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Heart, Lung and Circulation

Management of Adults With Congenital Heart Disease and Pulmonary Arterial Hypertension in the UK: Survey of Current Practice, Unmet Needs and Expert Commentary

Open AccessPublished:November 13, 2017DOI:https://doi.org/10.1016/j.hlc.2017.10.018

      Background

      Pulmonary arterial hypertension (PAH) is a well-recognised complication of adult congenital heart disease (CHD). However, management is not currently standardised between centres and specific guidelines are lacking. In order to identify and understand the unmet needs related to PAH associated with CHD (PAH-CHD), a survey of physicians was performed.

      Methods

      An electronic survey was sent to two physician groups: (1) cardiologists registered in a UK cardiology directory; (2) specialist pulmonary hypertension (PH) physicians known to manage patients with adult PAH-CHD. The questions related to referral pathways, screening, therapy and palliative care.

      Results

      821 surveys were distributed and 106 were returned. Respondents included a broad mix of specialist physicians with many patients along with general cardiologists managing only a small number of PAH-CHD patients. Although 97% of respondents have access to a specialist PH centre, patients are still being managed in non-specialist settings. Shared care arrangements are widespread but only 41% have formal shared care protocols. Palliative care services are limited and general cardiologists rarely perform 6-minute walk tests (6MWT) or quality of life assessments. People with PAH-CHD are often undertreated, with 39% of respondents reporting that fewer than 25% of these patients were receiving PAH-specific therapies.

      Conclusions

      The survey revealed gaps and inconsistencies in the management of patients with PAH-CHD therefore patient-specific guidance is needed for many of these aspects.

      Keywords

      Introduction

      Pulmonary arterial hypertension (PAH) is defined as a mean pulmonary arterial pressure of ≥25 mmHg at rest, with a pulmonary artery wedge pressure or left atrial pressure ≤15 mmHg and pulmonary vascular resistance (PVR) >3 Wood units [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Gatzoulis M.A.
      • Beghetti M.
      • Landzberg M.J.
      • Galie N.
      Pulmonary arterial hypertension associated with congenital heart disease: recent advances and future directions.
      ]. Congenital heart disease (CHD) that causes unrestricted pressure and volume overload of the pulmonary circulation can lead to PAH [
      • Dimopoulos K.
      • Wort S.J.
      • Gatzoulis M.A.
      Pulmonary hypertension related to congenital heart disease: a call for action.
      ]. Recent paediatric medical and surgical advances have enabled people with CHD to live longer, leading to an increase in the number of patients who go on to develop PAH associated with CHD (PAH-CHD) [
      • Gatzoulis M.A.
      • Beghetti M.
      • Landzberg M.J.
      • Galie N.
      Pulmonary arterial hypertension associated with congenital heart disease: recent advances and future directions.
      ]. The 2015 UK audit of specialised PH centres reported a rate of 17 people with PAH due to CHD per million of the population [

      National Audit of Pulmonary Hypertension 2015 [21.12.2016]. Available from: http://content.digital.nhs.uk/catalogue/PUB20043/nati-pulm-hype-audi-2015-rep.pdf.

      ]. Five to ten per cent of adults with CHD also have PAH [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ].
      The European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines provide recommendations for the management of PAH-CHD [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. However, evidence to support the use of PAH-specific therapies in CHD is limited and the management is not standardised, with variation between treating centres and clinicians.
      The Congenital Heart disease And pulMonary arterial hyPertension: Improving Outcomes through education and research Networks (CHAMPION) program was set up to improve the care of patients with PAH-CHD in the UK and to help inform clinician decision-making. Objectives include identification of evidence gaps, unmet needs, challenges associated with the management, and development of educational resources and initiatives to ensure sharing of best practice. Within this remit, a survey was conducted to gain an understanding of the challenges faced by physicians in the day-to-day management of PAH-CHD in the UK. This publication covers various aspects of patient management, presenting the survey results and providing expert commentary on each aspect.

      Methods

      Respondents and Inclusion/Exclusion Criteria

      The survey targeted both general cardiologists and experts in PAH-CHD and therefore included two groups of clinicians: those proposed by the CHAMPION Steering Committee as currently managing these patients, and all adult cardiologists registered with the UK Directory of Cardiology (http://cardiodirectory.co.uk) with an email address. This second source was used to ensure that physicians who manage PAH-CHD outside specialist centres were also identified and included. At the start of the survey, consenting respondents were asked to confirm whether they worked in a general cardiology department, specialist adult CHD centre or specialist PH centre, and that they managed PAH-CHD. Other respondents were excluded from the survey. An introductory email, followed by two reminder emails, was sent to all participants together with a hyperlink to the survey. All responses were anonymised, but some demographic information was requested and analysed.

