Table of content (clickable):
Abnormal PA pressure defined (> 3 months of age):
Normal PA pressure usually around sPAP: 15 mmHg and dPAP: 5 mmHg (mean of 10) after 3 months of age
Mean PAP ≥ 20 mmHg (measured by cath but can be estimated by echocardiography using the pulmonary insufficiency jet)
Highly suspect increased PA pressure if systolic PAP ≥ 40 mmHg, estimated by echocardiography
Usually through a tricuspid regurgitant jet velocity estimating a RV-RA gradient and assuming RA pressure between 0-5 mmHg (although may underestimate RA pressure in the context of RV diastolic dysfunction)
In the presence of a PDA or VSD shunt - may use velocity gradient to estimate systolic PA pressure, by evaluating the directionality and systemic systolic blood pressure at the time of echocardiography.
R to L post-tricuspid shunt systolic velocity gradient: systolic systemic BP + gradient = estimation of systolic pulmonary arterial pressure
L to R post-tricuspid shunt systolic velocity gradient: systolic systemic BP - gradient = estimation of systolic pulmonary arterial pressure
PDA/VSD may not satisfy fully the assumptions of the Bernoulli equation.
In the context of unrestrictive post-tricuspid shunt, the systolic PA pressure will be, by definition, close to systemic as:
An unrestrictive left to right ventricular septal defect will transmit flow and pressure in systole in the pulmonary vascular bed and sPAP will approximate systemic systolic blood pressure by pressure transmission from the left ventricle into the right ventricle,
An unrestrictive left to right patent ductus arteriosus septal defect will transmit flow and pressure in systole and diastole in the pulmonary vascular bed and sPAP will approximate systemic systolic blood pressure by pressure transmission from the aorta to the pulmonary artery.
One may have increased pulmonary pressure due to a left to right shunt (pressure and/or flow transmission). This may not mean that there is underlying increase pulmonary vascular resistance as: Pressure factors Flow x Resistance. As such, an infant with a large left to right ductus arteriosus (or VSD) will have by definition equalization of pressure on both sides of the ductus (two connected compartments will equalize in pressure). This will lead to septal motion flattening (and increased eccentricity index) secondary to increase pulmonary arterial pressure by systemic pressure transmission. Once the shunt is removed, PA pressure may normalize and underlying pulmonary vasculature may be with adequate pulmonary vascular resistance.
We assume that echocardiography-estimated RV systolic peak pressure approximates systolic pulmonary arterial pressure in the absence of structural cardiac anomaly
First 3 months: PVR dropping and PA pressures should be < systemic (if systemic within normal for age).
Mourani PM, Sontag MK, Younoszai A, Miller JI, Kinsella JP, Baker CD, Poindexter BB, Ingram DA, Abman SH. Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2015 Jan 1;191(1):87-95. doi: 10.1164/rccm.201409-1594OC. PMID: 25389562; PMCID: PMC4299632.
This study used this definition for suspicion of PH by echocardiography: "The primary criteria for PH were met by any of the following findings: an estimated right ventricular systolic pressure (RVSP) greater than 40 mm Hg, RVSP/systemic systolic blood pressure greater than 0.5, any cardiac shunt with bidirectional or right-to-left flow, or any degree of ventricular septal wall flattening."
Nawaytou H, Hills NK, Clyman RI. Patent ductus arteriosus and the risk of bronchopulmonary dysplasia-associated pulmonary hypertension. Pediatr Res. 2023 Feb 17. doi: 10.1038/s41390-023-02522-4. Epub ahead of print. PMID: 36804505.
"An echocardiogram was considered positive for PH if the tricuspid regurgitant jet velocity was >2.9 m/s (RV-RA of 33.6 mmHg), the PDA systolic flow velocity estimated a peak systolic pulmonary artery pressure >35 mmHg, or if systolic septal flattening was present (based on end-systolic eccentricity index >1.0)."
"The PH was considered to be flow-associated PH, due to the presence of a left-to-right PDA shunt (in the absence of a VSD), if there was left-to-right flow through the PDA in both systole and diastole and the echocardiographic signs of PH disappeared following ductus closure."
