RIGHT SIDE OF THE HEART: ASSESSMENT BY TRANSTHORACIC ECHOCARDIOGRAPHY

Echocardiographic evaluation of right heart has been a neglected area of Transthoracic studies. As technology improved, it has taken rapid strides, for structure and functional assessment. Right heart function has proven prognostic implications. Echocardiographic evaluation of the Right Heart spans from M-mode to 2 and 3 dimensional studies, Doppler (Pulsed wave, Continuous wave, color and tissue), and recent addition of Speckle Tracking. In this review, the definitions, echocardiographic methods, limitations and prognostic implications of the parameters used to assess Right heart structure and function by Trans-thoracic echocardiography (exclusive of 3D) have been detailed.


INTRODUCTION
Evaluation of Right heart by echocardiography has been relatively unattended due to:  The anatomy is very complex.  Difficult to image as it lies behind the breast bone.  RV wraps around LV, making the assessment of in-and outflow tracts in one view impossible and coarse trabeculations, make imaging and measurements difficult, Figure 1. 1

Figure 1: Right Ventricle (anatomical specimen, Cut section (A) to show the heavy trabeculae and wrapping around LV in a crescentic manner (B)
Assessment of different components of Right heart by echocardiography especially for diagnosis and prognosis would be detailed. The range of normal values for each parameter have been derived from authentic and validated guidelines provided by international agencies, i.e. American Society of Echocardiography/European Society of Cardiology 2 and British Society of Echocardiography. 3 This manuscript covering the above-mentioned aspects will be unique and helpful for echocardiographers, cardiologists and physicians in making clinical decisions.

An internet search of Pub-Med and Pakistan Heart
Journal was done with the key words, "Echocardiography", "Right Heart", "Pulmonary Hypertension", "Chamber quantification" and "Prognosis" which fetched 585 results. From these, 24 were found relevant for this manuscript for the extraction of data and textual facts.

Vena Cavae
Superior Vena Cava can be visualized from Suprasternal window in Short Axis (Coronal) view, as shown in Figure 2.

Figure 2: Superior Vena Cava from Supra-sternal View
The entry of inferior vena cava into RA is guarded by "Eustachian Valve", usually rudimentary but at times is quite big, confusing for a cardiac tumor, Figure 3.

Figure 3: Eustachian valve Rudimentary (usual) and very large (unusual)
IVC is examined from sub-costal window along the short and long axes and the caliber is measured in long axis 1-2 cm distal to its opening into RA, Figure  4.

Figure 4: IVC measurement from sub-costal Long Axis View
The size and collapsibility of IVC varying with respiration (> 20%) or with a sniff (caval index > 50%) help in the measurement of RA Pressure, Table 1.
Pellicori et al, in 693 patients with heart failure, found a correlation for adverse prognosis between IVC diameter and log NT-BNP, an indicator of heart failure (r= 0.55; p < 0.001). 4

Right Atrium
Comprising of body and appendage, it is evaluated in apical 4C view. The parameters are dimensions, area and volume. Dimensions are transverse and vertical, former is measured from the mid of interatrial septum to the lateral wall and later from mid of superior wall to the mid of Tricuspid annulus, Figure 5A. The area of Right Atrium is also measured in this view, Figure 5B. Right atrial volume is measured by Modified Single Plane Simpson's method, Figure 5C or by Area-Length method by the formula 0.85 x (RA 4C Area2 ÷ RA Length), Figure  5D. The values for various RA measurements are as shown in Table 2.
Ronald J. Raymond et al, reported in 41 patients, "in severe primary pulmonary hypertension, indexed right atrial area is a predictor of mortality, while pericardial effusion and indexed RAA of an adverse outcome (transplant or mortality) in multi-variant analysis". 5

