Exploring the patient perspective in pulmonary hypertension

Abstract

The global impacts of pulmonary hypertension (PH) were formally recognised in 1973 at the 1st World Health Organization meeting dedicated to primary pulmonary hypertension, held in Geneva. Investigations into disease pathogenesis and classification led to the development of numerous therapies over the ensuing decades. While the impacts of the disease have been lessened due to treatments, the symptoms and adverse effects of PH and its therapies on patients’ wellbeing and mental health remain significant. As such, there is a critical need to enhance understanding of the challenges patients face on a global scale with respect to care access, multidimensional patient support and advocacy. In addition, thoughtful analysis of the potential benefits and utilisation of mechanisms for the incorporation of patient-reported outcomes into diagnosis and treatment plans is needed. A summary of these areas is included here. We present a report of global surveys of patient and provider experiences and challenges regarding care access and discuss possible solutions. Also addressed is the current state of PH patient associations around the world. Potential ways to enhance patient associations and enable them to provide the utmost support are discussed. A summary of relevant patient-reported outcome measures to assess health-related quality of life in PH is presented, with suggestions regarding incorporation of these tools in patient care and research. Finally, information on how current global threats such as pandemics, climate change and armed conflict may impact PH patients is offered, along with insights as to how they may be mitigated with advanced contingency planning.

Shareable abstract

From the patient perspective, access to PH care globally remains a challenge in 2024. Support offered by patient associations and the use of patient-reported outcome measures are some examples of how the patient situation may be improved in a rapidly changing world. https://bit.ly/4cn67Hg

Introduction

The patient perspective of pulmonary hypertension (PH) has changed enormously since the start of the modern era of the World Symposium of Pulmonary Hypertension (WSPH) in 1998. During the 6th WSPH in 2018, the importance of the patient's perspective and experience living with pulmonary hypertension was more formally recognised [1]. While this perspective evolved from treatment options, it has since expanded to include multiple new components that still warrant further exploration and research.

In many countries the role of patients in PH has since evolved to see the development of patient associations and PH advocacy on a national and international scale, and to drive the development of supportive and rehabilitative care (which are integral components of palliative care). Patient associations are heterogeneous and it is important to define what makes a patient association. Having patients’ perspectives on their own healthcare heard by healthcare professionals through patient-reported outcome measures (PROMs) is a work in progress. Patients with PH need to access individualised supportive and rehabilitative care prescribed according to how they report their treatment goals, healthcare priorities and health-related quality of life (HRQoL) with PROMs. The incorporation of the patient perspective in new guidelines in 2022 [2, 3] marked a new step forward towards healthcare professionals working in partnership with patients.

Access to PH specialist care and support, including access to medication and surgical or catheter-based interventions such as transplantation, pulmonary thromboendarterectomy and balloon pulmonary angioplasty remains a huge challenge for many patients. This is particularly true for those in the Global South, which denotes a mix of political, geopolitical and economic commonalities between nations [4]. This challenge has become greater, since the beginning of the third decade of the 21st century has seen worsening effects of climate change, an increasing number of conflict zones and a global pandemic, all of which propel greater health inequalities to the detriment of PH patients and others with chronic conditions.

By exploring patients’ perspectives, we would like to drive better care for more patients globally before the next WSPH. Herein, we have focused on how PH care may be advanced in a changing world.

Pulmonary hypertension in 2024

The global picture

New insights into the patient's experience of and access to care throughout the world are emerging. Although PH mortality trends may have improved over the past two decades, there remain substantial differences in mortality and its temporal trends across different countries, with some deteriorating [5]. For example, in Africa there is a high burden of pulmonary vascular disease of diverse aetiologies and too few specialist facilities to manage even those who are diagnosed [6, 7]. In Kerala, India, left heart diseases were the cause of PH in 60% of patients [8]. The use of PH-specific drug therapies was also remarkably lower than in Global North countries. More specifically, the findings of an interim analysis of the Pulmonary Hypertension Global Patient Survey (PH GPS) (>3000 respondents) in December 2023 showed that of patients with idiopathic pulmonary arterial hypertension (PAH), 79.6% had never filled out a PROM, 79.5% had never taken part in a clinical research trial and 71.4% had not received genetic testing [9]. 75% of participants were from Europe and North America, while the remaining 25% were from South America, Africa, Asia and Oceania, which is not representative of the global distribution of patients. Overall, development of better healthcare for PH patients globally will depend upon high-quality information to make optimal use of local healthcare resources and develop specialist healthcare where possible through initiatives such as partnering of existing PH expert centres with those in development.

