Pulmonary hypertension
The normal mean pulmonary artery pressure (PAPm) at rest is 14 ± 3 mmHg with an upper limit of normal of approximately 20 mmHg.
Pulmonary hypertension (PH) is as per newly updated guidelines defined as an increase in mean pulmonary arterial pressure (PAPm) ≥20 mmHg at rest as assessed by right heart catheterization.
It can be caused by a number of conditions including congenital and acquired diseases of the heart and/or lungs and systemic diseases.
Image 1 Clinical classification of PH
Galiè N, Humbert M, Vachiery JL, et al. ESC Scientific Document Group. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016 Jan 1;37(1):67-119. doi: 10.1093/eurheartj/ehv317. Epub 2015 Aug 29. PMID: 26320113.
Image 2 Haemodynamic definitions of PH
ECHOCARDIOGRAPHY
Echocardiography should always be performed when PH is suspected.
Pulmonary artery pressure (PAP)
To quantify pulmonary hypertension with echocardiography it is necessary to measure the maximal tricuspid regurgitation velocity with CW Doppler.
The calculation can be made from tricuspid valve velocity (v), estimated central venous pressure (CVP) or Right atrial pressure (RAP) and the Bernoulli equation.
The final calculation: PAPm=0.61*(4v2 + CVP/RAP) + 2
Alternatively, only systolic PAP can be measured PAPs=4v2 + CVP/RAP.
Both measurements (PAPm and PAPs) assume absence of pulmonic stenosis.
Image 3 Estimation of right atrial pressure
Image 4 Assessment of the PH probability based on echocardiography
Adapted from: Galiè N, Humbert M, Vachiery JL, et al. ESC Scientific Document Group. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016 Jan 1;37(1):67-119. doi: 10.1093/eurheartj/ehv317. Epub 2015 Aug 29. PMID: 26320113.
Estimation of sPAP can be alternativaly calculated = tricuspid regurgitation gradient + RA pressure
Image 5 Severity of PH classified by sPAP measurement (based on tricuspid regurgitation gradient + RA pressure)
Video 1 Moderate tricuspid regurgitation (2-3/4, mean PG measured at 80 mmHg) in a patient with severe pulmonary hypertension, A4C with colour Doppler, a regurgitant jet is seen in distal third of dilated right atrium.
Video 2 Moderate tricuspid regurgitation (2-3/4, mean PG 80 mmHg) in a patient with severe pulmonary hypertension, dilated rightr atrium, PLAX RV inflow view
Image 6 CW Doppler measurement of peak tricuspid regurgitation velocity, A4C view - peak TR velocity is 3,73 m/s. This velocity and is indicative of severe PH.
Video 3 Moderate TR in pulmonary hypertension - small central regurgitant jet is seen in colour Doppler.
Image 7 CW Doppler measurement of TR jet, A4C view - peak velocity is very high - 4,99 m/s. Calculated PAPs is 107,6 mmHg, PAPm is then 67,63 mmHg.
Video 4 IVC collapsing with respiration >50% of its diameter.
.gif)
Image 8 Inferior vena cava (IVC) diameter measured in subcostal view - the IVC is dilated to 22 mm and was collapsing >50%. RAP estimated at 8 mmHg.
