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Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British Society of Echocardiography

Pulmonary hypertension is defined as a mean arterial pressure of ≥25 mmHg as confirmed on right heart catheterisation. Traditionally, the pulmonary arterial systolic pressure has been estimated on echo by utilising the simplified Bernoulli equation from the peak tricuspid regurgitant velocity and adding this to an estimate of right atrial pressure. Previous studies have demonstrated a correlation between this estimate of pulmonary arterial systolic pressure and that obtained from invasive measurement across a cohort of patients. However, for an individual patient significant overestimation and underestimation can occur and the levels of agreement between the two is poor. Recent guidance has suggested that echocardiographic assessment of pulmonary hypertension should be limited to determining the probability of pulmonary hypertension being present rather than estimating the pulmonary artery pressure. In those patients in whom the presence of pulmonary hypertension requires confirmation, this should be done with right heart catheterisation when indicated. This guideline protocol from the British Society of Echocardiography aims to outline a practical approach to assessing the probability of pulmonary hypertension using echocardiography and should be used in conjunction with the previously published minimum dataset for a standard transthoracic echocardiogram.


Introduction
The British Society of Echocardiography (BSE) Education Committee has previously published a minimum dataset for a standard adult transthoracic echocardiogram (1). This document specifically states that the minimum dataset is usually only sufficient when the echocardiographic study is entirely normal. However, the BSE Education Committee has published a number of supplementary guidelines to cover specific pathologies to be utilised in conjunction with this minimum dataset.
The intended benefits of such supplementary recommendations are to: • Support cardiologists and echocardiographers to develop local protocols and quality control programmes for an adult transthoracic study. • Promote quality by defining a set of descriptive terms and measurements, in conjunction with a systematic approach to performing and reporting a study in specific disease states. • Facilitate the accurate comparison of serial echocardiograms performed in patients at the same or different sites.
In this guideline, the important measurements that should be performed when assessing a patient's probability of having pulmonary hypertension (PH) are discussed. Some of these views are part of the minimum dataset but the majority are additional. The aim of this document is to provide practical recommendations for the image and analysis dataset required in patients being assessed for possible PH, or where the diagnosis is known and is consistent with the 2015 European Society of Cardiology/European Respiratory Society recommendations on the diagnosis and treatment of PH (2). Estimation of PH in patients with left heart disease such as valvular heart disease remains within current guidelines (3,4,5). Estimation of pulmonary artery pressure (PAP) within these patients is reasonable, at rest and during exercise (3,6) or during follow-up of an individual patient. However, confirmation with right heart catheterisation (RHC) should be considered, particularly if the presence of PH is a major component of any decision to refer for intervention. This guideline replaces the previous protocol on PH published by the BSE and will be reviewed and updated in the future as a result of future publications or changes in best practice.

Background
PH is presently defined as an increase in mean pulmonary arterial pressure to ≥25 mmHg at rest as assessed by right heart catheterisation (2). The clinical significance of a mean pulmonary arterial pressure between 21 mmHg and 24 mmHg is unclear. It can complicate many cardiovascular, respiratory and connective tissue diseases. Untreated, morbidity and mortality levels are high (7,8) and therefore accurate and prompt diagnosis is crucial. The diagnosis of PH requires a clinical suspicion based on symptoms, physical examination and review of a comprehensive set of investigations. Echocardiography is a key imaging modality in the assessment of patients with suspected or known PH.
The classification of PH categorises different clinical conditions into five groups (Table 1). This is an important categorisation for two reasons: first, the most common form of PH encountered in any echocardiography department will be secondary to left heart disease (9) and hence a full study with consideration of indirect measures of elevation in left ventricular end-diastolic pressure must be performed in all cases consistent with the minimum dataset (1); secondly, the interpretation of supportive measurements for classification of patients with intermediate probability of PH, such pulmonary artery acceleration/mid systolic notching, must be taken in the context of the possible underlying cause as these may be more likely in cases with pre-capillary PH.
Each of these groups can further be categorised as to whether there is normal pulmonary arterial wedge D X Augustine et al. pressure (an estimate of left atrial pressure) or elevated pulmonary arterial wedge pressure, which may be helpful in identifying the aetiology of PH. The World Health Classification of PH is outlined in Table 1.