"An echocardiogram was classified as positive for PVD if it met the above criteria for PH in the absence of a PDA or VSD shunts. If a PDA or VSD shunt was present, the echocardiogram was only classified as positive for PVD if it met the above criteria for PH and there was bidirectional or right-to-left flow through the PDA or VSD, or left-to-right flow through a moderate/large PDA without holodiastolic flow reversal in the abdominal aorta."
Faqih SA, Noto-Kadou-Kaza B, Abouamrane LM, Mtiou N, El Khayat S, Zamd M, Medkouri G, Benghanem MG, Ramdani B. Pulmonary hypertension: prevalence and risk factors. Int J Cardiol Heart Vasc. 2016 May 9;11:87-89. doi: 10.1016/j.ijcha.2016.05.012. PMID: 28616531; PMCID: PMC5462628.
In the adult literature using echocardiography to evaluate pulmonary arterial pressure: "A value greater than or equal to 35 mm Hg is considered PAH and classified as follows: mild PAH (35–50 mm Hg), moderate PAH (50–70 mm Hg), and severe pulmonary hypertension (> 70 mm Hg)"
Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, Carlsen J, Coats AJS, Escribano-Subias P, Ferrari P, Ferreira DS, Ghofrani HA, Giannakoulas G, Kiely DG, Mayer E, Meszaros G, Nagavci B, Olsson KM, Pepke-Zaba J, Quint JK, Rådegran G, Simonneau G, Sitbon O, Tonia T, Toshner M, Vachiery JL, Vonk Noordegraaf A, Delcroix M, Rosenkranz S; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-3731. doi: 10.1093/eurheartj/ehac237. Erratum in: Eur Heart J. 2023 Feb 23;: PMID: 36017548.
Probably of PH by echocardiography recommended in the adult population:
TRJ > 3.4 m/s (46 mmHg of RV-RA gradient)
TRJ between 2.9 (33.6 mmHg) and 3.4 m/s with at least one of:
LV end-systolic eccentricity index >1.1
RV/LV basal diameter ratio >1.0
Tricuspid annular plane systolic excursion (TAPSE)/sPAP <0.55 mm/mmHg,
RVOT acceleration time (PAAT) <105 ms or midsystolic notching,
Early diastolic pulmonic insufficiency velocity >2.2 m/s,
Increased pulmonary artery diameter >25 mm,
Estimated right atrial pressure ≥15 mmHg,
Right atrial area >18 cm2.
TRJ 2.9 to 3.4 m/s without other indices listed above
TRJ is ≤2.8 m/s and at least one indirect indices listed above is present.
TRJ ≤2.8 m/s with no other indices (listed above).
Koestenberger M, Apitz C, Abdul-Khaliq H, Hansmann G. Transthoracic echocardiography for the evaluation of children and adolescents with suspected or confirmed pulmonary hypertension. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and D6PK. Heart. 2016 May;102 Suppl 2:ii14-22. doi: 10.1136/heartjnl-2014-307200. PMID: 27053693.
"Usually TR velocity (TRV) values >3.4 m/s, corresponding to a PASP >50 mm Hg at rest, make PAH highly likely in adults." - This cut-off was established when definition for PAS was considered to be mPAP >25 mmHg. This definition has now been reviewed for a mPAP >20mmHg. As such, we locally use a value of TRV corresponding to a PASP > 40 mmHg (TRV 35 + expected RA pressure of 5 mmHg = 40 mmhg) as our local cut-off for "Echocardiographically-suspected PH".
Pre-capillary pulmonary hypertension official definition by catheterization (Pulmonary Arterial Hypertension) - click here for reference:
mPAP > 20 mm Hg
Pulmonary arterial wedge pressure or LV end-diastolic pressure ≤ 15 mm Hg
PVR index ≥ 3 Woods unit ×m2
Diastolic transpulmonary gradient ≥ 7 mm Hg
From: Changes in systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) during gestation. (Lakshminrusimha and Saugstad, 2016).
Systemic HTN = abnormal high BP in systemic compartment. Similarly, pulmonary hypertension (PH) = ”Abnormally” High pressure in PA
Etiologies of systemic hypertension: idiopathic, renal, cancer, steroids, etc.
