary pressure responses to exercise in relation to age and gender in athletes and nonathletes as a reference for adequate cardiovascular evaluation and counseling prior to engaging in vigorous exercise or resuming competition; and (2) to investigate the natural history of disorders complicated by PAH, especially in high-risk groups (eg, subjects with a history of repaired atrial septal defect, cirrhosis, collagen vascular diseases, HIV, the use of anorexigens) in order to clarify whether and when treatment is appropriate.7980 The latter is particularly important because of the availability of new drugs, such as endothelin antagonists, which improve hemodynamics and functional status in symptomatic World Health Organization class III and IV patients, and appear to improve prognosis.118182 Ex-echo may be an excellent means of assessing whether preclinical treatment can prevent the development of more severe forms of pulmonary vascular disease.80


   Future Directions
TOP
 Abstract
 Introduction
 Echocardiographic Features
 Prognostic Implications
 Ex-echo
 Future Directions
Conclusions
 References
 
The extensive application of new echocardiographic methods (pulsed-wave tissue Doppler imaging, contrast, tridimensional, and intracardiac echocardiography) may open up new horizons in the noninvasive assessment of RV function and structure in patients with PAH. Systolic and diastolic tissue Doppler imaging-derived velocity profiles of RV free wall and the lateral tricuspid annulus have been related to right chamber hemodynamic and function, and may be useful in detecting RV dysfunction early, which could have an important impact on treatment and prognosis.838485868788899091

Contrast echocardiography is an established and useful means of enhancing the faint Doppler tricuspid and pulmonary flow signals that are essential for determining PAP at rest and during exercise, identifying congenital systemic-to-pulmonary shunts (a definite cause of PAH), and improving the opacification and border delineation in patients with a suboptimally defined endocardial border such as those with COPD.92 Most recently, the transpulmonary passage of human albumin during dobutamine infusion has been applied to predict intracardiac pressure and clinical outcome in patients with congestive heart failure.93

By eliminating the need for geometric assumptions, three-dimensional echocardiography provides more accurate estimates of LV and RV volumes and the ejection fraction, and may provide new insights into RV and LV structure, function, and interdependence.9495969798 Intracardiac echocardiography provides comprehensive anatomic and physiologic data during cardiac surgery, and has been experimented as a guide for balloon atrial septostomy in end-stage PH with severe right atrial enlargement and the loss of anatomic landmarks.99

Finally, the following should be stressed: (1) the development of new ultrasound imaging equipment has decreased the number of technically inadequate studies and has simultaneously increased the accuracy of using 2D-echo PAP estimates in everyday clinical practice; and (2) the introduction of hand-carried cardiac ultrasound devices may have a substantial impact on PH screening in the community.100101102


   Conclusions
TOP
 Abstract
 Introduction
 Echocardiographic Features
 Prognostic Implications
 Ex-echo
 Future Directions
 Conclusions
References
 
Echocardiography is an essential component of the diagnostic algorithm of PAH insofar as it makes it possible to confirm the diagnosis. It may also help to exclude PH related to congenital systemic-to-pulmonary shunts or secondary to pulmonary venous hypertension, thromboembolic disease or obstructed pulmonary vessels, predict the prognosis, monitor the efficacy of specific therapeutic interventions, and detect the preclinical stage of the disease.


   Footnotes
 
Abbreviations: AT = acceleration time; Ex-echo = exercise Doppler echocardiography; ExPH = exercise-induced pulmonary hypertension; IVS = interventricular septum; LV = left ventricle/ventricular; PAH = pulmonary arterial hypertension; PAP = pulmonary artery pressure; PAPm = mean pulmonary artery pressure; PASP = pulmonary artery systolic pressure; PE = pericardial effusion; PH = pulmonary hypertension; RV = right ventricle/ventricular; RVOT = right ventricular outflow tract; TR = tricuspid regurgitation; 2D-echo = two-dimensional echocardiography

Received for publication January 5, 2004. Accepted for publication November 4, 2004.


   References
TOP
 Abstract
 Introduction
 Echocardiographic Features
 Prognostic Implications
 Ex-echo
 Future Directions
 Conclusions
 References
 

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