      Survey

      The survey was electronically administered using a professional survey website (SurveyMonkey, Palo Alto, CA, USA) (see Supplementary Figure S1 for survey questions). Questions were either multiple choice or answered by five-point Likert scales or free text comment boxes. Prior to the survey, a pragmatic literature review of PAH-CHD was performed and used by the CHAMPION Steering Committee to identify unmet needs related to their care. As part of the survey, respondents were asked to rank these unmet needs in order of importance. For each unmet need, weighted averages were calculated by assigning five points for each first place ranking, four points for each second place, etc. The total was divided by the number of respondents in order to determine an average ranking for each unmet need. Categorical values were presented as numbers (percentage).

      Results and Expert Commentary

      Respondent Characteristics

      A total of 821 physicians were invited to participate in the survey and 106 responded. Demographic information is shown in Table 1. The proportion of respondents managing more than 50 people with PAH-CHD per year was 33%, hence many worked in a specialised setting. However, 56% of respondents described themselves as general cardiologists and 42% of respondents managed less than 10 people with PAH and CHD annually. Four of the respondents were from a PAH specialist centre. We have shown that 47% of respondents were from the South and London, where the majority of specialist PH centres are located. Eighteen of 55 (33%) of respondents saw >50% PAH-CHD patients annually, of these 5/18 (28%) stated that they worked in a general cardiology department (so therefore were NOT either PH specialists or ACHD specialists).
      Table 1Respondent characteristics.
      Characteristic
      Not all respondents provided demographic information.
      n/N%
      Geographic region of practice
       North5/3216
       Midlands and East6/3219
       South, excluding London12/3238
       London3/329
       Scotland4/3213
       Northern Ireland0/320
       Wales2/326
      Speciality
       General physician0/320
       Rheumatologist0/320
       Respiratory physician2/326
       General cardiologist18/3256
       ACHD cardiologist12/3238
       Paediatric cardiologist0/320
      Years in practice
       <5 years0/320
       5 to 15 years4/3213
       >15 years28/3288
      Years in practice as a consultant
       <5 years8/3125
      5 to 15 years13/3141
       >15 years10/3131
      Approximate number of PAH-CHD patients seen annually
      Respondents were asked to specify for the year 2015.
       <1023/5542
       10 to 4914/5526
       50 to 10013/5524
       >1005/559
      n/N: Number of respondents with each characteristic/Total number of respondents who completed the question.
      Abbreviations: ACHD, adult congenital heart disease; PAH-CHD, pulmonary arterial hypertension associated with congenital heart disease.
      a Not all respondents provided demographic information.
      b Respondents were asked to specify for the year 2015.

      Unmet Needs in the Management of Pulmonary Arterial Hypertension Associated with CHD

      The unmet needs in the management of people with PAH-CHD were previously identified by the Steering Committee. When asked to rank these, respondents were in broad agreement (Table 2). The five unmet needs considered to be most important by the Steering Committee are discussed below.
      Table 2Unmet needs identified by the Steering Committee: Ranking by survey respondents.
      Unmet needs and rank (n = 30)Rank
      Ranking was assigned in descending order according to % of respondents who indicated the unmet need within their top 5, followed by weighted average in cases where % was identical.
      %
      % of respondents who indicated that this was one of their top 5 unmet needs.
      Weighted average
      5 points were assigned for each 1st place ranking, 4 points for each 2nd place ranking, 3 points for each 3rd place ranking, 2 points for each 4th place ranking and 1 point for each 5th place ranking. The average was calculated by dividing by the total number of points assigned to each unmet need by the total number of respondents who provided a ranking for that need.
      Development of a standardised approach to the care of PAH-CHD patients across centres1603.3
      Establishment of a screening protocol for PAH in CHD patients2533.7
      Definition of treatment targets for different PAH-CHD subgroups3532.6
      National guidance on when to initiate and escalate PAH-specific therapies in PAH-CHD patients4503.3
      Guidance on risk stratification for PAH-CHD patients5473.4
      Guidance on how to manage non-Eisenmenger’s syndrome patients6403.1
      Guidance on non-pharmacological therapy for PAH-CHD patients7402.8
      Establishment of a registry to determine the size and characteristics of the PAH-CHD population8333.1
      Palliative care strategy9332.8
      Identification of biomarkers and other non-invasive strategies for screening CHD patients for PAH10302.4
      Management of Down’s syndrome patients11272.4
      Creation of a biobank of CHD samples for genomic analysis12202.0
      n: Number of respondents who completed the question.
      Abbreviations: PAH-CHD, pulmonary arterial hypertension associated with congenital heart disease; PAH, pulmonary arterial hypertension; PH, pulmonary hypertension; CHD, congenital heart disease.
      a Ranking was assigned in descending order according to % of respondents who indicated the unmet need within their top 5, followed by weighted average in cases where % was identical.
      b % of respondents who indicated that this was one of their top 5 unmet needs.
      c 5 points were assigned for each 1st place ranking, 4 points for each 2nd place ranking, 3 points for each 3rd place ranking, 2 points for each 4th place ranking and 1 point for each 5th place ranking. The average was calculated by dividing by the total number of points assigned to each unmet need by the total number of respondents who provided a ranking for that need.