Tricuspid Valve
This is the largest valve comprising of annulus, leaflets, chordae and papillary muscles. Tricuspid annulus is oriented nearly vertically at an angle of approximately 45 degrees from the Sagittal plane, saddle shaped with outline varying from triangular to ovoid. A nearly 40% dilatation of Tricuspid annulus results in significant regurgitation. Functional TR results more from dilatation of anterior and posterior portions with relative sparing of septal region. Full analysis of tricuspid valve by 2D echocardiography requires multiple views as shown in Table 3.   Tenting area is bounded by the Septal and Anterior leaflets along with TV annulus, Figure 8, whereas, Tethering Height is the distance from mid of Tricuspid Annulus to the meeting point of Tricuspid leaflets at end systole. Tethering distance > 0.76 cm or Tenting area > 1.63 cm 2 are indicators of postoperative recurrent TR". 6 Girish Dwivedi et al in 554 normal adults, more than 60 years of age measured these parameters as shown in Table 4. 7

Figure 8: Tenting Area of Tricuspid valve
Tricuspid valve is mainly affected either by stenosis or regurgitation.

Tricuspid Stenosis
For stenosis assessment, the TTE parameters are: 2D planimetry, pressure gradient assessment, mean and peak (by applying Bernouilli's equation), and valve area estimation (by pressure half time, and continuity equation).
In case of Tricuspid stenosis, 2D planimetry is not possible.
Pressure gradients across TV are assessed by CW Doppler. The time taken for the peak pressure to drop to half give pressure half time and dividing 190 by it will give the area.
By measuring the diameter of LVOT in PS long axis and VTIs of flows across LVOT (in apical 5C view) and Tricuspid valve (in apical 4C view), Figure 9 and applying the following equation, the area of a stenotic Tricuspid valve can be obtained. The parameters of severe Tricuspid stenosis are as shown in Table 5. 8

Tricuspid Regurgitation
Assessment of regurgitation severity for any valve is done mostly by qualitative, semi-quantitative and quantitative methods. 2D assessment of morphology of the leaflets is the beginning point. The parameters are: Vena-contracta width, regurgitant area, regurgitant area to recipient chamber's area ratio, regurgitant volume (estimated by continuity equation or PISA), and effective regurgitant orifice area (EROA). Vena contracta, the narrowest point of regurgitant flow, Figure 10 is easy to measure and is highly specific for regurgitation severity.
As regurgitant flow converges towards the valve orifice, iso-velocity concentric layers forming hemispherical shells are seen. Flow through the surface area of each shell is equal to the amount of blood passing through the orifice. As the velocity of shells increases, aliasing is noted on color doppler. From the radius of the first aliased hemi-sphere and the aliasing velocity (from color velocity bar), the regurgitant flow can be discerned by the formula: 9 Regurgitant Flow = 2πr 2 × Aliasing Velocity The regurgitation severity could be mild, moderate or severe as elaborated by the European Association of Cardiovascular Imaging in their recommendations" 10 Lately, two further grades have been added viz, massive and torrential as shown in Figure 11. 11

Right Ventricle
Eyeball comparison of LV and RV sizes can indicate RV enlargement (1).
RV function should be assessed by multiple parameters 12 with proven diagnostic and prognostic values.

Right Ventricle Dimensions
Three dimensions are taken in Apical 4C RV directed view as follows: Get a good quality apical 4C view, move the transducer laterally, focusing medially to make RV lie in the center but with LV apex remaining central at the top of the image. Lastly, rotate the transducer to get the maximum dimension at the base and along the long axis", 13 Figure 12.   RV outflow tract is measured at proximal and distal site, former in PLAX or PSAX view, whereas, later in PSAX view, just proximal to the pulmonic valve at end systole (Figure 15), Normal values are shown in Table 6. Increase in RV size is a marker of adverse prognosis in many conditions like chronic pulmonary disease, idiopathic pulmonary hypertension, acute pulmonary embolism, myocarditis and chronic heart failure.

Right Ventricle Functional Assessment
These parameters could be focal, Tricuspid Annular Plane Systolic Excursion (TAPSE) and S' velocity or global, which include RV Fractional Area change, Myocardial Performance Index and RV free wall strain assessment. The normal values have been tabulated in Table 7.

RV Tricuspid Annular Plane Systolic Excursion (TAPSE):
TAPSE is the distance moved by the lateral annulus of Tricuspid valve during systole. It is measured in A4C view by M-mode, Figure 16 and the main advantages are its easy obtainability and universal availability but, it is angle and volume dependent.

