|Harold L Dauerman, MD
James P Morgan, MD, PhD
|May 10, 1998|
In addition, the peripheral vessels are attenuated, leading to oligemic lung fields. Right ventricular and right atrial dilatation are later findings that are seen as the disease progresses to right ventricular failure. Right ventricular enlargement can also lead to a decrease in the retrosternal space. However, these findings may be obscured in the presence of kyphoscoliosis, hyperinflated lungs, left ventricular enlargement, or interstitial lung disease.
Electrocardiogram ！ The electrocardiogram may demonstrate signs of right ventricular hypertrophy or strain (show ECG 1).
In acute pulmonary embolism, for example, a classic pattern of an S wave in lead I with a Q and inverted T wave in lead III may be seen. Findings that may be seen in chronic right ventricular overload include:
• Right axis deviation and R/S ratio greater than 1 in lead V1.
• Increased P wave amplitude in lead II (P pulmonale) due to right atrial enlargement (show figure 2
and show ECG 2).
• Incomplete or complete right bundle branch block.
Most electrocardiographic criteria show a high specificity (ie, the findings are absent in patients without the disease) but a low sensitivity (ie, the findings are present in patients with the disease) for the detection of RVH. The sensitivity of the electrocardiogram is even worse in patients with biventricular hypertrophy or COPD .
Two dimensional echocardiography ！ Most patients with PAH have two dimensional echocardiographic signs of chronic right ventricular pressure overload (show echocardiogram 1,
show echocardiogram 2,
and show echocardiogram 3).
The elevation in pressure leads to increased thickness of the right ventricle with paradoxical bulging of the septum into the left ventricle during systole (show figure 3).
At a later stage, right ventricular dilatation occurs and the septum shows abnormal diastolic flattening.
Stress on the right heart initially produces hyperkinesis. However, this is eventually followed by right ventricular hypokinesis, associated with right atrial dilatation and tricuspid regurgitation. The latter is not due to an intrinsic abnormality of the tricuspid valve; it is a secondary manifestation of dilatation of the tricuspid annulus and right ventricle .
Doppler echocardiography ！ Doppler echocardiography is the most reliable noninvasive estimation of the pulmonary artery pressure. This technique takes advantage of the functional tricuspid insufficiency usually present in PAH. The maximum tricuspid regurgitant jet velocity is recorded and the pulmonary artery pressure (PAP) is then calculated by the modified Bernoulli equation:
where RAP is the right atrial pressure estimated from the size and respiratory variation of flow in the inferior vena cava. Other findings associated with pulmonary hypertension are pulmonic insufficiency and midsystolic closure of the pulmonic valve [14,15]. (See "Principles of Doppler echocardiography").
The efficacy of Doppler echocardiography may be limited by the ability to identify an adequate tricuspid regurgitant jet. It may also be less sensitive because of alterations induced by the underlying disease. For example, acoustic windows in patients with COPD may be limited by the increased anteroposterior diameter of the chest.
Despite these potential problems, Doppler estimation using tricuspid regurgitation is far more sensitive than the clinical examination and can make an accurate diagnosis in the majority of patients. This is illustrated by the following observations:
• In one report, Doppler ultrasound examination was able to identify tricuspid regurgitation in 80 percent of 69 patients with catheterization-documented PAH (PA systolic pressure above 35 mmHg) . The accuracy was even higher in patients with more severe disease (PA systolic pressure above 50 mmHg). Tricuspid regurgitation was detected in 95 percent of these patients and there was a 97 percent correlation with the pressure measured by catheterization.
• Another study of 33 patients with severe COPD compared clinical and echocardiographic criteria in establishing the diagnosis of PAH . Echocardiographic cor pulmonale was said to be present when the right ventricular free wall thickness was >0.6 cm in the subxiphoid view, PA systolic pressure was greater than 40 mmHg by tricuspid jet Doppler with saline contrast, and the RV/LV ratio was increased. Clinical criteria included right ventricular hypertrophy on the electrocardiogram, enlarged pulmonary arteries on the chest x-ray, and physical findings such as a loud pulmonic heart sound, parasternal heave, jugular venous distension, edema, and hepatomegaly. Cor pulmonale was identified by clinical criteria in only 39 percent of patients versus 75 percent with echocardiography. The use of saline contrast significantly enhanced the sensitivity of Doppler ultrasound in detecting tricuspid regurgitation.
