Pulmonary Heart Disease (Cor Pulmonale)
Cor pulmonale is the enlargement of the right ventricle due to the increase in afterload that is caused by diseases of the thorax, lung and pulmonary circulation. It should be stressed that the presence of right ventricular failure is not essential for the diagnosis of this entity. Echocardiography is being considered as the ideal non-invasive test to assess individuals with suspected cor pulmonale. No patient risk, sufficient diagnostic accuracy, low cost, simplicity of use and ease of availability, meet the criteria of a useful and realistic key screening method. It directly reveals the primary and secondary anatomical and haemodynamic changes that occur during the adaptation of the heart to the pulmonary circulation haemodynamic overload while can also straightforwardly suggest alternative or even additional valvular, congenital or left-sided heart disease.
In brief, the screening echocardiographic findings in search of, are:
- right ventricular hypertrophy and/or dilatation due to adaptation of the right ventricle to pressure or volume overload state (video 1);
- increased tricuspid regurgitant velocity, a high prevalence finding linked to increased pulmonary artery pressures (fig 1);
- flattening and paradoxical movement of the interventricular septum (an also practical differential diagnostic “tool” between pressure and volume overloaded right ventricle) (video 2);
- dilated main pulmonary artery (video 3);
- mid- or early systolic closure of the pulmonic valve (video 4);
- right ventricular systolic dysfunction, a finding that is influenced by either the inotropic state or the loading conditions of the right ventricle. Hypokinesis of the free wall could be the first warning sign of the right ventricular failure (video 1).
Acute Cor Pulmonale
In the setting of acute pulmonary hypertension state, the right heart meets an abrupt increase in afterload without having the time to compensate as in the chronic pulmonary hypertension state. The role of echocardiography in the diagnosis and follow-up of these patients surprisingly has been poorly investigated. By reviewing the literature, earlier studies focused mostly on the diagnostic echocardiographic findings of confirmed pulmonary embolism cases or on the right heart changes after therapeutic manipulations in these patients . On the other hand, only small prospective studies defined the diagnostic accuracy of echocardiography in unselected patients with this condition . Interestingly, another report even suggested that the clinical utility of transthoracic echocardiography in the diagnostic work-up of pulmonary embolism is relatively limited .
Echocardiography assesses right ventricular size, function and pulmonary circulation pressures, parameters that are commonly affected by the acutely increased haemodynamic burden in pulmonary circulation.
Enlargement of a non-hypertrophied right ventricle is an anticipated physiologic response, but should also be regarded as a compensatory mechanism in the context of maintaining adequate perfusion of the pulmonary circulation by increased right ventricular preload (video 5). However, in case of acute pulmonary embolism, at least 25% obstruction of the pulmonary vascular bed is required for the echocardiographic findings to be noticeable and hence small emboli generally do not manifest any detectable changes in the echocardiographic examination. The right ventricle dilatation criterion was found to have low sensitivity even with exact measurements of right ventricular dimensions. Only in severe pulmonary embolism cases this criterion showed acceptable diagnostic accuracy.
|Video 5: Patient with acute pulmonary embolism after operation for pancreatic cancer. The right ventricle is dilated but not hypertrophied.|
The peak velocity of tricuspid regurgitation does not also seem to be a consistent diagnostic criterion since the right ventricular systolic pressure of a non-adapted right ventricle to acute hemodynamic burden does not increase remarkably even with massive pulmonary embolism cases. Peak tricuspid regurgitation velocity > 2.7 m/sec showed a sensitivity just above 50 % in an unselected patient population with suspected pulmonary embolism. Besides, this range of velocities is frequently encountered in daily clinical practice predominantly in patients having old age or hyperdynamic circulation conditions and as a consequence the specificity is questionable as well.
Another study recommended systematic diagnostic criteria for pulmonary embolism. The authors suggested the presence of any two echocardiographic findings of the following, a) a right ventricular end-diastolic diameter >27 mm, b) a tricuspid regurgitation velocity > 2.7 m/sec and c) right ventricular hypokinesis. This systematic approach showed a sensitivity of 56% and a specificity of 90% .
Transesophageal echocardiography showed a reasonable diagnostic accuracy only in identifying central pulmonary emboli and not for improving the diagnostic work up of unselected patients with suspected acute hypertension state. Thus, it is easily conceivable why it is not deemed the diagnostic method of choice and other imaging modalities are usually preferred in this setting (e.g. spiral computed tomography, ventilation-perfusion scan).