RV Fractional Area Change (RV FAC):
Area of Right ventricle is measured in A4C RV directed view at end diastole and end systole, Figure  17. It has proven value as a predictor of sudden death, heart failure and stroke after MI and Pulmonary Embolism.

RV Volumes and Ejection Fraction:
These parameters are not recommended by current guidelines.

RV S' Velocity:
Robust and highly reliable. It measures the velocity of RV myocardium in A4C view by TDI or Color-Coded Tissue Doppler. The sample volume is placed at the lateral tricuspid annulus or basal segment of RV free wall, Figure 18. Limitations and advantages are same as of TAPSE and is less loaddependent.

Figure 18: S' velocity measurement by Color coded tissue doppler and Tissue doppler.
Numerous studies have shown the prognostic value (for survival and morbidity) of S' velocity with variable cutoffs from 9 cm/s -10.8 cm/s. 16

RV Isovolumic Acceleration:
A relatively new parameter confined to Isovolumic contraction time. It is relatively less load-dependent and measured by Color-Coded Tissue Doppler like S' velocity. The initial spike during systole in TDI record is the Isovolumic time, Figure 19. Its height represents the maximum velocity and the time to reach it is the Acceleration time. IVA is obtained by the formula: cm/s 2

Figure 19: Isovolumic Acceleration Time measurement by Color coded Tissue Doppler imaging.
In their study of 413 subjects, Jerome Peyrou et al, found, "of the newer parameters, RV function assessment by IVA (≤ 1.8 cm/s2) had a sensitivity of 86% and specificity of 97% and is the best parameter in this regard, even surpassing basal 2D strain analysis". 17

RV Myocardial Performance Index (RMPI -TEI INDEX):
It assesses systolic as well as the diastolic function and is obtained by the equation:  It is load-dependent but doesn't pose a problem for acquisition and no assumption for geometry is needed. It can be obtained by Color-Coded DTI or PW Doppler. The former is better as all the variables of the equation can be obtained in the same view.
RIMP has proven its prognostic value in clinical trials in multiple clinical scenarios like Pulmonary Hypertension, LV dysfunction, acute RV myocardial infarction, chronic and acute pulmonary thromboemboli, after heart valve surgery and in congenital heart disease.

Right Ventricular Strain:
It detects myocardial dysfunction earlier than conventional echocardiography. For this, an RV focused view is obtained with a good Region of Interest encompassing the full thickness of the myocardium, Figure 21. Either a six segment approach, or a three segments approach is used, the latter being preferable. 2D strain of only the basal segment of RV indicates RV systolic function. Being angle plus load independent (relatively), and having good reproducibility with low inter and intra observer variability, it is emerging as a robust parameter for RV function assessment.
Focardi et al have demonstrated that RVLS has a strong correlation with CMR-derived RVEF than conventional echo methods. 18 The main limitations are: sinus rhythm (with HR 60-100 bpm) is mandatory, good acoustic image, requires a dedicated software, only longitudinal strain can be assessed currently and uniform universal standards are still lacking.
RVLS has shown prognostic value in various clinical scenarios like Acute MI, PAH, Heart failure (moderate), operated cases of TOF, heart transplant recipients and in ARVD.

Right Ventricular Diastolic Function
In apical 4C view with the sample volume of PW Doppler placed between the tips of Tricuspid leaflets, Figure 22, flow velocities are measured, either in held respiration or an average of 5 cycles taken.
Velocities of early flow (E-wave), late flow (A-wave), their ratio (E/A) and the deceleration time of E wave should be recorded. With the sample volume of Tissue Doppler placed at the lateral Tricuspid annulus, Isovolumic relaxation time (IVRT), E' velocity, A' velocity, E'/A' ratio and E/E' ratio are obtained.