Exercise echocardiography ！ There is a group of patients with exertional symptoms in whom PAH can only be diagnosed with exercise. In this setting, exercise echocardiography is the noninvasive technique of choice. In one study of 36 patients with a variety of chronic lung diseases, for example, 28 percent of those with normal resting PA pressures had significant PAH after bicycle ergometry using saline enhanced contrast echocardiography . In 10 patients, simultaneous right heart catheterization showed a 98 percent correlation between exercise Doppler and catheterization estimates of pulmonary artery systolic pressure.
Pulmonary function tests ！ Pulmonary function tests should be performed in patients with a suggestive history of underlying lung disease and in those with normal cardiac function. An obstructive pattern is suggestive of COPD. These tests can also aid in the diagnosis of interstitial lung disease. It is important to appreciate that only severe interstitial lung disease (with lung volume below 50 percent of normal) produces SPAH, while a mild restrictive defect can be produced by PAH itself. Thus, the latter finding is not indicative of interstitial lung disease as a cause of SPAH.
Right-sided cardiac catheterization ！ Catheterization of the right heart is the gold standard for the diagnosis, quantification, and characterization of PAH (show radiograph 2).
This procedure is indicated only when the necessary information cannot be obtained with Doppler echocardiography. Current indications include:
• When echocardiography does not permit measurement of a tricuspid regurgitant jet, which does not exclude significant pulmonary artery hypertension .
• When symptoms are exertional and simultaneous measurement of left-sided pressures during exercise are indicated.
• When therapy will be determined by precise measurement of pulmonary vascular resistance and the response to vasodilators.
• For verification of the presence and severity of congenital and acquired left-to-right shunts, if the measurements are unclear from prior testing.
• When left heart catheterization is required as, for example, in the patient over 40 years of age or with risk factors for coronary disease who is a candidate for surgical repair of a shunt. In this setting, preoperative evaluation of the coronary arteries may be desirable.
Right heart catheterization can also be used to determine the potential reversibility of PAH using vasodilators such as nitroprusside, prostacyclin, or nitric oxide [19,20]. This information can be used to predict whether repair of a left-to-right shunt will be beneficial or, in a prospective cardiac transplant recipient, whether heart-lung transplantation is required. (See appropriate cards).
Lung biopsy ！ Pathological assessment of pulmonary artery hypertension requires lung biopsy. Historically, pathological examination has been used intraoperatively to look for evidence of irreversible pulmonary artery pathology. At present, right heart catheterization assessment of pulmonary vascular resistance and the vasodilator response are usually adequate to guide therapeutic decisions .
Other studies ！ Intravascular ultrasound may provide similar information without a lung biopsy. In a small study of patients with PAH from a variety of causes, autopsy comparison of histologic examination and intravascular ultrasound (IVUS) assessment of wall thickness and pathology showed a significant correlation between the two methods . However, a direct in vivo comparison to lung biopsy has not yet been performed.
Brain natriuretic peptide (BNP) is similar in its structure and activities to atrial natriuretic peptide but is produced primarily in the cardiac ventricles and therefore may be more sensitive and specific for the early detection of right ventricular dysfunction due to pulmonary hypertension. (See "Natriuretic hormones: Atrial peptides and ouabain-like hormone"). One study of 44 patients with right ventricular volume overload due to atrial septal defects or right ventricular pressure overload due to primary pulmonary hypertension or chronic thromboembolic disease found that plasma BNP concentrations correlated positively with mean pulmonary artery pressure, total pulmonary resistance, and right ventricular mass . Patients with right ventricular pressure overload had significantly higher plasma BNP levels than patients with right ventricular volume overload, suggesting that BNP measurements may assist in determining the etiology of pulmonary hypertension.
RECOMMENDATIONS ！ The history, physical examination, chest radiograph, and electrocardiogram may suggest the presence of PAH and right ventricular dysfunction, although the expected findings are frequently obscured by the underlying etiology.
• Two-dimensional transthoracic echocardiography with Doppler analysis can be used to confirm the diagnosis of PAH and to exclude possible cardiac disease. In most patients, the presence of PAH can be established by analysis of the tricuspid regurgitant jet. The addition of saline contrast and exercise increases the sensitivity of this test.