      Standardised Approach to Care

      Seven adult and one paediatric centre were designated in 2001 to provide specialist PH services in the UK (see Supplementary Table S1). Each centre has to meet standards including the use of specialist nurses and expert consultants providing 24-hour care, prescription and monitoring of PAH therapies in addition to collection of data for the annual UK National PH audit. Furthermore, the National Health Service, England recently conducted a review of CHD services in order to standardise patient care [
      NHS England New Congenital Heart Disease Review: Final Report.
      ]. Current UK adult CHD services comprise regional networks of specialist adult CHD (including surgical) and local adult CHD centres. The proportion of respondents who referred people with PAH-CHD to a specialist PH centre was 97% (57% of whom were general cardiologists and respiratory physicians) (see Table 3). The majority of respondents (81%) share the management of patients with a specialist PH centre, with 56% of respondents reporting having a shared care clinic within their own unit. Shared care is driven by physicians with an interest in PH, enabling the diagnosis, prescribing and monitoring of people with PAH-CHD to be provided at the patient’s adult CHD centre. Formal shared care protocols were in place in only 41% of shared care clinics (see Table 3), revealing a lack of adherence to the recommendations outlined in the 2015 New CHD review, which states that all Level one and Level two adult CHD centres are required to have evidence of joint protocols of care with a national PH centre [
      NHS England New Congenital Heart Disease Review: Final Report.
      ].
      Table 3Referral/care pathways for PAH-CHD patients.
      Elements of careRespondents who answered yes
      n/N%
      Do your PAH-CHD patients attend the following types of clinic?
      Respondents could specify more than one type of clinic.
       General cardiology clinic15/4434
       Specialist ACHD clinic27/4461
       Specialist PAH-CHD clinic23/4452
       General PH clinic6/4414
      In your centre do you refer patients to a specialist PH service?
      35/3697
      Do you share management of patients with a specialist PH service?
      29/3681
      Do you have a shared care clinic within your own unit?
      18/3256
      Do you have a written, formal shared care protocol with a specialist PH centre?
      13/3241
      Do your PAH-CHD patients have access to the following specialist staff?
      Nominated PAH clinician27/4461
      PAH specialist nurse
      Included only responses that stated≥1 full time equivalent nurse.
      14/4233
      PAH specialist pharmacist8/4219
      n/N: Number of respondents who answered yes/Total number of respondents who completed the question.
      Abbreviations: PAH-CHD, pulmonary arterial hypertension associated with congenital heart disease; PAH, pulmonary arterial hypertension; PH, pulmonary hypertension; ACHD, adult congenital heart disease.
      a Respondents could specify more than one type of clinic.
      b Included only responses that stated ≥ 1 full time equivalent nurse.
      The proportion of respondents that ranked the need for a standardised approach to the care of PAH-CHD as one of their top five unmet needs was 60% (Table 2) and highlighted the need for clearer referral pathways and easier access to specialist PH centres (see Supplementary material survey data slides). Furthermore, although 61% of respondents reported that patients had a nominated PH physician, specialist PH nurses and specialist pharmacists were reported by only 33% and 19% of respondents respectively as being available, indicating that certain aspects of specialist care are lacking (Table 3). Current ESC/ERS guidelines recommend that specialist PH centres should follow at least 50 patients on PAH treatment with at least two new referrals per month [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. They should be able to offer full diagnostic services including computerised tomography, magnetic resonance imaging and right heart catheterisation and should have specialist nurse support [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. Furthermore, they should be able to offer all PAH therapies available in that country and should also enrol patients in clinical trials [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. Although specialist adult CHD centres may be able to fulfil many of these requirements, they may not be able to offer more complex therapies such as therapies targeting the prostacyclin pathway and, therefore, a clear referral link with a designated PH centre is vital.