Chronic Cor Pulmonale
Although clinical assessment is crucial for the initial evaluation of patients with suspected chronic cor pulmonale, echocardiography gained its unique role in everyday clinical practice by providing valuable information, first by contributing to the screening and unravelling of the diagnostic algorithm, followed by the prognostic staging and finally the follow-up of these patients.
Echocardiography portends meaningful information on the adaptive mechanisms by which the right heart responds to the slow and augmented haemodynamic load invoked by several conditions (left heart, haemodynamically significant congenital, thoracic cavity, pulmonary parenchymal and pulmonary vasculature diseases). The differentiation between these variable groups of pathologies that finally conduct right chambers to the characteristic and persistent changes of pulmonary hypertension is a diagnostic challenge since different aetiologies account for different therapeutic strategies.
This section will not discuss the echocardiographic findings of the numerous types of left heart or congenital cardiac abnormalities but will rather focus on the chronic pulmonary hypertension state when this results from distinctive diseases of the lung, thorax or pulmonary circulation (chronic Cor Pulmonale).
In chronic Cor Pulmonale the major echocardiographic findings are the following:
- elevated pulmonary artery pressures,
- right ventricular hypertrophy, dilatation and systolic dysfunction,
- flattening and paradoxical movement of the interventricular septum and
- left ventricular diastolic dysfunction.
Elevated pulmonary artery pressures
In clinical practice the main echocardiographic measurement is the assessment of pulmonary artery systolic pressure. This parameter is generally useful for either screening or stratification of severity of chronic Cor Pulmonale state. In some groups of patients the pulmonary artery systolic pressure at presentation is mildly to moderately increased (e.g. chronic lung disease), while others present usually with severely increased pulmonary pressures (e.g. idiopathic pulmonary arterial hypertension). In the absence of right ventricular outflow or pulmonary valve stenosis pulmonary artery systolic pressure can be reliably deduced by summing the right ventricular-to-right atrial pressure gradient obtained via the peak tricuspid regurgitation velocity with the use of modified Bernouli equation, (gradient = 4Vmax, where Vmax is the maximal velocity of tricuspid regurgitation jet) and the mean atrial pressure as assessed by either echocardiographic or non-echocardiographic methods (inferior vena cava visualization, jugular venous pressure, central venous pressure) (pulmonary artery systolic pressure = gradient + mean right atrial pressure) (Table 1).
Table 1 Non invasive assessment of pulmonary arterial haemodynamics
|RVSP (PASP)||4 (VTR)2 + RAP|
|PAEDP||4 (VPR-ED)2 + RAP|
|mPAP|| 4 (V PR-PD)2 + RAP
79 – (0.45 x RVACT)
90 – (0.62 x RVACT)
log10 mPAP = 0.0068 (RVACT) + 2.1
|Pulmonary Arterial Resistances (Woods units)||10 (VTR / VTIRVOT ) + 0.16|
RVSP, right ventricular systolic pressure (mmHg); PASP, pulmonary artery systolic pressure (mmHg); VTR, peak tricuspid regurgitation velocity (m/s); RAP, mean right atrial pressure; PAEDP, pulmonary artery end diastolic pressure (mmHg); VPR-ED, end-diastolic velocity of pulmonary regurgitation signal; mPAP, mean pulmonary artery pressure (mmHg); VPR-PD, peak pulmonary regurgitant velocity in early diastole; RVACT, right ventricular acceleration time (ms); VTI, velocity time integral;, RVOT, Right ventricular outflow tract
The pulmonary artery diastolic pressure is also approximated by measuring regurgitant flow across the pulmonary valve using the same method. Considering that patients with chronic pulmonary hypertension typically have both tricuspid and pulmonary regurgitation it is easily conceivable why these measurements are of paramount importance for assessing the pulmonary circulation pressures.
Systolic and diastolic pulmonary artery pressures outline the pulse pressure of the pulmonary artery. Interestingly, one study revealed an association between the estimated pulsatility of the pulmonary artery with Doppler echocardiography and specific Cor Pulmonale conditions. In particular, it was demonstrated that chronic thromboembolic disease could be differentiated from the idiopathic pulmonary arterial hypertension on the basis of normalized PA pulse pressure.