• In patients without primary cardiac disease, pulmonary function tests should be obtained, including blood gases and assessment of possible nocturnal desaturation. The findings can point toward COPD or interstitial lung disease, which can be evaluated further with CT scan and possible lung biopsy.
• Patients with relatively normal pulmonary function tests should undergo a perfusion lung scan and, if defects are present, pulmonary angiography.
• We recommend right heart catheterization if the presence of PAH is strongly suspected but noninvasive testing is not definitive. Right heart catheterization also permits assessment of the reversibility of pulmonary artery hypertension with vasodilators, and quantification of pulmonary vascular resistance. This information can be used to estimate the likelihood of success of potential medical and/or surgical intervention.
Palevsky, HI, Fishman, AP. Chronic cor pulmonale. Etiology and management. JAMA
2. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease. Ann Intern Med 1980; 93:391.
3. Stuckey, D. Cardiac pain associated with mitral stenosis and congenital heart disease. Br Heart J 1955; 17:397.
4. Morrison, DA, Klein, C, Welsh, C. Relief of right ventricular angina and increased exercise capacity with long term oxygen therapy. Chest 1991; 100:534.
5. Fishman, AP. Pulmonary hypertension and cor pulmonale. In: Pulmonary Disease, Fishman, AP (Ed), McGraw Hill, New York, 1989.
6. Weitzenblum, E, Apprill, M, Oswald, M, et al. Pulmonary hemodynamics in patients with chronic obstructive pulmonary disease before and during an episode of peripheral edema. Chest 1994; 105:1377.
7. Campbell, EJM, Short, DS. The cause of oedema in cor pulmonale. Lancet 1960; 1:1184.
8. Richens, JM, Howard, P. Oedema in cor pulmonale. Clin Sci 1982; 62:255.
9. Farber, MO, Roberts, LR, Weinberger, MH, et al. Abnormalities of sodium and H2O handling in chronic obstructive lung disease. Arch Intern Med 1982; 142:1326.
10. Schafer, JA. Mechanism coupling the absorption of solutes and water in the proximal nephron. Kidney Int 1984; 25:708.
11. Reihman, DH, Farber, MO, Weinberger, MH, et al. Effect of hypoxemia on sodium and water excretion in chronic obstructive lung disease. Am J Med 1985; 78:87.
12. Klinger, JR, Hill, NS. Right ventricular dysfunction in chronic obstructive pulmonary disease. Chest 1991; 99:715.
13. Mikami, T, Kudo, T, Sakurai, N, et al. Mechanisms for development of functional tricuspid regurgitation determined by pulsed Doppler and two dimensional echocardiography. Am J Cardiol 1984; 53:160.
14. Yock, PG, Popp, RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984; 70:657.
15. Otto, C. Textbook of clinical echocardiography. In: Pearlman, S (Ed), Saunders, Philadelphia, 1995.
16. Berger, M, Haimowitz, A, Van Tosh, A, et al. Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J Am Coll Cardiol 1985; 6:359.
17. Himelman, RB, Struve, SN, Brown, JK, et al. Improved recognition of cor pulmonale in patients with severe chronic obstructive pulmonary disease. Am J Med 1988; 84:891.
18. Himelman, RB, Stulbarg, M, Kircher, B et al. Noninvasive evaluation of pulmonary artery pressure during exercise by saline enhanced Doppler echocardiography in chronic pulmonary disease. Circulation 1989; 79:863.
19. Lunn, RJ. Inhaled nitric oxide therapy. Mayo Clin Proc 1995; 70:247.
20. Adatia, I, Perry, S, Landzberg, M, et al. Inhaled nitric oxide and hemodynamic evaluation of patients with pulmonary hypertension before transplantation. J Am Coll Cardiol 1995; 25:1656.
21. Alpert, JS, Dalen, JE. Pulmonary vascular disease in adults with congenital heart disease. In: Cardiology, Parmley, WW, Chatterjee, K (Eds), JB Lippincott, Philadelphia 1987.
22. Ishii, M, Kato, H, Kawano, T, et al. Evaluation of pulmonary artery histopathologic findings in congenital heart disease: An in vitro study using intravascular ultrasound imaging. J Am Coll Cardiol 1995; 26:272.
23. Nagaya, N, Nishikimi, T, Okano, Y, et al. Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension. J Am Coll Cardiol 1998; 31:202.