      Screening

      The importance of identifying CHD patients with a high PVR has long been accepted [
      • Wood P.
      The Eisenmenger syndrome or pulmonary hypertension with reversed central shunt.
      ]. This is achieved by estimating pulmonary artery pressure on echocardiography and referring for cardiac catheterisation. It, therefore, comes as no surprise that physician awareness of the potential for pulmonary vascular disease in CHD is high, with more than 90% of respondents reporting that they screen all patients with atrial septal defects, ventricular septal defects, systemic-to-pulmonary shunts and complex defects and 83% screen patients with repaired left-to-right shunts for late development of PH (Table 4). Furthermore, 92% of respondents screen patients either periodically or at every clinic visit, with just 8% only screening for PAH at the initial clinic visit (Table 4). These data confirm that clinicians managing CHD routinely assess pulmonary haemodynamics; such screening should remain part of the long-term management of these patients.
      Table 4Screening for PAH in CHD patients.
      Aspects of ScreeningRespondents who answered yes
      n/N%
      Do you consider PH when evaluating each of the following groups of patients?
      Respondents could specify more than one group of patients.
       ASD34/3694
       VSD34/3694
       Systemic to pulmonary shunts35/3697
       Operated left to right shunts30/3683
       Complex defects33/3692
       Other3/368
      When do you screen CHD patients for PAH?
       First evaluation only3/368
       Every time I review them22/3661
       Periodically11/3631
      n/N: Number of respondents who selected this option/Total number of respondents who completed the question.
      Abbreviations: ASD, atrial septal defect; CHD, congenital heart disease; PAH, pulmonary arterial hypertension; VSD, ventricular septal defect.
      a Respondents could specify more than one group of patients.