Additional parametres that need to be assessed in patients with suspected PH
Evaluation of RV size and function should be performed and includes:
Signs of RV enlargement (from 4-chamber view):
- RV sharing apex with the LV
- RV being bigger than the LV
- RV basal diameter of >4.2 cm
- RV hypertrophy
Signs of RV hypertrophy (from subcostal view):
- RV end diastolic wall thickness >5 mm
Signs of RV systolic dysfunction:
- RV fractional area change <35%
- TAPSE< 1.7 cm
- RV tissue Doppler’s velocity < 10 cm/s at base of RV free wall
Signs of septal flattening:
- in systole = RV pressure overload
- in diastole = RV volume overload
Righ atrium enlargement
- Right atrial area (end-systole) >18 cm2
Evaluate for signs of elevated PVR:
- RVOT notching on pulse-wave Doppler profile is a sign of elevated PVR
Estimate volume status:
- Use size and collapsibility of IVC (during sniff maneuver) to determine RA pressure
- Hepatic vein flow: systolic flow reversal can be a sign of severe TR, RV overload, and/or increased RV stiffness
- Signs of RA overload/enlargement: RA area >18 cm2; interatrial septum bows from right to left
Evaluate severity of TR
- Features suggestive of severe TR include dense TR jet on continuous-wave Doppler, systolic flow reversal on hepatic vein pulse-wave Doppler imaging
Pulmonary artery
- Right ventricular outflow Doppler acceleration time <105 ms and/or mid-systolic notching (the normal PVAT is > 130 msec)
- Early diastolic pulmonary regurgitation velocity >2.2 m·s–1
- Pulmonary artery diameter >25 mm
Evaluate for pericardial effusion
- In patients with PAH, the presence of a pericardial effusion = poor prognostic sign
Evaluate for causes of PH (left heart disease, shunt lesions)
- Left heart disease: look for overt LV systolic dysfunction, grade 2 or worse diastolic dysfunction, severe aortic or mitral valvular disease, and less common abnormalities of the left heart (e.g., hypertrophic cardiomyopathy, cor triatriatum)
- Shunt lesions: perform agitated saline bubble study
1) Right ventricular enlargement
Image 9 Reference values for normal RV size
Video 5 Dilated right ventricle and right atrium in a patient with severe pulmonary hypertension.
Image10 RV dimensions measured in A4C view - basal diameter - 57mm, mid diameter 58 mm and longitudinal diameter 85 mm proves RV dilation.
Image 11 RVOT PLAX diameter of 44 mm corresponds to severely dilated RV (normal is <31 mm)
Video 6 The RV is bigger than LV in severe pulmonary hypertension
Video 7 Dilated RV outflow tract and pulmonary artery in PH, PSAX view - the pulmonary artery is dilated to 31mm, especially visibly in comparison with the aortic valve size. Normal diameter of Pulmonary artery is <25 mm.
Image 12 RVOT diameter measured in PSAX view - proximal RVOT diameter (left) of 33mm and distal RVOT diameter (right) of 32 mm.
2) RV systolic dysfunction
Three main parameters are most often measured - TAPSE, Fractional area change (FAC) and RV tissue Doppler velocity.
Image 13 Normal values for RV function
Image 14 Normal values for RV FAC
Image 15 Fractional area change (FAC) in pulmonary hypertension - the endocardial border of RV is first traced in end diastole (left) and then at end systole (right). The FAC is calculated at 21% and shows a moderate systolic dysfunction of RV.
Image 16 Tricuspid annular plane systolic excursion (TAPSE) measured in the same patient - the peak excursion is 14 mm (moderately lowered).
Image 17 Tissue Doppler imaging (TDI) of RV free wall in Pulmonary hypertension - peak S wave velocity is 9 cm/s - lower than the normal cutoff value suggests RV systolic dysfunction.
3) Systolic ‘flattening’ of the interventricular septum
Right ventricular pressure or volume overload causes the septum to be pushed towards the left ventricle in systole resulting in what is called “septal flattening” and ‘D’ shaped LV.
Normally the septum is concave towards the LV throughout the cardiac cycle and is an important part of biventricular function.
This shift causes alteration of the LV geometry and may lead to ventricular interdependence and in consequence to LV dysfunction.
Video 8 Systolic flattening of interventricular septum in a patient with severe precapillary PH - note the abnormal movement of the septum in systole and dilated RV with impaired mobility.
Video 9 Pulmonary hypertension, septal flattening and D shaped left ventricle, PSAX view
Video 10 Abnormal movement of the septum towards LV in PH, D shaped LV
Image 18 D-shaped left ventricle
4) Right atrial volume assessment
Enlargement of the right atrium, mostly due to pressure and/or volume overload is a pretty common finding in pulmonary hypertension.
RA area measured in A4C view < 18 cm2 is considered normal, higher values are a sign of RA enlargement/overload.
Video 11 Severely dilated right atrium in pulmonary hypertension, A4C view - note the right to left movement of the interatrial septum.
Image 19 Right atrial area measured in A4C view - are of 31,3 cm2 confirms severe dilation of the RA.
5) RVOT notching on pulse-wave Doppler profile is a sign of elevated PVR
Image 20 RVOT notching and also decrease acceleration time in a patient with pulmonary hypertension
Ginghină C, Muraru D, Vlădaia A, Jurcuţ R, Popescu BA, Călin A, Giuşcă S. Doppler flow patterns in the evaluation of pulmonary hypertension. Rom J Intern Med. 2009;47(2):109-21. PMID: 20067161.
