|IMAGING IN PVD
|Year : 2009 | Volume
| Issue : 3 | Page : 180-185
Imaging the right ventricle in pulmonary hypertension
Kevin G Blyth, Andrew J Peacock
Scottish Pulmonary Vascular Unit, Regional Heart and Lung Centre, Western Infirmary, Glasgow, United Kingdom
|Date of Web Publication||27-Jul-2009|
Andrew J Peacock
Director, Scottish Pulmonary Vascular Unit, Level 1, Regional Heart and Lung Centre, Golden Jubilee National Hospital, Beardmore St, Glasgow, G81 4HX
| Abstract|| |
Although the prognosis for patients with Pulmonary Hypertension (PH) has improved over recent decades, it is still difficult to predict clinical outcome in individual patients. In all forms of the disease, right ventricular (RV) function remains the most important determinant of survival and the difficulties encountered in predicting prognosis in individuals reflects the heterogeneous response of the RV. Our understanding of the mechanisms that underpin RV failure or adaptation in response to PH has greatly improved over recent years, as has our ability to accurately identify prognostically significant RV dysfunction in patients with PH. These advances have been driven by significant improvements in established RV imaging tools, such as 2-D echocardiography, and by the development of entirely new techniques, such as 3-D echocardiography, tissue Doppler imaging and cardiovascular magnetic resonance imaging. The purpose of this article is to review these techniques and to summarize these recent advances.
|How to cite this article:|
Blyth KG, Peacock AJ. Imaging the right ventricle in pulmonary hypertension. PVRI Review 2009;1:180-5
| Introduction|| |
In all forms of pulmonary hypertension (PH), right ventricular (RV) function remains the principal hemodynamic determinant of survival. ,,,,, Although the prognosis of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) has improved with the development of more effective medical and surgical treatments, our understanding of the factors that determine how the RV responds to PH remains incomplete. For example, it is not clear why some patients are able to adapt and tolerate very high pulmonary artery pressures (PAP), while others with similar, or even less significant, pressures develop rapidly progressive RV failure and die in a low cardiac output state.
In recent years, researchers have utilized new or improved imaging technologies to more accurately describe RV function in PH patients and investigate the adaptive responses that occur in some patients. These techniques, which have been used in cross-sectional studies and in the longitudinal monitoring of response to PH therapies, are the subject of this review.
| The Normal RV|| |
The term 'right ventricle' is really a misnomer. The 'rightness' of the RV reflects the natural orientation of the explanted heart as it lies on the dissection table. In the normally connected in vivo human heart, the RV is an anterior structure lying almost in the midline. The shape of the RV is complex and has been likened to a truncated ellipsoid pyramid, draped around the cylindrical left ventricle (LV) [Figure 1]. Under normal conditions, the RV is thin-walled but heavily trabeculated. It is a low-pressure volume pump, working against a resting pulmonary vascular resistance (PVR), which is only one-fifteenth of normal systemic vascular resistance. The thin-wall, anterior, midline orientation, and complex geometry of the RV pose particular challenges for all imaging methods. The techniques that have been used with considerable success in PH patients are echocardiography (including 3-dimensional echocardiography and Tissue Doppler Imaging), cardiac magnetic resonance (CMR) imaging and cardiac computed tomography (CT) imaging.
|Figure 1: Surface anatomy of the human RV as it lies in the thoracic cavity. [Reproduced from the 20th edition of Gray’s Anatomy of the Human Body, originally published in 1918]|
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| Echocardiography|| |
2-dimensional (2-D) echocardiography is cheap, portable and convenient. It is most commonly used for the detection of suspected PH in a symptomatic individual but also has a role in establishing an underlying cause (e.g. left ventricular dysfunction, intracardiac shunt). In patients with an established diagnosis, 2-D echocardiography is commonly used to assess and monitor biventricular function, valvular function, IVC dimensions and pericardial effusion [Figure 2].
|Figure 2: Apical four-chamber two-dimensional echocardiography image showing enlarged right-sided chambers with a small left ventricle (RV: right ventricle, LV: left ventricle, RA: right atrium, and LA: left atrium)|
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PAP can be derived non-invasively using a simplified version of Bernoulli's equation to convert the driving pressure gradient measured across the tricuspid valve by 2-D Doppler into systolic PAP. In the absence of pulmonary valve stenosis, systolic PAP = 4 ´ (peak tricuspid valve jet velocity)  + estimated right atrial pressure (RAP);  [Figure 3]. RAP can be estimated by various methods including the Inferior Vena Cava (IVC) collapsibility index and the height of the jugular venous pressure on clinical examination. Tight correlation between these measurements and invasive PAP has been demonstrated in earlier studies (r = 0.89-0.97). ,,, As a result, Doppler echocardiography has been established as the non-invasive screening investigation of choice in suspected cases of PH.