      Initiation and Escalation of Therapy/Risk Stratification

      Table 5 summarises therapy recommendations for PAH-CHD patients. The survey revealed that many people with PAH-CHD are not receiving treatment, with almost 40% of respondents reporting a low usage of PAH-specific therapies (defined as less than 25% receiving a PAH-specific therapy) (Table 6). The proportion of respondents reporting low usage of PAH-specific therapies was greater among those working in general cardiology departments than among those working in specialist adult CHD centres (49% versus 18%, respectively) (Figure 1). These data suggest that patients may benefit from further assessment in a specialist setting. Over half (56%) of respondents with a high case load of Eisenmenger’s syndrome (defined as more than 50% of their PAH patients) reported high or very high usage of PAH-specific therapies (defined as 50–74% or 75–100%), as compared with 30% (17/56) for all respondents combined. Conversely, among respondents with prevalent systemic-to-pulmonary shunts accounting for more than 50% of all people with PAH-CHD, only 11% (1/9) reported high or very high usage of PAH-specific therapies. This reflects differences in the guidance for PAH-specific therapies for each of the CHD subtypes.
      Table 5Therapy recommendations for PAH-CHD patients.
      PAH-CHD classificationRecommended treatmentsESC/ERS recommendation (class/level of evidence)
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      Evidence to date
      Eisenmenger’s syndromeBosentan
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      IBBREATHE 5
      • Galie N.
      • Beghetti M.
      • Gatzoulis M.A.
      • Granton J.
      • Berger R.M.
      • Lauer A.
      • et al.
      Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study.
       + BREATHE 5 OLE
      • Gatzoulis M.A.
      • Beghetti M.
      • Galie N.
      • Granton J.
      • Berger R.M.
      • Lauer A.
      • et al.
      Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study.
      Eisenmenger’s syndromeOther ERAs, PDE5is and prostanoids should be considered
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      IIaCData from retrospective, observational studies and small RCTs
      • Blok I.M.
      • van Riel A.C.
      • van Dijk A.P.
      • Mulder B.J.
      • Bouma B.J.
      From bosentan to macitentan for pulmonary arterial hypertension and adult congenital heart disease: Further improvement.
      ,
      • Mukhopadhyay S.
      • Nathani S.
      • Yusuf J.
      • Shrimal D.
      • Tyagi S.
      Clinical efficacy of phosphodiesterase-5 inhibitor tadalafil in Eisenmenger syndrome–a randomized, placebo-controlled, double-blind crossover study.
      ,
      • Mukhopadhyay S.
      • Sharma M.
      • Ramakrishnan S.
      • Yusuf J.
      • Gupta M.D.
      • Bhamri N.
      • et al.
      Phosphodiesterase-5 inhibitor in Eisenmenger syndrome: a preliminary observational study.
      ,
      • Rosenzweig E.B.
      • Kerstein D.
      • Barst R.J.
      Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects.
      ,
      • Zuckerman W.A.
      • Leaderer D.
      • Rowan C.A.
      • Mituniewicz J.D.
      • Rosenzweig E.B.
      Ambrisentan for pulmonary arterial hypertension due to congenital heart disease.
      PAH associated with prevalent systemic to pulmonary shuntsSelected cases may benefit from closure. As data are lacking, no recommendations can be made for or against the use of PAH-specific therapies
      • Dimopoulos K.
      • Wort S.J.
      • Gatzoulis M.A.
      Pulmonary hypertension related to congenital heart disease: a call for action.
      NAData from observational study
      • Blok I.M.
      • van Riel A.C.
      • van Dijk A.P.
      • Mulder B.J.
      • Bouma B.J.
      From bosentan to macitentan for pulmonary arterial hypertension and adult congenital heart disease: Further improvement.
      PAH with small/coincidental defects
      Many patients with small defects are considered to be idiopathic PAH patients with a coexistent defect and hence are eligible for treatment.
      Avoid defect closure, treat with PAH-specific therapies
      • Dimopoulos K.
      • Wort S.J.
      • Gatzoulis M.A.
      Pulmonary hypertension related to congenital heart disease: a call for action.
      NAData from RCTs and observational study
      • Blok I.M.
      • van Riel A.C.
      • van Dijk A.P.
      • Mulder B.J.
      • Bouma B.J.
      From bosentan to macitentan for pulmonary arterial hypertension and adult congenital heart disease: Further improvement.
      ,
      • Galie N.
      • Rubin L.
      • Hoeper M.
      • Jansa P.
      • Al-Hiti H.
      • Meyer G.
      • et al.
      Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial.
      PAH after defect correctionDo not close residual defects. Treat with PAH-specific therapies
      • Dimopoulos K.
      • Wort S.J.
      • Gatzoulis M.A.
      Pulmonary hypertension related to congenital heart disease: a call for action.
      NAData from RCTs with PAH-CHD subgroup
      • Galie N.
      • Brundage B.H.
      • Ghofrani H.A.
      • Oudiz R.J.
      • Simonneau G.
      • Safdar Z.
      • et al.
      Tadalafil therapy for pulmonary arterial hypertension.
      ,
      • Galie N.
      • Ghofrani H.A.
      • Torbicki A.
      • Barst R.J.
      • Rubin L.J.
      • Badesch D.
      • et al.
      Sildenafil citrate therapy for pulmonary arterial hypertension.
      ,
      • Pulido T.
      • Adzerikho I.
      • Channick R.N.
      • Delcroix M.
      • Galie N.
      • Ghofrani H.A.
      • et al.
      Macitentan and morbidity and mortality in pulmonary arterial hypertension.
      ,
      • Rosenkranz S.
      • Ghofrani H.A.
      • Beghetti M.
      • Ivy D.
      • Frey R.
      • Fritsch A.
      • et al.
      Riociguat for pulmonary arterial hypertension associated with congenital heart disease.
      ,
      • Simonneau G.
      • Barst R.J.
      • Galie N.
      • Naeije R.
      • Rich S.
      • Bourge R.C.
      • et al.
      Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial.
      ,
      • Sitbon O.
      • Channick R.
      • Chin K.M.
      • Frey A.
      • Gaine S.
      • Galie N.
      • et al.
      Selexipag for the Treatment of Pulmonary Arterial Hypertension.
      . Data from observational study
      • Blok I.M.
      • van Riel A.C.
      • van Dijk A.P.
      • Mulder B.J.
      • Bouma B.J.
      From bosentan to macitentan for pulmonary arterial hypertension and adult congenital heart disease: Further improvement.
      NA: No specific recommendations are provided in the ESC/ERS Guidelines.
      Abbreviations: ERA, endothelin receptor antagonist; ERS, European Respiratory Society; ERS, European Society for Cardiology; OLE, open label extension; PAH, pulmonary arterial hypertension; PAH-CHD, pulmonary arterial hypertension associated with congenital heart disease; PDE5i, phosphodiesterase type 5 inhibitor; RCT, randomised controlled trial; BREATHE 5, The Bosentan Randomized Trial of Endothelin Antagonist Therapy-5.
      a Many patients with small defects are considered to be idiopathic PAH patients with a coexistent defect and hence are eligible for treatment.