Another report showed that the ratio of peak tricuspid regurgitant velocity to the right ventricular outflow tract velocity-time integral (peak VTR/VTIRVOT) provides a clinically reliable non-invasive assessment of pulmonary vascular resistance . However, the results of this study should be interpreted with caution because of essential limitations of the study protocol (exclusion of patients with more than moderate tricuspid regurgitation severity, relative unreliability of tricuspid regurgitation velocity only for the assessment of right ventricular pressure).
Right ventricular hypertrophy, dilatation and systolic dysfunction
Adaptation of the chronic overloaded right ventricle is accomplished principally by wall hypertrophy and secondly by chamber enlargement. A progressive volume overload due to further right ventricular dilatation and functional tricuspid valve insufficiency usually ensues. Significant tricuspid regurgitation is a finding that heralds the final stage of the disease since the additional increased volume overload state accelerates the progression to right ventricular failure.
For the evaluation of the right ventricle, accuracy and reproducibility are factors that should be taken into consideration. Earlier studies in patients with pulmonary disease, showed a great variation regarding the reliability of measurements, basically due to lack of standardization. Once those right heart measurements have been established  good reproducibility has been achieved and used in different clinical settings.
Two-dimensional imaging evaluates the dimensions, shape and thickness of the right ventricle using several tomographic planes. A useful parameter for the assessment of the degree of right ventricular dilatation is the measurement of its end-diastolic diameter at the level of the tricuspid chordae from the parasternal short axis or the four-chamber projection (fig 2).
Right ventricular areas are commonly used measures for assessing the right ventricular dimensions and function. The right ventricular end-diastolic and end-systolic cavity areas are conventionally determined by tracing the endocardial borders in the apical 4-chamber view. Moreover, both are useful parameters, integrated in several area-length mathematical formulas for volume calculations. Although these formulas have been used some times with great enthusiasm, their geometric model-based approach is generally accepted with scepticism.
Automatic endocardial border detection correlates well with the angiographic evaluation of the right ventricle. However, the reliability of this method for volumes’ evaluation is also questioned, due to the already mentioned limited application of geometric assumptions in right ventricle. The use of contrast agents improves accuracy.
The standard measurements of right ventricular volumes and ejection fraction are difficult and sometimes impossible to perform, due to the complex geometry and the increased RV trabeculation. Although three-dimensional echocardiography is capable of more accurate estimation of volumes, overriding the limitation of the geometric models, it cannot avoid neither the necessary planimetry of the endocardial borders nor the time consuming off-line analysis. Nevertheless, in the era of new commercially available three-dimensional systems and workstations for later analysis, an accurate measurement of both right ventricular size and function has now been achieved with acceptable reproducibility . The advent of real time three dimensional imaging, enabled a shorter examination time while promises to revolutionize cardiac imaging (video 6). A study with real time three dimensional echocardiography in animal model, demonstrated that right ventricular stroke volume could be measured sufficiently in chronic right ventricular volume overload state.
Identification of right ventricular systolic dysfunction has an important impact on prognosis in a variety of chronic pulmonary hypertension conditions . The term ‘systolic dysfunction’ is generally preferred to the term ‘impaired contractility’, since right ventricular systolic function can be affected by changes not only attributed to inotropic state but to preload and afterload conditions as well.
Deformation of the interventricular septum
The interventricular septum, an anatomical structure that separates the right and left ventricular chambers, can become a practical “tool” for differentiating between pressure and volume overload physiologies in different chronic pulmonary hypertension conditions. During cardiac cycle the motion of the interventricular septum indicates the developing pressure difference between the two ventricles. In volume overload states (e.g. significant atrial septal defect) flattening occurs typically only in diastole, since the rising left ventricular pressure during systole is higher than the right ventricular one (video 7). On the contrary, in pressure overload states (e.g. idiopathic pulmonary arterial hypertension) the right ventricular pressure is generally high enough during the whole of the cardiac cycle and thus flattening exists in both systole and diastole (video 2).
Diastolic dysfunction of the left ventricle
Although Cor Pulmonale principally involves the right heart, left ventricular diastolic dysfunction is a condition that almost always coexists. The impaired transmitral diastolic filling is due essentially to the interdependence of both ventricles, the marked abnormal geometrical configuration of the left ventricle, the large decrease of its preload and some degree of left ventricular interstitial oedema which increases its wall stiffness as well. The severity of left ventricular diastolic dysfunction is closely related to the severity of pulmonary hypertension.