|Figure 3: Doppler estimation of systolic pulmonary artery pressure using two-dimensional echocardiography. The peak tricuspid regurgitation (TR) velocity of 4.80 m/s equates to a systolic PAP of 92 mmHg (plus right atrial pressure), indicating severe pulmonary hypertension|
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However, a number of earlier studies report relatively high standard errors of estimation (between 4.9 and 8 mmHg), , thus making the accurate definition of systolic PAP in individuals less reliable. A recent study has supported these concerns, demonstrating wide Bland-Altman limits of agreements around Doppler estimates of systolic PA pressure (+38.8 to -40.0 mmHg) in PH patients and inaccurate results (≥10 mmHg discordance with invasive measurements) in almost half the patients studied.  Furthermore, the normal range of systolic PAP varies with age, sex and body mass index, and normal systolic PAP may be 40 mmHg or more in some older or obese subjects. Doppler measurements are also operator dependent and may be particularly difficult to perform in obese patients and those with lung hyperinflation, e.g., in one cohort of COPD patients, only 25% of examinations were successful.  Intravenous contrast administration during 2-D echocardiography can enhance faint Doppler tricuspid flow signals and assist in non-invasive pressure estimation. Contrast echocardiography can also be used to detect intra-cardiac shunts and improve endocardial border delineation in patients with sub-optimal acoustic windows.
2-D echocardiography is also commonly used to assess RV function in PH patients. However, this approach is compromised by the often flawed assumptions regarding RV geometry which relies upon 2-D measurements to generate three-dimensional RV volumes (and indirect RV ejection fraction (RVEF)). These assumptions become increasingly inaccurate as the diseased RV dilates, , thereby making it an imprecise method of measuring RV function in PH patients with RV failure. Indirect variables such as the Tei index, which are less reliant on these assumptions, have been shown to correlate closely with RV systolic function in PH patents.  However, these values are complicated to define and are reliant upon an experienced operator. A recent study has shown that tricuspid annular plane systolic excursion (TAPSE), which is easier to acquire than the Tei index, relates closely to RV systolic function and survival in PH patients  and may prove to be more useful in clinical practice.
Recently, 2-D echocardiography has been successfully used to identify the positive treatment effects in randomized controlled trials of PH therapies, including improvements in RV and septal morphology and a reduction of maximal TR jet velocity in response to intravenous epoprostenol  and improvements in RV morphology and function in response to Bosentan. 
3-D echocardiography eliminates the need for geometric assumptions and provides direct and more accurate measurements of RV volumes and systolic function than 2-D measurements. , However, the clinical application of these techniques has been limited to date because of the need for time-consuming post-imaging analysis. Recent software improvements that allow real-time 3-D imaging and analysis may overcome these problems and allow 3-D echocardiography to enter routine clinical practice. 
Tissue Doppler imaging
Pulsed or color tissue Doppler imaging (TDI) allows the measurement of global and regional myocardial velocity and strain. Measurements are most commonly made of the RV free wall or tricuspid valve annulus. These values have been shown to correlate with RV systolic function  and invasive pulmonary hemodynamics  in PH patients and survival in patients with symptomatic heart failure.  TDI is available on most modern echocardiography machines, and the analyses are often easier and less time-consuming than equivalent 2-D studies.  TDI may prove a useful means of detecting early RV dysfunction in PH patients, allowing earlier risk stratification and better targeting of therapies.
| Cardiovascular Magnetic Resonance Imaging|| |
Cardiovascular magnetic resonance (CMR) imaging is an attractive modality for studying the complex geometry of the RV since geometric assumptions are not required. Direct volumetric measurements can be made in any plane and at almost any angle, and image quality is not affected by other acoustic windows, body habitus or coexisting lung disease. Furthermore, CMR imaging is fundamentally safe and no short- or long-term ill effects have been reported at the field strengths in current clinical use (up to 3 Tesla).
Potential drawbacks to the technique include its complexity and the need for expensive equipment, expertise and adequate time for image analysis. Claustrophobia is often quoted problem, but is relatively uncommon (occurring in approximately 2% of patients ) and can often be overcome by the use of mild sedation. Clearer contra-indications include ferrous metal implants, such as pacemakers and joint prostheses and gadolinium contrast reactions, particularly in patients with chronic renal impairment. 
Rapidly acquired gradient echo CMR sequences allow the detailed description of the complicated RV cavity by a series of short-axis cine images extending from the atrioventricular valve plane to the cardiac apex [Figure 4]. Planimetry of the end-diastolic and end-systolic images at each slice position, integration with slice thickness and summation of the resulting volumes using Simpson's rule produces highly accurate and reproducible measurements of RV volume, , ejection fraction , and mass.  RV mass index (RV/LV mass) has been shown to correlate with invasive mean PAP in humans with PH. , CMR imaging also allows detailed description of paradoxical (leftward) septal bowing in PH patients. In a recent study, Roeleveld et al., demonstrated that quantitative description of this leftward septal curvature (defined as the reciprocal of the radius) produced values that were directly proportional to systolic PAP (r = 0.77, P < 0.001). 