One must identify the cause to tailor treatment
PH is a symptom of underlying process: Congenital heart, BPD, HIV, Pulmonary Embolus, Mitral Regurgitation, PPHN…
Similary to systemic HTN, one must identify cause to tailor treatment in a case of PH.
Etiologies have different pathophysiology and management:
Hypoplastic pulmonary vasculature (TOF-MAPCA, pulmonary hypoplasia)
High PVR, such as in acute PH of newborns (ie: PPHN) with disturbed transition to extra-uterine life
Pulmonary Embolus, pulmonary thromboembolic diseases
Congenital heart defect, such as Large PDA or Aortic to PA window: equalization of pressure during Systole and Diastole between Aorta and PA, pulmonary vasculature is exposed to excessive pressure and volume = PA has pressure similar than Aorta (depending on restrictive of PDA) = PH.
Post-Capillary, such as in: obstruction of pulmonary veins, severe mitral regurgitation, LV disease with poor drainage of venous return and backflow in pulmonary circulation
Tricuspid regurgitation jet velocity gradient
During systole, tricuspid valve is closed (prevents backflow in RA)
As RV pressure starts rising and RV dilates, the annulus dilates and coaptation of valve becomes less competent. TR appears: blood flow from high pressure RV to low pressure RA generates a velocity of low.
Measuring speed using Doppler allows to estimate the “gradient” (difference) between RV and RA chamber at peak of systole
Simplified Bernoulli equation tells you that :
Pressure difference between the 2 cavities = 4 x velocity2
True if the opening of jet is a narrow point.
Assuming RA pressure – 0-5mmHg (will increase with diastolic RV dysfunction)
TR = 5.45 m/s à 119 mmHg at peak of systole à RV-RA gradient of 119 mmHg
Assuming RA pressure about 5 mmHg: estimate of systolic PAP = 119+5 = 124 mmHg
Continuous-wave (CW) Doppler captures the velocity of flow across the entire line of interrogation (versus Pulsed-Wave (PW) Doppler captures the velocity of flow at the selected interrogation cursor).
TR obtained from the PLAX view and estimating RV-RA gradient of 33.6 mmHg - Providing an estimate of RV peak systolic pressure at 39 mmHg
TR obtained from the Apical view and estimating RV-RA gradient of 92 mmHg - Providing an estimate of RV peak systolic pressure at 97 mmHg (assuming RA pressure at 5 mmHg - likely underestimated in the context of RV failure leading to increased RA pressure)
Significant RV failure and dilation in the context of severe pulmonary hypertension.
As pressure rises on RV side (or pressure decreases on LV side), it can become iso-systemic (same as pressure on the LV compartment) or supra-systemic (higher pressure than on RV side).
Because there is a shared wall:
Isosystemic (>2/3 systemic) = Flat Interventricular septum at peak of contraction - D-Shape LV
Supra-systemic = Bowing septum into the LV cavity
With persistent increased afterload, RV hypertrophies and dilate
Case of acute pulmonary hypertension of the newborn (PPHN):
Parasternal long axis indicating underfilled LV (from low pulmonary vascular flow) and dilated RV outflow tract.
Sweep in parasternal short axis indicating almost pancaking of left ventricle. RV is dilated and septum is bowing at times in systole into the LV cavity at mid-papillary level. LV is underfilled due to the persistence of increased pulmonary vascular resistance.
RV function is preserved despite increased pulmonary afterload. TR appears (mild) due to RV strain.
RV peak systolic pressure is estimated using the TR jet peak velocity. RV-RA gradient of 58 mmHg (based on modified Bernouilli equation; 4 x 3.81 x 3.81). Assuming a RA pressure of about 5 mmHg, estimated peak systolic RV pressure of 63 mmHg. Assuming normal cardiac anatomy, systolic Pulmonary Arterial Pressure estimated at 63 mmhg. This patient had a systolic blood pressure (systemic) of 45 mmHg. Hence, supra-systemic pulmonary pressures.
LV end-systolic eccentricity index as a way to quantify septal deformation
Eccentricity index (RV-LV Interaction: D1/D2) (Normal < 1.23)
RV/LV ratio (marker of RV dilation: D3/D2) (Normal < 1.00)
Jone JG, Ivy D, Frontiers in Pediatrics - November 2014 , Volume 2, Article 124
Nagiub M, Echocardiography 2015;32:819–833
The following image is from the above article. The article outlines:
Systolic septal flattening recognized at EIs ≥ 1.15.
High inter-observer agreement for EIs.
Quantitative parameters of RV systolic function were impaired only at EIs ≥ 1.3.
Reference: Echocardiography 2016;33:910–915
From King ME et al. Circulation 1983. - "Marked exaggeration of this configurational change occurred in patients with right ventricular systolic hypertension (right ventricular systolic pressure greater than 50% systemic pressure), with progressive loss of curvature from end-diastole (0.45 ± 0.05) to end-systole (0.19 ± 0.06)."
Often assessed by septal-curvature (shared wall)
At peak of systole, when both contracted, pulmonary and aortic valve are open à RV equalize with pressure in PA; LV equalize with Aorta.
Usually LV under higher pressures than RV in systole (contraction)
LV round and RV crescentic (surrounds LV) in systole
Flattening only assessed at end systole on cross-sectional view (parasternal short axis)
Flat in diastole indicative of similar pressure in RV-LV during diastole (ex: volume overload from ASD, severe RV failure with diastolic dysfunction)
Pulmonary insufficiency - CW-Doppler
Same concept as TR
Pulmonary valve is closed during diastole
If RV/PA dilation à PV annulus dilate, valve becomes less competent à Pulm Ins.
Early Insufficiency jet speed gives you estimate of mean PA pressure; end diastolic of diastolic PA pressure
Diastolic pulm pressure (DPAP) estimated from pulm regurgitation jet from velocity of end-diastolic PI velocity
DPAP = 4 (end-diastolic PI velocity)2 + estimated RA pressure*
mPAP = 4 (early diastolic PI velocity)2 + estimated RA pressure*
*estimated RA pressure = RV end-diastolic pressure
PAAT/RVET - Pulmonary artery acceleration time / Right ventricular ejection time
PW-Doppler of the RVOT – indicates pulmonary arterial flow velocity profile
Usually parabolic smooth acceleration and deceleration
With increase afterload – shorter acceleration
Adjusted by Ejection time to take into consideration heart rate
Pulmonary artery acceleration time on RV ejection time
PAAT/RVET (< 0.3 suggestive of PVD)
Mid-systolic notch with significant afterload increase due to recoil of pulmonary arterial wall
From: Steven A. Goldstein MD; Echo in Pulmonary HTN, ASE - Georgetown University Medical Center MedStar Heart Institute
PV stenosis suspected if mean gradient ≥ 4 mmHg on echo
CW-Doppler of the Right to Left PDA - Peak systolic gradient indicates that the PA pressure is 46 mmHg above the aortic pressure.
RV-LV cross-talk - Inter-Atrial shunt:
•LA-RA assessment of PFO/Atrial shunting reflects end-diastolic pressure relationships (influenced by MR-TR)
•With severe PH – RV diastolic dysfunction, increased RV end-diastolic pressures and bidirectional, eventually R to L shunt (and retrograde flow in hepatic veins with diastolic dysfunction).
Ventricular Septal Defect:
Relationship between LV and RV
Restrictive L to R with peak gradient of 20 means that LV pressure is 20 points > RV pressure when Aortic / Pulmonary valves open. If systolic BP is 60, sPAP is 40 (60 – 20 = 40)
If large and unrestrictive – will expose RV and pulmonary circulation (unless pulmonary stenosis) to systemic systolic pressures (and increases Qp:Qs)
Relationship between Aorta and PA
If large and L à R: expose pulmonary circulation to systemic pressures in systole/diastole
If restrictive and bidirectional: isosystemic PA pressures
Right to left: Suprasystemic PA pressures
When restrictive, may estimate PA pressures with Bernouilli equation (with caveat that PDA tubular and not a narrow point - hence, there may be some velocity attenuation through the course of the ductus)
Common Pulmonary Vasodilators:
New avenues under investigation for pulmonary arterial vasodilation
Acute vasoreactivity testing from PHA (Click here)
"Interpretation/Positive test: The 2009 ACC/AHA and 2015 ESC/ERS guidelines define a positive study based on a reduction in the mean pulmonary artery pressure of at least 10 mmHg to an absolute mean PA pressure of less than 40 mm Hg with a stable or improved cardiac output. Patients should have normal oxygen saturation prior to starting inhaled nitric oxide so that one can assess the true response on pulmonary vascular tone and not response to improved oxygenation."
"Acute vasoreactivity testing in children is undertaken to assess the response of the pulmonary vascular bed to pulmonary specific vasodilators. Similarly, the current practice in children with IPAH or familial PAH (isolated PVHD) is to use AVT to define the likelihood of response to long-term treatment with CCB therapy and for prognosis. There are 2 definitions of responders to AVT in IPAH or isolated PHVD, including 1) a decrease in mPAP of at least 10 mmHg to below 40 mmHg with a normal or increased increase in cardiac output; and 2) a decrease in mean PAP = 20% and increase or no change in CI and decrease or no change in PVR:SVR. AVT in children with PH associated with congenital heart disease (CHD) is undertaken to assess if the PVR will decrease sufficiently for surgical repair to be undertaken in borderline cases. In general, positive AVT for borderline cases with post tricuspid shunts is defined as decreases in PVRI to < 6-8 WUm2 or PVR:SVR <0.3. However, AVT is only one measure used to define operability and the whole clinical picture, the age of the patient and the type of lesion need to be taken into consideration. AVT may be studied with iNO (20–80 ppm), 100% oxygen, inhaled or intravenous PgI2 analogues, intravenous adenosine or sildenafil."
Apitz C, Hansmann G, Schranz D. Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart. 2016 May;102 Suppl 2:ii23-9. doi: 10.1136/heartjnl-2014-307340. PMID: 27053694.
From this important resource here: https://heart.bmj.com/content/102/Suppl_2/ii23 :
"Barst criteria, 1986: decrease in mPAP of ≥20%, unchanged or increased cardiac index, and decreased or unchanged PVR to SVR ratio (PVR/SVR);
Rich criteria, 1992: decrease in mPAP and PVR of ≥20%;
Sitbon criteria, 2005: decrease in mPAP of ≥10 mm Hg reaching an mPAP value of ≤40 mm Hg, and an increased or unchanged cardiac output."
Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, Hanna BD, Rosenzweig EB, Raj JU, Cornfield D, Stenmark KR, Steinhorn R, Thébaud B, Fineman JR, Kuehne T, Feinstein JA, Friedberg MK, Earing M, Barst RJ, Keller RL, Kinsella JP, Mullen M, Deterding R, Kulik T, Mallory G, Humpl T, Wessel DL; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; and the American Thoracic Society. Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society. Circulation. 2015 Nov 24;132(21):2037-99. doi: 10.1161/CIR.0000000000000329. Epub 2015 Nov 3. Erratum in: Circulation. 2016 Jan 26;133(4):e368. PMID: 26534956.
Hansmann G, Koestenberger M, Alastalo TP, Apitz C, Austin ED, Bonnet D, Budts W, D'Alto M, Gatzoulis MA, Hasan BS, Kozlik-Feldmann R, Kumar RK, Lammers AE, Latus H, Michel-Behnke I, Miera O, Morrell NW, Pieles G, Quandt D, Sallmon H, Schranz D, Tran-Lundmark K, Tulloh RMR, Warnecke G, Wåhlander H, Weber SC, Zartner P. 2019 updated consensus statement on the diagnosis and treatment of pediatric pulmonary hypertension: The European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by AEPC, ESPR and ISHLT. J Heart Lung Transplant. 2019 Sep;38(9):879-901. doi: 10.1016/j.healun.2019.06.022. Epub 2019 Jun 21. PMID: 31495407.
PPHNet individual membership form
March 27, 2023: You can now become an individual member to the Pediatric Pulmonary Hypertension Network (PPHNet). The membership form is attached here. You can also access it via the QR code or via the direct link here.
27 mars 2023: Vous pouvez maintenant devenir membre individuel du Pediatric Pulmonary Hypertension Network (PPHNet). Le formulaire d'adhésion est joint ici. Vous pouvez également y accéder via le code QR ou via le lien direct ici.