The remarkable progress of treating patients with chronic pulmonary hypertension that has occurred with either the use of novel drugs (e.g. prostacyclin and its analogues, sildenafil, endothelin receptor antagonists) or with technical advances in pulmonary thromboendarterectomy, has reduced mortality but as anticipated led to an increased morbidity which requires serial assessment of the applied therapy with the use of clinical and imaging techniques.
Right heart catheterisation and selective pulmonary angiography is characterized by a significant risk for adverse events and hence, except from baseline measurements, it is not an ideal test for follow-up. Helical computed tomography is only required as an adjunctive imaging technique to pulmonary angiography for the differential diagnosis and localization of chronic thromboembolic disease. Cardiac magnetic resonance imaging is a method that provides useful information for the complex right ventricular architecture, volume, mass and function. However, is time consuming, expensive and not available at the clinical ward.
Echocardiography has significant advantages over the other imaging modalities and could be ideally suited to follow up individual patients with known pulmonary hypertension. However, this issue could be regarded, as another ‘terra incognita’ since was never systematically described in scientific papers or textbooks.
Although several echocardiographic parameters have been utilised for the evaluation of the severity of these diseases, none is sufficiently robust on its own, capable to assess with accuracy in a simple, quick and reproducible way the progress of the disease.
Two and three dimensional parameters
The inherent problems of two dimensional echocardiography measuring the right ventricular dimensions, volume and systolic function have been described in a previous section. As a general conclusion, it seems that these measurements even crucial for screening do not have acceptable reproducibility for assessing serial changes attributed to either the progress of the disease or therapeutic manipulations. Measurement of the inferior vena cava diameter and its variation during the respiratory cycle (video 8) is important for the indirect evaluation of right atrial pressure and could be of value since central venous pressure is itself an independent prognostic factor for survival (Table 2).
Table 2 Non invasive assessment of central venous pressure
|IVC size (mm)||Respiratory variation||Estimated mean RAP (mmHg)|
|15-25 mm||>50% decrease||5-10|
|>25 mm||<50% decrease||10-15|
|>25 mm and dilated hepatic veins||No change||>15|
IVC, inferior vena cava; RAP, mean right atrial pressure
Reproducibility however is uncertain since the reference point for the measurement of the diameter and precise acoustic window, are ill defined.
|Video 8: Patient with Systemic lupus erythematosus and pulmonary arterial hypertension. A pacing wire is an absolute contraindication for this patient to perform MRI. Echocardiography is the method of choice for the diagnosis and follow up of this patient.|
Presence of pericardial effusion and the size of the right atrium are also two prognostic and potential follow-up factors in patients with pulmonary arterial hypertension. Nevertheless, pericardial effusion is rather uncommon and can only be assessed semiquantitatively (fig 3). In contrast, right atrial size measurement is more accurate and reproducible. Right atrial enlargement is a manifestation of high right atrial pressure and may be viewed as an indicator of right ventricular decompensation (Table 3).
Table 3 Right atrial volume measurements
|Single plane area-length method||Volume = 0.85 A2/L|
|Single plane diameter-length method||Volume = (πD2L)/6|
|Method of discs||Volume = π/4∑αi(L/n)|
A, area of right atrium; L, longitudinal dimension of right atrium; D, transverse dimension of right atrium; αi, area of disc; n, number of equal height discs.
Finally, measurement of left ventricular dimensions as a prognostic or follow-up factor may also be important. Right-sided volume or pressure overload can alter left ventricular systolic and diastolic function and this may have unpredictable clinical consequences between individuals even with the same degree of severity of right heart disease. Although left ventricle is displaced due to the clockwise rotation of the heart, measurement of the end-diastolic diameter is accurate and reproducible as well. Eccentricity index appears a reproducible measurement with an established clinical value for the evaluation of the severity of the pressure overload of the right ventricle, due to the displacement of the interventricular septum. It is calculated from the parasternal short axis projections as the ratio of the minor axis of the left ventricle parallel to the septum at the level of the chordae, divided to minor-axis perpendicular to and bisecting the septum at the same section (fig 4). Intravenous prostacyclin infusion of 12 weeks duration was able to improve significantly this index’ values .