      Table 6Management of PAH-specific therapy in PAH-CHD patients.
      Aspects of PAH-specific therapy managementRespondents
      n/N%
      Approximately what percentage of your PAH-CHD patients are currently receiving a PAH-specific therapy?
       0 to 24%22/5639
       25 to 49%17/5630
       50 to 74%14/5625
       75 to 100%3/565
      Do you initiate and manage PAH-specific therapies for patients with PAH-CHD?
       Yes, both initiate and manage22/6335
       Yes, manage but not initiate12/6319
       No, I refer all patients who need PAH specific therapies to a PH specialist29/6346
      Which therapies do you initiate/manage?
      Respondents could specify more than one therapy.
       Sildenafil30/30100
       Bosentan25/3083
       Ambrisentan20/3067
       Macitentan16/3053
       Tadalafil15/3050
       Riociguat7/3023
       Iloprost i.v.7/3023
       Epoprostenol i.v.6/3020
       Iloprost inhaled5/3017
       Treprostinil s.c.1/303
       Treprostinil i.v.1/303
       Vardenafil0/300
      Do you perform walk tests for your PAH-CHD patients?
       Yes25/4161
       No16/4139
      Do you measure quality of life for your PAH-CHD patients?
       Yes19/4050
       No20/4050
      n/N: Number of respondents who selected this option/Total number of respondents who completed the question.
      Abbreviations: i.v., intravenous; PAH-CHD, pulmonary arterial hypertension associated with congenital heart disease; PH, pulmonary hypertension; s.c., subcutaneous.
      a Respondents could specify more than one therapy.
      Figure 1
      Figure 1Proportion of PAH-CHD patients treated with PAH-specific therapies, classified according to the type of practice.
      Abbreviations: ACHD, adult congenital heart disease; PAH-CHD, pulmonary arterial hypertension associated with congenital heart disease.
      To further explore how therapy is initiated and managed in people with PAH-CHD, the survey respondents were asked whether they initiate and/or manage therapy, or whether they refer all patients who need PAH-specific therapy to a PH specialist. Over half (54%) of respondents stated that they initiate and/or manage specific therapies (Table 6). Of these, 35% reported both initiating and managing specific therapies, while the remainder only manage therapies after initiation by another clinician. The survey indicates that therapy is more likely to be initiated by physicians working in specialist centres than in general cardiology departments; 65% of respondents from specialist adult CHD centres both initiate and manage PAH-specific therapies, whereas this was only true for 15% of respondents working in general cardiology departments, possibly leading to under-treatment.
      Bosentan is widely used in PAH-CHD patients (83% of respondents who initiate/manage therapy) (see Table 6). This frequent use is likely due to the fact that bosentan is the only therapy with a class I recommendation in Eisenmenger’s syndrome patients in the ESC/ERS guidelines [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. A current trial is being undertaken with macitentan (MAESTRO, Clinical study to assess the efficacy, safety, and tolerability of macitentan in subjects with Eisenmenger Syndrome; ClinicalTrials.gov Identifier: NCT01743001) and should report in 2017. All respondents reported managing patients using phosphodiesterase type −5 inhibitors, which is likely the result of the wide availability of sildenafil, low cost and clear commissioning guidance supporting sildenafil as first-line treatment for all PAH patients in the UK; 67% and 53% of respondents reported that they also managed patients with the endothelin receptor antagonists ambrisentan and macitentan, respectively. In total, 43% of respondents reported that they managed their patients using prostanoids (Table 6). A greater use of prostanoids was reported among specialist PH and adult CHD centres (61%) versus general cardiology clinics (15%).
      Once a patient with PAH has been initiated on therapy, the current ESC/ERS guidelines recommend regular assessment in specialist PH centres to collect prognostic information, including exercise testing, which allows stratification of patients in a low (estimated 1-year mortality <5%), intermediate (estimated 1-year mortality 5 to 10%) or high risk (estimated 1-year mortality >10%) group. If patients do not meet their treatment goals, and their response to therapy is deemed inadequate, the treatment regimen should be escalated [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. In the current study, 39% of respondents (the majority working in general cardiology units) reported that they do not perform walk tests, while these are routinely performed in specialist PH centres (Table 6). In this survey, 50% of respondents also stated that they do not perform quality of life assessments (90% of these worked in general cardiology units). Quality of life is an important treatment goal in PAH [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ] and a decreasing quality of life has been shown to be a determinant of mortality in people with PAH-CHD [
      • Blok I.M.
      • van Riel A.C.
      • Schuuring M.J.
      • Duffels M.G.
      • Vis J.C.
      • van Dijk A.P.
      • et al.
      Decrease in quality of life predicts mortality in adult patients with pulmonary arterial hypertension due to congenital heart disease.
      ], highlighting the need for regular assessment.
      There were four responses from PH specialists. One was not managing PAH-CHD patients so did not proceed with the survey beyond q. 2 and another did not proceed beyond q. 4: Which therapies do you initiate/manage. Therapies initiated or managed were: Respondent 1: bosentan, macitentan, iloprost i.v., iloprost inhaled, treprostinil; respondent 2: bosentan, macitentan, ambrisentan, epoprostenol i.v., iloprost inhaled. Both respondents saw 50–100 patients annually and for respondent 1, 50–74% were on PAH specific therapy, and for respondent 2, 0–24% were. Both performed the 6MWT twice a year and both used the emPHasis-10 quality of life questionnaire.
      In summary, the results of this survey indicate that many patients with PAH-CHD are not being treated with PAH-specific therapies. This may, in part, be because many patients are still managed in general cardiology clinics. The ESC/ERS guidelines recommend that PAH care should take place in specialist PH centres that routinely manage PAH-specific drug therapies and can prescribe all such therapies available in a particular country [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. Patients who are managed in non-specialist centres may have less access to therapy, have lower awareness of available treatment options and do not routinely undergo exercise testing and quality of life assessment. Improving referral pathways and access to specialist centres, both raised as issues to be addressed by the survey respondents, may lead to an increase in the use of PAH-specific therapy for people with PAH-CHD. The lack of specific treatment recommendations for PAH-CHD subtypes other than Eisenmenger’s syndrome needs to be addressed.