|Figure 4: A short-axis cardiovascular magnetic resonance imaging cine image (TrueFISP by Siemens) acquired at a mid-ventricular slice position in early diastole in a patient with PH. The right ventricle (RV) is dilated, hypertrophied and trabeculated and the interventricular septum (blue arrow) is displaced towards the left ventricle (LV) during this phase of the cardiac cycle|
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Velocity encoded (or phase-contrast) flow mapping is also possible using CMR imaging. This technique utilizes the phase difference acquired by tissue (blood) protons as they move through a strong magnetic field to generate blood velocity, flow and stroke volume data. Flow mapping is a more precise means of measuring RV stroke volume in PH patients as severe TR can lead to over-estimation of this value by planimetry. , Flow mapping can also be used to measure pulmonary artery distensibility, which is a reflection of the elastic properties of the proximal pulmonary vasculature. Previous studies using this technique have found highly heterogeneous velocity profiles, a large volume of retrograde flow, and decreased distensibility of the main pulmonary artery in patients with PH. , Flow mapping can also be used to accurately quantify intra-cardiac shunts by comparing pulmonary and systemic flow measurements in the great vessels. Trans-mitral and -tricuspid flow profiles can also be analysed, providing useful information on the filling characteristics of the left and right ventricles, respectively.
On the basis of these proven capabilities, CMR imaging is the currently accepted gold standard method of assessing RV structure and function in patients with PH and is currently being used as a treatment end-point in the EU-funded EURO-MR project.
Contrast enhanced-CMR imaging
Gadolinium is a paramagnetic CMR contrast agent with a high molecular weight. Clearance of gadolinium is delayed from necrotic or fibrotic tissue compartments, shortening the T1 time of the abnormal (myocardial) tissue and producing a bright MR signal on a T1-weighted gradient echo image (known as delayed contrast enhancement (DCE)). DCE is not biologically specific and has been detected in specific patterns in patients with myocardial infarction, fibrosis and myocarditis. ,,,, In PH patients, a unique pattern of DCE has been described within the IVS and RV insertion points due to fibrosis at these locations.  The extent of this fibrotic-DCE has been shown to relate inversely to RVEF and linearly with PAP and probably reflects high wall stress in these areas as a result of septal bowing during early diastole. ,,
Uniquely, CMR facilitates high-quality imaging of right and left ventricles simultaneously, providing an opportunity to study cardiac physiology and the interaction between the two ventricles under stress. Physical exercise within the confines of the magnet is technically difficult and leads to image degradation. However, some units have had success with this method using an MR compatible ergometer, demonstrating an impaired RV stroke volume response immediately after exercise in PH patients.  Dobutamine stress-CMR (ds-CMR) allows true stress measurements to be made and avoids potential errors related to exercise recovery. Ds-CMR has been successfully used to identify a reduced RV stroke volume and contractile response in minimally symptomatic patients with PH related to congenital heart disease ,, but has not been widely used in other patient groups.
| Cardiac Computed Tomography Scanning|| |
Recent improvements in computed tomography (CT) hardware and software have made cardiac CT scanning a more feasible option. Faster gantry rotation speeds, thin slice collimation and retrospective ECG-gating provide considerably improved temporal and spatial resolution, while multi-slice design implies that data acquisition times can be shortened to less than 20 s in most patients. Non-contrast scans are most commonly performed to assess calcified structures within the heart, such as coronary artery abnormalities. Since blood and soft tissue (e.g., myocardium) have similar CT attenuation, intravenous contrast administration is necessary to delineate the cardiac chambers, valves and great cardiac vessels; [Figure 5]. Thus, end-systolic and end-diastolic images can be produced and ventricular volumes and function analysed using similar planimetric methods to those described under CMR imaging. These values have been shown to be accurate and reproducible in PH patients. , However, cardiac CT imaging rarely has a major clinical role in most PH patients as echocardiography or CMR imaging can provide equivalent information without the need for contrast injection or radiation exposure. Nevertheless, cardiac CT is a useful alternative in selected situations, e.g., in patients with pacemakers or other devices that preclude CMR imaging.
|Figure 5: Contrast enhanced-computed tomography (CT) image obtained in a patient with severe pulmonary hypertension. The right-sided chambers are dilated and the right ventricle is hypertrophied (RV: right ventricle, LV: left ventricle, and RA: right atrium)|
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| Conclusions|| |
Recent years have seen the development of novel targeted anti-proliferative therapies for the treatment of PAH and continuing improvement in the surgical techniques used to treat proximal CTEPH. As a direct result of this progress, survival rates of patients with all forms of PH have greatly improved. However, RV failure remains inevitable in many and these new therapeutic options present new challenges for PH physicians. Accurate RV imaging tools are essential aids in choosing the correct treatment for the correct patient at the correct time and in identifying treatment successes and failures. Improved echocardiographic techniques (including TAPSE, 3-D echocardiography and TDI), CMR imaging and cardiac CT imaging offer great potential in this regard. Given its capacity for simultaneous anatomical and functional assessment, without the need for ionizing radiation, we anticipate that MR imaging will become an increasingly important investigation for patients with PH.
| Acknowledgments|| |
Dr. Lindsey McLure provided the images used in [Figure 2],[Figure 3] and [Figure 5].
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
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