Three dimensional echocardiography is a novel modality that might represent a justified application of cardiac imaging in the context of follow up of these patients (video 6). The assessment of right ventricular volume and function has nowadays good image quality while shows significantly better agreement and lower intra- and interobserver variability than two dimensional echocardiography. Speckle tracking echocardiography is an also novel modality that can reliably assess the regional and overall right ventricular deformation in several directions (i.e. longitudinal, radial and circumferential). This new technique is accurate enough to detect early subclinical right ventricular myocardial dysfunction in patients with systemic sclerosis and normal pulmonary pressures.
|Fig 3: Small pericardial effusion (arrow) in a patient with severe pulmonary hypertension and right ventricular failure||Fig 4: eccentricity index|
From Doppler parameters, peak tricuspid regurgitation velocity as already mentioned is doubtless a robust measurement for screening suspected pulmonary hypertension patients. When present, it can be easily measured with high reproducibility in nearly all cases. However, the significance of this parameter as far as the follow-up of these patients is uncertain.
In one study, Hinderliter et al noted that peak tricuspid regurgitation velocity was reduced in patients who received prostacyclin intravenously when compared to the control group. However, these differences before and after treatment seemed to be particularly small and certainly within the limits of the repeated measurements error, although this was not discussed by the authors.
Small differences of the peak tricuspid regurgitation velocity may occur due to the fall of the right ventricular systolic pressure. However, when pressure reduction occurs in parallel to a drop of right atrial pressure, this fall may lead to an unchanged pressure gradient overall between the two chambers, despite the presence of an obvious improvement of the symptoms and the functional stage of the patients. Therefore, lack of maximum tricuspid regurgitation velocity changes should be evaluated with caution when evaluating the progress of such patients.
Tricuspid regurgitation severity is an independent prognostic factor in patients with idiopathic pulmonary hypertension. However, due the substantial error of repeated measurements it cannot be considered as a robust parameter for follow-up (video 9 and 10). Tricuspid regurgitation may be under or overestimated due to the variable colour-Doppler gain adjustments or the variable size and compliance of the right atrium. The tricuspid regurgitation area over 30 cm2 as well as the ratio of the regurgitation area to the area of the right atrium >34%, had sensitivity for the detection of severe tricuspid regurgitation of 66% and 76% respectively.
|Video 9: Patient with HIV induced pulmonary arterial hypertension on admission. The tricuspid regurgitation is severe.||Video 10: Patient with HIV induced pulmonary arterial hypertension after 2 year treatment with Bosentan. A dramatic improvement in tricuspid regurgitation severity is evident.|
Pulmonary artery flow acceleration time is another hemodynamic parameter, which has been related to the mean pressure of the pulmonary artery. However, the short duration of acceleration time and its potential variation with a relatively small movement of the cursor during the measurement results to poor reproducibility.
Measurement of the regurgitant flow across the pulmonary valve is useful for the evaluation of the right ventricular diastolic pressures. Along with tricuspid regurgitation, it is a useful parameter for estimation of the pulse pressure of the pulmonary artery. The difference of the pulmonary artery pulse pressure has been proposed as a method of differential diagnosis between pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.
Doppler estimation of the trans-tricuspid diastolic velocity is based on the same pathophysiologic principles as the trans-mitral velocity. However, it requires an average number of at least 5 consecutive cardiac cycles due to the influence of respiration on pressure gradient through the tricuspid valve. Essential measurements are the peak velocity of E and A waves and the deceleration time of the E wave. In most cases, the E/A ratio is < 1 due to the increased RV hypertrophy and reduced compliance. In an advanced stage with ensuing systolic right ventricular failure οr with severe tricuspid regurgitation, diastolic dysfunction becomes progressively pseudonormalized, with a reversed E/A ratio (>1). It has to be emphasized that tricuspid flow pattern is strongly influenced by loading conditions of the right ventricle. Different patterns may be seen hours to days apart in the same patient, depending on the preload or afterload conditions.
Tissue Doppler echocardiography is another modality to evaluate right ventricular function. Assessment of tricuspid annular velocity is a simple and quick method with good reproducibility. Systolic velocity < 11.5 cm/sec can identify the presence of right ventricular dysfunction with a sensitivity and specificity of 90% and 85% respectively. Strain and strain rate did not show adequate reproducibility and thus have been practically abandoned clinically.