      Non Pulmonary Arterial Hypertension-Specific Therapy

      Non-pharmacological and supportive therapy are important components of the clinical management of PAH. This is reflected in the results of the current survey, with 40% of respondents stating that more information was needed on non-pharmacological management (Table 2). Furthermore, when asked to describe their top issues in management of PAH-CHD, respondents mentioned issues such as pregnancy and birth control, iron deficiency, exercise, anticoagulation, dental/skin care, arrhythmias and role of venesection.
      There are currently no national protocols for the non-pharmacological management of PAH-CHD, however, recommendations are given in the ESC/ERS guidelines [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. Pregnancy is associated with substantial mortality in PAH patients [
      • Duarte A.G.
      • Thomas S.
      • Safdar Z.
      • Torres F.
      • Pacheco L.D.
      • Feldman J.
      • et al.
      Management of pulmonary arterial hypertension during pregnancy: a retrospective, multicenter experience.
      ] and therefore should be avoided [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. Most clinicians would recommend Mirena coil and progesterone-only preparations for contraception. As people with PAH are often iron-deficient, they should undergo regular monitoring of iron status and haemoglobin levels due to the potential impact of iron deficiency on exercise capacity and mortality [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. If iron replacement therapy is required it may need to be given intravenously due to poor oral absorption or intolerance [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Van De Bruaene A.
      • Delcroix M.
      • Pasquet A.
      • De Backer J.
      • De Pauw M.
      • Naeije R.
      • et al.
      Iron deficiency is associated with adverse outcome in Eisenmenger patients.
      ]. When a patient is diagnosed, a degree of realistic expectation management is required for activities related to daily living. It is often necessary for patients to adapt their lifestyle to avoid strenuous exercise and sometimes to alter their working patterns in order to still have the maximum quality of life. The current ESC/ERS guidelines recommend that patients should undertake supervised physical activity within the limits of symptoms [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. It is important for patients to avoid activity that causes syncope or severe breathlessness, but there is mounting evidence that ‘keeping fit’ is an important adjunct to pharmacological treatment [
      • Grunig E.
      • Lichtblau M.
      • Ehlken N.
      • Ghofrani H.A.
      • Reichenberger F.
      • Staehler G.
      • et al.
      Safety and efficacy of exercise training in various forms of pulmonary hypertension.
      ,
      • Mereles D.
      • Ehlken N.
      • Kreuscher S.
      • Ghofrani S.
      • Hoeper M.M.
      • Halank M.
      • et al.
      Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension.
      ]. Currently, it is not known which method of exercise rehabilitation should be used or the intensity and duration of exercise that should be applied [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. No study has yet determined whether exercise-training programs improve prognosis. An exercise regime will therefore need to be tailored to the individual patient, with realistic expectations.
      The most common arrhythmias seen in patients with PAH-CHD are atrial flutter (often relating to sites of previous incisions due to cardiac surgery) and ventricular tachycardia (resulting from postoperative chronic fibrosis, hypoxia or chronic volume loading) [
      • Olsson K.M.
      • Nickel N.P.
      • Tongers J.
      • Hoeper M.M.
      Atrial flutter and fibrillation in patients with pulmonary hypertension.
      ,
      • Rajdev A.
      • Garan H.
      • Biviano A.
      Arrhythmias in pulmonary arterial hypertension.
      ]. Both conditions require input from cardiac electrophysiologists and are poorly tolerated. The consensus view is that therapy involving high dose beta blockade should be avoided in patients with PAH, since it impairs their ability to generate an increased heart rate during exercise, impairs right ventricular function and can lead to symptoms of severe breathlessness [
      • Ministeri M.
      • Alonso-Gonzalez R.
      • Swan L.
      • Dimopoulos K.
      Common long-term complications of adult congenital heart disease: avoid falling in a H.E.A.P.
      ]. Venesection is generally not recommended in PAH-CHD since it renders the patient iron deficient and may actually be associated with an increased risk of stroke. It should only be performed, with isovolumetric fluid replacement, when there are symptoms of hyperviscosity [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. Unlike patients with idiopathic PAH, those with PAH-CHD are generally not anticoagulated, as they are prone to bleeding from dilated bronchial arteries and often have a low platelet count [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,

      Weaver H.A., Tulloh R.M.R. Thrombocytopenia in pulmonary hypertension, does it predict survival? 2013 [22.09.2016]. Available from: http://eurheartj.oxfordjournals.org/content/ehj/34/suppl_1/P318.full.pdf.

      ].
      General management measures are essential to improving both PAH-CHD outcomes and quality of life [
      • Dimopoulos K.
      • Wort S.J.
      • Gatzoulis M.A.
      Pulmonary hypertension related to congenital heart disease: a call for action.
      ]. The ESC/ERS guidelines offer clear guidance on non-pharmacological management of PAH, but at the current time no specific guidance is given for people with PAH-CHD and as not all general measures are applicable to this patient subgroup, specific guidelines are warranted.