6) Evaluation of pericardial effusion
Uncontrolled pulmonary hypertension can in some cases lead to development of pericardial effusion.
This is associated with significant morbidity and mortality.
The pericardial effusion further compromises cardiac hemodynamics and worsens the septal flattening and consequently the preload of the left ventricle.
Image 21 Pericardial effusion along the posterior and inferior wall of LV, pericardial echogenic separation 3mm in diameter
Other imaging modalities
A ventilation/perfusion lung scan
A ventilation/perfusion (V/Q) lung scan is a test of choice for screening patients with PH to look for CTEPH.
Normal V/Q scan effectively excludes the diagnosis CTEPH.
CT
CT scan may provide information suggesting PH and be helpful in diagnosis of the cause of PH, especially in case of CTEPH or lung disease.
High resolution CT is used in the diagnosis of diseases of the lung parenchyma such as interstitial lung disease or emphysema.
It can also be used to assess the accessibility of CTEPH to surgical treatment, although pulmonary angiography is also needed in most patients.
MR
Cardiac magnetic resonance (CMR) imaging can be used to assess morphology, function and blood flow of the heart including RV size, RV mass, stroke volume, cardiac output and pulmonary arterial distensibility.
However, CMR cannot be used to rule out PH.
Right heart catheterization
Right heart catheterization (RHC) is currently recommended to confirm the diagnosis PH and should preferably be performed in expert centres.
RHC is used to assess the severity PH and to help guide the treatment in subgroups of patients (PAH, congenital cardiac shunts and others). In addition, left heart catheterization should be performed in patients with systolic or diastolic dysfunction or heart failure and risk factors of coronary heart disease.
Cardiac catheterization should be performed after other tests (such as echocardiography, laboratory testing and other options mentioned above) have been completed. RHC procedure includes the following tests: pressure measurement (in the pulmonary artery, wedge position, right ventricle, right atrium), blood oximetry samples (from the superior vena cava, inferior vena cava and pulmonary artery or from additional sites), cardiac output measurement and more.
Overall recommendations and the diagnostic process as presented in the current PH guidelines are available below (Image 22 + 23)
Galiè N, Humbert M, Vachiery JL, et al. ESC Scientific Document Group. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016 Jan 1;37(1):67-119. doi: 10.1093/eurheartj/ehv317. Epub 2015 Aug 29. PMID: 26320113.
Management
Treatment of patients differs based on the cause of PH. Proposed diagnostic and treatment algorithm for patients with PAH is provided below. It includes pharmacotherapy as well as invasive procedures. Pharmacotherapy can be divided into background therapy and specific therapy. Background therapy includes the use of diuretics and anticoagulantion therapy.
Specific therapy includes the use of:
- calcium-channel blockers
- prostacyclins
- bosentan (a nonselective endothelin-A and -B receptor antagonist)
- ambrisentan (a selective endothelin-A receptor antagonist)
- macitentan (a nonselective endothelin-A and -B receptor antagonist)
- PDE-5 inhibitors (sildenafil, tadalafil)
- soluble guanylate cyclase stimulators (riociguat)
Lung transplantation and bridge to transplantation with extracorporeal life support and balloon atrial septostomy are used as non-pharmacological treatment modalities.
References
- Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M; ESC Scientific Document Group. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016 Jan 1;37(1):67-119. doi: 10.1093/eurheartj/ehv317. Epub 2015 Aug 29. PMID: 26320113.
- https://litfl.com/pulmonary-hypertension-echocardiography/
- McLaughlin VV, Shah SJ, Souza R, Humbert M. Management of pulmonary arterial hypertension. J Am Coll Cardiol. 2015 May 12;65(18):1976-97. doi: 10.1016/j.jacc.2015.03.540. PMID: 25953750.
- Christopher M. Ma, Joshua Cohen, Daniel Tolpin; Right Ventricular Dysfunction and the “D”-shaped Left Ventricle. Anesthesiology 2020; 132:155 doi: https://doi.org/10.1097/ALN.0000000000002961
- Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, Williams PG, Souza R. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 2019;53:1801913.