BSE pulmonary hypertension guideline
The traditional echocardiographic approach to estimating pulmonary artery systolic pressure (PASP) uses a derivation of right ventricular pressure from the tricuspid regurgitation (TR) velocity added to a qualitative assessment of right atrial pressure (RAP). Previous studies have demonstrated good correlation across patient populations but only moderate precision of absolute PASP values calculated from TR velocity (TRV)max (11,12,13,14). This is important as in an individual patient, significant under and over estimation can occur leading to misdiagnosis and inappropriate treatment (15).
There are number of reasons why the level of agreement between the estimated pressures derived by echocardiography and those measured invasively is poor. First, errors may occur in accurate measurement of the peak TRV signal. This can result in both over estimation and underestimation if the quality of the Doppler signals is poor or inaccurate as a result of suboptimal Doppler alignment due to eccentric jets. When estimating right ventricular systolic pressure (RVSP) from the TRV using the Bernoulli equation, the TRV is squared and multiplied by 4, so even small errors in the absolute measurement of TRV can result in significant changes to the estimate of RVSP. Secondly, in order to obtain an estimate of PASP, the RVSP needs to be added to an estimate of the RAP derived from measurement of the inferior vena cava (IVC) dimensions and response to inspiration. However, in many patients, IVC dimensions cannot be obtained and even in those where measurement is possible, the accuracy between echo estimation of RAP and invasive measurement is as low as 34% (16). Thirdly, it is well recognised that in patients with severe free-flowing TR that the correlation between TRV and RVSP is poor and should not be performed (17). In addition, absence of TR is insufficient to exclude the presence of PH. For example, one study has shown that in patients with scleroderma being screened for PH, if a TRV cut-off of 2.7 m/s was used, this would have excluded some patients who had a mean pulmonary arterial pressure >40 mmHg (18). Furthermore, the expected normal upper limit of PASP depends on BMI (19).
In view of these factors, when screening patients with suspected PH, information obtained from echocardiography can only grade the probability of PH being present rather than provide a definitive diagnosis. Therefore, when assessing the probability of PH, the measurement of TRV should be used in conjunction with other echocardiographic markers of PH. Thus, the information in this protocol is intended to be used as a guide and the data have been selected by consensus using as much evidence base as possible. Future studies assessing the accuracy of this probability-based approach in the diagnosis of PH will be beneficial and add to the evidence base. The invasive measurement of pulmonary artery pressure during right heart cardiac catheterisation is required to confirm or refute a diagnosis of PH. The first step in assessing the echocardiographic probability of PH being present is to measure the peak TRV. If this is a good-quality signal and is greater than 3.4 m/s, there is a high probability of PH being present. If the peak TRV is below 3.4 m/s, the probability of PH is assessed in combination with other echocardiographic markers.
This approach based on estimation of likelihood is recommended for all clinical groups of PH. Additional considerations in specific subsets of patients are included in the 'Appendices' section. The assessment of probability of PH by echocardiography is just one part in the overall clinical judgement as to the presence of PH in a certain individual. Echocardiographic findings should be interpreted alongside other clinical findings to establish the likelihood of PH prior to confirmatory diagnosis as needed by RHC.

Echocardiographic assessment of patents with PH
The flow chart depicted in Fig. 1 is used to assess the probability of PH. The echocardiographic parameters used for grading the probability of PH are set out in Table 2 and described further in Table 3. If the TRV is >3.4 m/s then the echocardiographic probability of PH is high. If the TRV is ≤3.4 m/s, then other echocardiographic parameters suggesting PH must be used to assign the probability of PH. These parameters are split into three categories (A: the ventricles; B: the pulmonary artery; C: the IVC and right atrium). Parameters from at least two different categories are needed to determine the probability of PH.
Echocardiography also provides information about aetiology and prognosis in patients with PH. Patients with established PH or high probability for PH should have full assessment to exclude left-sided heart disease or intracardiac shunts as the cause of PH. Right ventricular dilatation and dysfunction are considered poor prognostic markers in patients with PH. Additional measurements that can be used to assess patients with PH are shown in Table 4.