      Palliative Care

      The current ESC/ERS guidelines recommend proactive advanced care planning with timely referral of PAH patients to palliative care services [
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ,
      • Galie N.
      • Humbert M.
      • Vachiery J.L.
      • Gibbs S.
      • Lang I.
      • Torbicki A.
      • 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).
      ]. A large proportion of physicians (82%) surveyed report having no formal palliative care service for PAH-CHD, but 81% of these feel that a service of this nature would be valuable to management (Table 7). To address this unmet need, it is recommended that each centre should have a palliative care service available, providing good quality end of life care. Of the 18% of physicians who do have a formal and appropriate palliative care service, all would consider referring a patient with a life expectancy of <6 months and 83% would also consider referral following repeated hospital admissions and/or deterioration to functional class IV. None of the respondents refer patients to palliative care at the point of diagnosis. There is, therefore, a gap in the provision of palliative care services and a need for guidance on the timing of referral to palliative care services [
      • Greutmann M.
      • Tobler D.
      • Colman J.M.
      • Greutmann-Yantiri M.
      • Librach S.L.
      • Kovacs A.H.
      Facilitators of and barriers to advance care planning in adult congenital heart disease.
      ,
      • Tobler D.
      • de Stoutz N.
      • Greutmann M.
      Supportive and palliative care for adults dying from congenital heart defect.
      ,
      • Tobler D.
      • Greutmann M.
      • Colman J.M.
      • Greutmann-Yantiri M.
      • Librach L.S.
      • Kovacs A.H.
      End-of-life care in hospitalized adults with complex congenital heart disease: care delayed, care denied.
      ]. Earlier referral to palliative care should be made when considering escalation of targeted vasodilator therapy.
      Table 7Palliative care in PAH-CHD patients.
      Aspects of palliative careRespondents who answered yes
      n/N%
      Do you currently have a formal palliative care service for PAH-CHD patients at your centre?
       Yes6/3318
       No27/3382
      When do you refer PAH-CHD patients to a palliative care service?
      Respondents could specify more than one time point and only respondents who reported having a formal palliative care service were able to answer this question.
       On diagnosis0/60
       After repeated hospitalisations5/683
       Upon deterioration to FC IV5/683
       Upon listing for transplantation0/60
       Life expectancy <6months6/6100
       Other3/650
      Do you think a palliative care service would be useful or valuable for the management of PAH-CHD patients in your practice?
      Only respondents who reported not having a formal palliative care service for PAH-CHD patients were able to answer this question.
       Yes22/2781
       No5/2719
      n/N: Number of respondents who selected this option/Total number of respondents who completed the question.
      Abbreviations: FC: functional class; PAH-CHD: pulmonary arterial hypertension associated with congenital heart disease.
      a Respondents could specify more than one time point and only respondents who reported having a formal palliative care service were able to answer this question.
      b Only respondents who reported not having a formal palliative care service for PAH-CHD patients were able to answer this question.

      Study Limitations

      There are several limitations to this study, which are related to the electronic nature of the survey. The survey was optional and therefore the physicians, who responded (13%), may have been more likely to be those who considered themselves to be knowledgeable in the field or who held strong opinions on the subject. There might have been potential selection bias, if the survey was too lengthy for busy clinicians. The demographic data, however, indicated that responses were obtained from a broad range of physicians including both PH specialists and general cardiologists. Furthermore, the low response rate was not unexpected as PAH is a rare disease (only 1000 people with PAH associated with CHD were seen by the UK PH service in 2014) [

      National Audit of Pulmonary Hypertension 2014 [21.12.2016]. Available from: http://content.digital.nhs.uk/catalogue/PUB17264/nati-pulm-hype-audi-2014-rep.pdf.

      ].
      The survey results could have been affected by recall bias. However, over a quarter of respondents (26.3%) stated that they were using a database to answer the survey questions. This is likely to increase the reliability of the results.

      Conclusions

      Our survey managed to capture both general cardiologists and physicians working in close cooperation with PH centres. It demonstrated that physicians who were seeing a large number of patients with Eisenmenger’s syndrome were more likely to initiate and manage patients with advanced PH therapy, and they were more likely to follow guidelines. In addition, the survey revealed a gap in the knowledge base for many therapies for patients with PAH-CHD. There might be other confounders, such as a patient or carer wish not to start therapy, but we did not see a reason why there might be a geographical variation in this but accept that there might be unrecognised alternative possibilities as to why the standard guidelines were not followed. This might even be more prevalent in a greater geographical area outside of this study, with the effect of cost containment, or other restrictions being in place.
      General cardiologists report the need for improved guidelines and increased access to specialist care for their patients with PAH-CHD. Efforts are needed to increase referral of such patients into PH services by developing referral criteria and to identify a best practice protocol for screening patients with CHD for the presence of PAH.

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