The Doppler-index of myocardial performance (Tei-index or myocardial performance index-MPI) is a parameter, which, although it was initially used for the evaluation of the overall left ventricular performance, it was also used for the evaluation of the right ventricular function. It is expressed by the formula [(isovolumic contraction time + isovolumic relaxation time) / right ventricular ejection time] (fig 5). It is relatively unaffected from heart rate, loading conditions or the presence and the severity of tricuspid regurgitation. In patients with idiopathic pulmonary hypertension, the index had a good correlation with symptoms, while also proved to be a good prognostic factor. The advantages of its use are good reproducibility, quick calculation, no need for use of geometric models and appliance even in the presence of a difficult acoustic window. The disadvantages are the lack of familiarity among physicians when compared to other more traditional indices (e.g. ejection fraction) and the overlapping which often occurs between the end of tricuspid regurgitation signal and the pulsed signal of the early diastolic filling (E) of the trans-tricuspid flow that challenges the accurate estimation of the isovolumic relaxation time. Nevertheless, Tei-index has become a robust prognostic factor with good reproducibility and makes it a useful measurement for patients’ follow-up.
Finally, another report showed that the ratio of peak tricuspid regurgitant velocity to the right ventricular outflow tract velocity-time integral (peakVTR/VTIRVOT) provides a clinically reliable non-invasive assessment of pulmonary vascular resistances. Yet, there is no clear evidence that this parameter could be used for follow up in the clinical setting of cor pulmonale.
- ↑ Come PC, Ducksoo K, Parker A, et al. Early reversal of right ventricular dysfunction in patients with acute pulmonary embolism after treatment with intravenous tissue plasminogen activator. J Am Coll Cardiol 1987; 10:971-978.
- ↑ Miniati M, Monti S, Pratali L, et al. Value of transthoracic echocardiographic in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients. Am J Med 2001; 110: 528-535.
- ↑ Bova C, Greco F, Misuraca G, et al. Diagnostic utility of echocardiography in patients with suspected pulmonary embolism. Am J Emerg Med 2003; 21:180-183.
- ↑ Miniati M, Monti S, Pratali L, et al. Value of transthoracic echocardiographic in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients. Am J Med 2001; 110: 528-535.
- ↑ Abbas A, Fortuin D, Schiller N, Appleton C, Moreno C, Lester S: A simple method for noninvasive estimation of pulmonary vascular resistance. J Am Coll Cardiol 2003, 41:1021–7.
- ↑ Foale RA, Nihoyannopoulos P, McKenna WJ, Kleinebenne A, Nadazdin A, Rowland E, et al: Echocardiographic measurement of the normal adult right ventricle. Br Heart J 1986, 56:33-44.
- ↑ Menzel T, Kramm T, Bruckner A, Mohr-Kahaly S, Mayer E, Meyer J: Quantitative assessment of right ventricular volumes in severe chronic thromboembolic pulmonary hypertension using transthoracic three-dimensional echocardiography: changes due to pulmonary thromboendarterectomy. Eur J Echocardiography 2002, 3: 67-72.
- ↑ Burgess MI, Bright-Thomas RJ, Ray SG: Echocardiographic evaluation of right ventricular function. Eur J Echocardiography 2002, 3:252-262.
- ↑ 9.0 9.1 Hinderliter AL, Willis PW, Barst RJ, Rich S, Rubin LJ, Badesch DB, et al: Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Primary Pulmonary Hypertension Study Group. Circulation 1997, 95:1479-86.
- ↑ Wilkins M, Paul G, Strange J, Tunariu N, Gin-Sing W, Banya W, Westwood M, Stefanidis A, Ng L, Pennell D, Mohiaddin R, Nihoyannopoulos P, Gibbs JS. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) Study. Am J Respir Crit Care Med. 2005 Jun 1;171 (11):1292-7.
- Lang R, Bierig M, Devereux R, et al. Chamber quantification: EAE recommendations. J Am Soc Echocardiogr. 2005 Dec;18(12):1440-63. This document reviews the technical aspects on how to perform quantitative chamber measurements of morphology and function, which is a component of every complete echocardiographic examination. http://www.escardio.org/communities/EAE/publications/Documents/eae-lang-chamber-quantification.pdf
- Guidelines for the diagnosis and treatment of pulmonary hypertensionEuropean Heart Journal (2009) 30, 2493–2537 http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-PH-FT.pdf