Additional measurements
Although not required when determining the likelihood of PH being present, a number of other echo markers can be useful in determining the severity of PH and may provide additional prognostic information (Table 4). These are particularly useful in those patients with a confirmed diagnosis of PH. These markers include right ventricular dimensions (RVD1 RVD2, RVD3), fractional area change and tricuspid annular plane systolic excursion (TAPSE). In addition, the peak systolic RV pulsed tissue Doppler velocity taken at the lateral tricuspid annulus and right ventricular index of myocardial performance (RIMP) can provide further information.  A4C (M-mode) This is an angle dependent measurement and therefore it is important to align the M-mode cursor along the direction of the lateral tricuspid annulus. Select a fast sweep speed The excursion of the lateral tricuspid annulus is measured by M-mode between end diastole and peak systole A measure of longitudinal RV systolic function. TAPSE <1.7 cm is highly suggestive of RV systolic dysfunction (33)

Other echocardiographic measurements
In addition to the echocardiographic measures discussed in this document, there are other echocardiographic markers that may be of use in assessing patients with PH. These measures include stroke volume, cardiac output and pulmonary vascular resistance, although the value of serial measures of these by echocardiography has not been validated. These measures may be of value where further haemodynamic information is required: • Pulmonary arterial end-diastolic pressure (PDP).

Mean PAP = 4(PRV BD ) 2 + RAP
• Surrogates of heart function (e.g. stroke volume index and cardiac index) have been shown to be associated with prognosis (32,34). It is possible to estimate these values using echocardiography (Table 5) although the preferred option would be by thermodilution at RHC (2).

Appendices TR assessment
Peak TR velocity is the key parameter in determining the probability of PH, but the TR signal can be absent in a proportion of patients. The prevalence of TR in patients with a PASP ≥35 mmHg is only 80% but increases to greater than 95% in those with PASP >50 mmHg (36). If the TR signal is absent, probability estimation should be based on clinical context taking into consideration other concordant clinical and echocardiographic signs of RV pressure overload (Fig. 1). In patients with a trivial TR jet or sub optimal continuous wave Doppler spectrum, injection of intravenous agitated saline can be considered to improve the Doppler signal allowing measurement of peak TR velocity (37) (Fig. 3). As a default, if clinical suspicion remains, invasive measurement of pulmonary pressures should be recommended.
In patients with severe TR, TR velocity can be significantly underestimated and cannot be used alone to exclude PH. The severity of the volume of TR is distinct from velocity and the probability of PH in this context should be determined in conjunction with other echocardiographic parameters (Fig. 1).

Assessment of PH in patients with left heart disease
This guideline endorses the use of a probabilitybased approach for the assessment of PH in all clinical subgroups including those secondary to left-sided heart disease. A full assessment including history, ECG and echocardiography will help to identify PH due to left heart disease (38). This is important as left heart disease will be the major aetiology of PH encountered in echocardiography departments (9). If there is an intermediate or high probability of PH then further echocardiographic evaluation should be made to exclude a cardiac cause for PH. In particular, this should prompt a careful assessment of LV systolic and diastolic function, measurement of left atrial volume and exclusion of leftsided valve disease (Table 6). Colour flow Doppler should be used to exclude atrial and ventricular septal defects. Following a thorough clinical review, a bubble study and transoesophageal echocardiogram may be considered to fully exclude cardiac causes of PH, especially in those patients with confirmed PH.
It is recognised that some guidelines use an absolute PASP value to guide management of patients with PH secondary to left heart disease. In patients with severe   (3,4). Evidence for this is largely based on invasive pulmonary artery pressure measurements, but there are limited echocardiographic studies suggesting a prognostic role for PASP derived from TR velocity and RA pressure (41,42). In this subset of patients, in addition to determining probability of PH using TR velocity, resting PASP can be estimated by echocardiography using standard methods (4). Confirmation by invasive measurement is required before considering valve surgery if elevated PASP is the main or only reason triggering intervention.

Key messages
In patients with suspected PH, the following echo parameters should be used to assess the probability of PH: