PH in CHD

Pulmonary hypertension (PH) is not uncommon in adults with congenital heart disease (CHD), with a prevalence of 4.2%.¹ It can significantly affect patients' quality of life and increase their morbidity and mortality.^2,3 Hence, early diagnosis and appropriate management are essential for limiting symptoms and improving outcomes. Pulmonary arterial hypertension (PAH) associated with CHD belongs to group 1 of the international PH classification, characterized by pre-capillary PH, where there is a pulmonary artery wedge pressure (PAWP) ≤15 mmHg. There are 4 major types: Eisenmenger syndrome, PAH associated with prevalent left-to-right shunts, PAH with small/coincidental defects, and PAH after defect repair.^4,5 Even within these 4 types, there is significant variation according to the underlying anatomy and the type of prior interventions. Group 2 PH, distinguished by post-capillary hemodynamics (PAWP >15 mmHg), is commonly encountered as a result of systemic ventricular dysfunction or left-sided obstructions, such as mitral stenosis. Moreover, other types of PH related to CHD exist, including segmental PH and the pulmonary vascular disease (PVD) encountered in patients with a Fontan-type univentricular circulation, in whom even small increases in pulmonary vascular resistance (PVR) have detrimental effects in the absence of a sub-pulmonary ventricle.⁶

Limitations of Standard Echocardiographic Parameters in CHD

Echocardiography is the primary screening tool for PH and can identify patients who require further investigation, including right heart catheterization. PH guidelines describe several "standard" echocardiographic parameters, which increase the probability of PH when present. It is suggested that a raised peak tricuspid regurgitation (TR) velocity should be considered alongside other echocardiographic signs relating to the inferior vena cava, right atrium (RA), ventricles, and pulmonary artery (PA) when screening for PH.^5,7 There are, however, numerous exceptions to these "signs" in patients with CHD that are not within the scope of the guidelines and leave a gap in the recommendations when managing patients with CHD.

Our paper by Dimopoulos et al.⁸ in the Journal of the American College of Cardiology fills this gap in the recommendations. It is an expert opinion paper based on a systematic review and survey of experts. It focuses on both simple (e.g., pulmonary stenosis [PS]) and complex (e.g., unrepaired univentricular hearts or patients with systemic right ventricles) types of CHD. It highlights the importance of an in-depth understanding of the anatomy and pathophysiology of CHD and appropriate use and interpretation of echocardiography to identify CHD patients who have developed PH, ensuring early diagnosis and appropriate management.

To illustrate the above, we provide real-life examples of CHD in which echocardiography has been important in establishing the diagnosis (PH or other), but only when interpreted with caution and integrated with other investigations and expert clinical judgement.

Case 1: A Patient With an Unrecognised Atrial Septal Defect and Evidence of PH on Echocardiography

A 35-year-old female patient with a long-standing diagnosis of atypical asthma underwent echocardiography, which demonstrated right ventricular (RV) dilatation, raising the suspicion of PH (Video 1A-B). Additional echocardiographic signs of PH included RA and PA dilatation, and with a peak TR velocity of 3.7 m/s (Figure 1C-D). On cardiac catheterization (Table 1), mean PA pressure was elevated at 30 mmHg, with a normal pulmonary capillary wedge pressure. However, careful serial oximetry revealed a step-up in oxygen saturations between the high and low superior vena cava (SVC) and a further step-up in the RA, suggestive of a large left-right shunt. A diagnosis of superior sinus venosus atrial septal defect (ASD) with partial anomalous pulmonary venous drainage of the right upper and middle pulmonary veins into the SVC was confirmed on cardiac magnetic resonance imaging (Video 1C-D). Despite a high PA pressure, there was no evidence of PVD, with a PVR of 2.7 Wood Units and an estimated ratio of pulmonary systemic blood flow (Qp/Qs) of 2.1.

ASDs are one of the most common types of CHD and can present at any age with a murmur, as incidental findings on an echocardiogram, or with symptoms relating to the associated shunt. A large left-right shunt at atrial level typically results in RV and RA dilatation; the increase pulmonary blood flow can cause a rise in PA pressures, but a significant rise in PVR is uncommon.

• In all cases of suspected PH, CHD should be excluded on echocardiography, with further specialist work-up where there is an ongoing suspicion of CHD.
• Serial oximetry measurements should be performed at right heart catheterization, including high and low SVC sampling.
• PVR should always be calculated with care, remembering that the formula for calculating PVR uses Qp and not Qs in its denominator.

Video 1A

Video 1B

Video 1C

Video 1D

Figure 1

Table 1

Site	Pressure (mmHg)	Oxygen Saturation (%)
High SVC	-	72
Low SVC	-	76
Inferior vena cava	-	70
RA (mean)	12/7	87
RV (systolic/end diastolic pressure)	54/9	86
PA (systolic/diastolic/mean)	50/13/30	87
PAWP (mean)	5	94
Arterial	148/100/110	94

Case 2: A Patient With Severe Long-Standing PS Mimicking PH on Echocardiography

A 20-year-old male patient with severe learning difficulties and previous Ross procedure for aortic valve disease presented with breathlessness and peripheral edema. Echocardiography showed a severely dilated and impaired RV (Video 2, Figure 2B). The peak TR velocity was 5 m/s, suggestive of a RV systolic pressure of over 100 mmHg (Figure 2C). There was also severe RA dilation with deviation of the atrial septum to the left and an eccentricity index compatible with PH. The pulmonary valve could not be interrogated with the patient awake. However, on auscultation, there was a harsh ejection systolic murmur at the left upper sternal border. Investigations repeated under general anesthesia revealed very severe valvar stenosis of the bioprosthetic pulmonary valve, with a Doppler-derived peak pressure gradient of 86 mmHg (Figure 2D), confirmed on cardiac catheterization (Figure 2E), with no evidence of PH. This was successfully relieved by a percutaneous approach.

PS is a common form of CHD, accounting for 10% of cases. The major physiological sequela is increased RV afterload with consequent RV hypertrophy and, in advanced disease, RV dilatation and dysfunction. Without careful assessment of the RV outflow tract, this treatable condition may be missed and echocardiographic findings mistaken for PH.

• The pulmonary valve should be visualized and assessed by Doppler imaging in all cases of suspected PH.
• In PS or RV outflow tract obstruction, TR gradient ≠ PA pressure.
• An estimation of PA systolic pressure can be derived by subtracting the gradient across the RV outflow tract or pulmonary valve from the TR gradient. However, cardiac catheterization is necessary when one suspects coexistent PS and PH.

Video 2

Figure 2

Case 3: Complex Pulmonary Atresia in Tetralogy of Fallot, Complicated by Segmental PH

A 50-year-old female patient with a history of pulmonary atresia with a ventricular septal defect (VSD) presented with small-volume hemoptysis, raising the suspicion of PH. She had undergone surgery for bilateral modified Blalock-Taussig shunts in early childhood (to augment pulmonary blood flow with placement of a tube graft between each subclavian artery and branch PA). Echocardiography confirmed features consistent with the medical history (Figure 3, Video 3A). The peak TR gradient was very high but was not helpful for diagnosing PH because the RV was not in communication with the pulmonary circulation but rather with the left ventricle (LV) through the VSD (Figure 3C). Continuous wave Doppler interrogation of the right Blalock-Taussig shunts, however, revealed a low peak velocity of 2.2 m/s, which reflects a reduced pressure gradient between the aorta and the pulmonary segment fed by the shunt (usually >4 m/s). This was strongly suggestive of PH in at least one lung segment (Video 3B, Figure 3E). Cardiac computed tomography supported the diagnosis, displaying the absent main PA but significant dilatation of a more peripheral PA (Figure 3F).

Pulmonary atresia with a VSD is at the most severe end of the spectrum of tetralogy of Fallot and ranges from confluent pulmonary arteries to complete absence of the pulmonary arteries. Pulmonary blood flow may be supplied by a patent ductus arteriosus and/or by major aortopulmonary collateral vessels and may require augmentation in childhood (e.g., with Blalock-Taussig shunts). PH may develop in areas of the pulmonary circulation receiving excessive flow and often manifests as segmental PH.9 Cardiac catheterization is required to confirm this diagnosis, but echocardiography and other imaging (and auscultation) may raise the suspicion of segmental PH.

• In pulmonary atresia, the TR gradient and other standard echocardiographic criteria for diagnosing PH do not apply.
• PA dilatation on echocardiography or other imaging can raise suspicion of PH.
• A low peak Doppler velocity on modified views of aortopulmonary collateral vessels or surgical shunts may be suggestive of segmental PH.

Figure 3

Video 3A

Video 3B

Case 4: Unrepaired Univentricular Heart and Eisenmenger Physiology

A 45-year-old male patient with unrepaired univentricular circulation (double inlet left ventricle [DILV]) and previous pacemaker implantation presented with increasing exercise intolerance (New York Heart Association functional Class III). He was cyanotic, with resting oxygen saturations of 85%, a hemoglobin of 240 g/L, and platelets of 68 x 10⁹/L. Echocardiography confirmed the DILV with ventriculoarterial discordance (Video 4, Figure 4B). There was no gradient across the pulmonary valve (between the LV and PA), hence the pulmonary circulation was "unprotected" (Figure 4C-E), confirming the diagnosis of Eisenmenger physiology in this adult patient.

Univentricular hearts encompass a broad category of CHD, characterized by both atria related entirely or almost entirely to a functionally single ventricular chamber.¹⁰ Typically, there is an accompanying hypoplastic ventricle, precluding biventricular repair. In the absence of significant obstruction of flow toward the pulmonary circulation (no PS), exposure to systemic pressures causes PVD to develop in childhood, with systemic levels of PVR (often referred to as Eisenmenger physiology) in adult patients. Conversely, in patients with univentricular hearts and severe PS, the lungs may be "protected," allowing little or no PVD to develop; however, they may require augmentation of pulmonary blood flow (e.g., Blalock-Taussig shunts). A case of DILV with severe PS is shown in Figure 4F-H.

• In adult patients with univentricular hearts, a diagnosis of PH can be made with good confidence on echocardiography by confirming the intracardiac morphology and absence of significant PS.
• Because atrioventricular (AV) valves are connected to the systemic ventricle, neither the peak TR nor mitral regurgitation Doppler gradient reflect PA pressures.
• Pulmonary valve hemodynamics (Table 2) can be useful when screening for PH.

Video 4

Figure 4

Table 2⁸

Guideline Echocardiographic Parameter of PH (by Anatomic Location)	Useful Application of Parameter in
	Atrial Septal Defect	Pulmonary Stenosis	Tetralogy of Fallot with Pulmonary Atresia	Univentricular Circulation	Transposition of the Great Arteries After Atrial Switch Operation
Inferior vena cava diameter >21 mm with reduced inspiratory collapse	⚠	⚠	—	—	⚠
RA area >18 cm2	⚠	⚠	—	—	⚠
Raised peak TR velocity	⚠	⚠	—	—	—
RV/LV basal diameter ratio >1	⚠	⚠	—	—	⚠
LV eccentricity index >1.1	⚠	⚠	—	—	⚠
RV outflow Doppler <105 ms	⚠	⚠	—	⚠	✔
PA diameter >25 mm	⚠	⚠	✔	✔	✔
Early diastolic PR velocity >2.2 m/s	⚠	⚠	—	✔	✔
✔ can be used, with caution ⚠ requires adaptation/significant caution when interpreting — not possible/not applicable due to anatomical considerations

Case 5: Progressive LV Dilatation in a Patient Following a Mustard Procedure for Transposition of Great Arteries

A 22-year-old male patient, who had undergone an atrial switch operation for transposition of the great arteries (TGA) as an infant, attended clinic with progressive breathlessness, fatigue, and cyanosis. Echocardiography demonstrated a dilated sub-pulmonary LV with significant systolic dysfunction and a surprisingly small systemic RV (Video 5). There was an early diastolic PR velocity of 3.9 m/s measured from the PR jet (Figure 5B-C) and a shortened pulmonary acceleration time of 62 ms (Figure 5D). PAH was diagnosed on cardiac catheterization, with no post-capillary component.

TGA is an uncommon cyanotic CHD. The arterial switch procedure is currently used, but this was not possible in previous decades. The Mustard operation is a type of "atrial switch repair, which involves the creation of pathways that redirect the systemic and pulmonary venous return within the atria. However, patients with an atrial switch procedure end up with a systemic RV that is typically dilated and hypertrophied, with the tricuspid valve in the sub-systemic position. In rare cases, however, when PVD develops, the sub-pulmonary LV becomes dilated and impaired, as seen in this case.

• Progressive dilatation of the sub-pulmonary LV, with pseudo-normalization of the RV/LV diameter ratio, may be a sign of PH in patients who have had an atrial switch procedure.
• The tricuspid valve is connected to the systemic RV; therefore, the peak TR velocity does not reflect pulmonary pressures and cannot be used to diagnose PH. Instead, the peak mitral regurgitation velocity may provide information on PA pressure, accounting for the presence of any PS.
• Additional echocardiographic signs of PH for patients with atrial switch may be used and are listed in Table 2.
• Cardiac catheterization is essential to confirm the rise in PVR and exclude post-capillary PH relating to systemic RV dysfunction, TR, or pulmonary venous pathway obstruction.

Video 5

Figure 5

Key Points

1. Echocardiography remains a fundamental part of the routine assessment of all patients with CHD. This should follow a protocolized approach that includes screening for PH.
2. Although international guideline recommendations do apply to many patients with CHD, they do not in others, and expert clinical judgment is required.
3. All patients with CHD should be followed by expert centers, where direct or indirect signs of PH can be identified early and managed in an appropriate setting.
4. A major role of noninvasive screening for PH is to identify patients who have increased PA pressures and would therefore benefit from cardiac catheterization. Invasive catheterization is the only way to distinguish between pre- and post-capillary PH and calculate PVR in a reliable manner.

References

1. Duffels MG, Engelfriet PM, Berger RM, et al. Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry. Int J Cardiol 2007;120:198-204.
2. Diller GP, Kempny A, Inuzuka R, et al. Survival prospects of treatment naïve patients with Eisenmenger: a systematic review of the literature and report of own experience. Heart 2014;100:1366-72.
3. van Riel AC, Schuuring MJ, van Hessen ID, et al. Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification. Int J Cardiol 2014;174:299-305.
4. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 2009;119:2250-94.
5. Galiè N, Humbert M, Vachiery JL, et al. 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;37:67-119.
6. Dimopoulos K, Wort SJ, Gatzoulis MA. Pulmonary hypertension related to congenital heart disease: a call for action. Eur Heart J 2014;35:691-700.
7. 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;102:ii14-22.
8. Dimopoulos K, Condliffe R, Tulloh RMR, et al. Echocardiographic Screening for Pulmonary Hypertension in Congenital Heart Disease: JACC Review Topic of the Week. J Am Coll Cardiol 2018;72:2778-88.
9. Dimopoulos K, Diller GP, Opotowsky AR, et al. Definition and Management of Segmental Pulmonary Hypertension. J Am Heart Assoc 2018;7:e008587.
10. Khairy P, Poirier N, Mercier LA. Univentricular heart. Circulation 2007;115:800-12.

Keywords: Hypertension, Pulmonary, Heart Defects, Congenital, Ventricular Dysfunction, Left, Echocardiography, Pulmonary Circulation, Pulmonary Atresia, Pulmonary Valve, Pulmonary Artery, Tricuspid Valve, Heart Ventricles, Mitral Valve Insufficiency, Dilatation, Ductus Arteriosus, Patent, Blood Platelets, Atrial Fibrillation, Cardiac Catheterization, Eisenmenger Complex, Hemodynamics, Dyspnea, Pacemaker, Artificial, Oxygen, Hemoglobins, Cyanosis, Auscultation, Pulmonary Veno-Occlusive Disease, Transposition of Great Vessels, Tetralogy of Fallot, Blalock-Taussig Procedure

< Back to Listings