Figure 22: Measurement of Diastolic Functional Parameters by Pulsed Wave Doppler (A) and Tissue Doppler (B).
Diastolic dysfunction has been graded as: Moderate---E/A is 0.8-2.1 and E/E' < 6 or dominant diastolic flow in the hepatic veins,  Severe---E/A > 2.1 and DT < 120 ms.
The normal ranges of diastolic parameters of Right ventricle are as shown in Table 8.
Noha H et al demonstrated that in hypertensive patients, RVDD accompanies LV diastolic dysfunction. The overall prevalence of RVDD was higher than that of RVSD, and the highest prevalence of the latter was recorded in subjects with elevated PASP and dilated left atrium. 19

Pulmonary Valve
Located most superiorly and anteriorly it is the most difficult to image. Imaged in RV outflow tract view, PS SAX, and sub-costal sagittal view. In any view, only two leaflets are visible. Pathological affliction results in stenosis or regurgitation.
2D echocardiography assesses morphology, and grading of stenosis severity 8 is done by estimation of Peak and mean gradients. Valve area is estimated by Continuity equation, Table 9.

Pulmonary Artery
Main Pulmonary artery is seen in PS LAX and SAX views whereas the later view shows branches clearly and their sizes can be measured from PS SAX or Suprasternal view, Figure 23. The normal ranges and the cut-offs for severity assessment are shown in Table 10.  Assessment of Pulmonary artery pressure is extremely important. It could be peak systolic, mean and end-diastolic. Pulmonary Vascular Resistance can also be derived from these parameters.
Pulmonary artery hypertension, traditionally defined as mPAP ≥ 25 mmHg, was revised at the Sixth World Symposium on PAH in 2018 and the thresholds suggested were as shown in Table 11. 21  If the velocity of TR jet > 3.4 m/s, diagnosis of PAH is highly likely, whereas if it is < 2.8 m/s, PAH is unlikely and for values in between, other parameters should be taken into account.
Mean Pulmonary Artery Pressure, can be measured by:

Early diastolic flow velocity of a Pulmonary
Regurgitation jet as TR jet velocity is used for PASP estimation and, with addition of mean RA pressure, Figure 25.
2. Pulmonary Acceleration is measured from the inception of PA flow till its peak by PWD. Two formulae have been proposed for the estimation of mean PAP:  3. From mean RV-RA gradient with addition of RA pressure.
4. Can also be calculated from peak PAP: 23 Mean PA pressure = 0.6 (peak systolic PAP) + 1.95 Pulmonary Artery Diastolic pressure can be estimated from end pulmonary regurgitation flow by modified Bernoulli equation and adding to it mean Right Atrial pressure, Figure 25.
Other parameters like TVI of PA systolic flow, sizes of RA, RV and Pulmonary arteries should be taken into account when labelling for PAH.
Hepatic vein flow helps in diagnosing PAH. By PW Doppler, Hepatic venous flow is recorded, which, shows two prominent negative waves, one each in diastole and systole, later bigger than former. Two smaller waves are also recorded, as shown in Figure  26.

Figure 26: Hepatic Vein flow from Sub-costal window
An attenuation in the size of systolic wave flow signifies elevated RA pressure, and hence PAH, and, in cases of severe Tricuspid Regurgitation, this wave may get totally reversed. Nagueh et al, found that if the ratio of TVI of systolic flow and the sum of the TVIs of systolic and diastolic flow < 55%, then mean RAP > 8 mmHg. 24 Pulmonary vascular resistance (PVR) is the most important parameter, especially for pre-capillary hypertension. An estimation of it can be done from the TR jet by measuring the peak velocity and TVI of TR jet and applying the following formula:

PVR =
Pulmonary Vascular Resistance is measured in Woods unit and the above formula pertains till a value of 8 WUs.
Pulmonary artery hypertension is a progressive disease with poor prognosis and the 1-, 2-and 3years survival rates are 87%, 76% and 67% respectively. Pericardial effusion, indexed right atrial area, degree of septal shift towards the right ventricle in diastole, TAPSE, pulmonary vascular resistance and Tei index have prognostic value in patients of pulmonary artery hypertension. 25

CONCLUSION
Thus, it is clear that Trans-thoracic echocardiographic evaluation of Right Heart has many facets. It can now be done with much ease and the plethora of parameters obtained have great diagnostic and prognostic importance. A detailed evaluation is hence mandatory for any echocardiographic study.
Declaration: Figure 1, and Table 6 published under CC4 have been adapted from literature and, as per requirement, have been appropriately cited with reference of author and publication journal. The remaining figures are author's own work. Data of rest of tables have been derived from sources appropriately referenced.