Patient and provider perspectives

To further understand the patient experience in PH, particularly in the Global South where access challenges are greater, this task force created separate surveys for patients/carers/advocates and healthcare professionals in PH. The survey was deemed exempt from formal institutional review board approval by the office of human research ethics at the University of North Carolina at Chapel Hill (Chapel Hill, NC, USA). This survey was given to a small group of individuals who reside in regions of Africa, South America, the Middle East, Asia and Oceania. They were selected by the task force for their broad understanding of the challenges faced by PH patients in their respective regions.

Responses were received from 11 individuals (seven patients/carers/advocates and four healthcare professionals). One major challenge noted was the lack of access to standard diagnostic right heart catheterisation (RHC). A provider from Africa stated “Most patients are diagnosed using a simplified algorithm with history, cardiac ultrasound and imaging; very few go to referral centres for RHC”. A patient in Africa said “The procedure is unavailable in most centres and states. When it is available, it is very expensive, and a lot of people can't afford to get it done”. Concern was also expressed from South America regarding the correctness and completeness of RHCs that are performed.

Another common theme among respondents was a lack of access to the full complement of PH medications in all areas. Furthermore, even access to the agents available in a particular region may be challenging. One patient highlighted the disparities in PAH therapy availability compared to other regions: “In terms of available treatments, we are well behind America and Europe. This limits options for patients”. Another related disparity even within their own region, stating, “State patients cannot get many of the PH medications, whereas some private patients have access depending on their medical insurance scheme. State patients’ access is limited and have to have generic where available”. A patient from Africa related the challenges in coverage for PH medications as such, “I have never used insurance or national healthcare scheme to pay for my medication, always out of pocket. From my knowledge and experience, I haven't found any insurer that is willing to cover my medications”.

Regarding the use of PROMs, providers identified lack of translated tools and lack of time in the clinical encounter as barriers to regular use. None of the four providers reported routine use of PROMs, and only one out of five patient/carer respondents had a PROM administered to them as part of PH care. This is consistent with the findings of the PH GPS noted earlier.

In addition, geographic factors affect care access in many of the regions surveyed. Both healthcare professionals and patients/carers surveyed estimated that 40–50% of patients across all the regions surveyed travel >1 h or >80 km each way to visit their PH provider. Most providers surveyed stated that they can provide visits via telehealth.

A provider from Africa summarised the general state of PH care on the continent as follows, “I believe PH is largely under-diagnosed or misdiagnosed due to limited resources both human and infrastructure to diagnose and treat this condition”. Another patient from Asia recapped the challenges in their region, with “Only a handful of PH specialists in such a populous country, under-treatment and mismanagement of PH by non-PH specialists, out of pocket spending on expensive medicines”. Collectively, the insights from this small global survey describe significant shortcomings in PH care in many regions of the world.

Patient support and rehabilitation

Introduction

The importance of maintaining the PH patient at the centre of all considerations with respect to screening, diagnosis, treatment, the PH multidisciplinary team (MDT), patient education and advocacy, the conduct of clinical trials, and other related components of care has been highlighted previously [1, 10]. Shared decision-making, in which a patient has access to the information and education that they need and want, while working with expert healthcare professionals to make the best choices about their care regarding diagnostics, therapy choices, treatment goals and priorities of care, should be the norm. Integral to fostering success with this approach is the way in which the MDT is structured and managed, as well as the level of patient support and education available. Furthermore, it is important to recognise the potential for holistic care, aimed at both the patient and carer, beyond the core medical treatment of the PH disease itself.

Multidisciplinary team PH support

The structure, skills and function required of an interprofessional PH MDT at a PH centre has been described in detail in recent guidelines [2, 3]. Functions of the MDT include providing clear verbal and written information for patients, shared decision-making, delivering supportive care and collaboration with advocacy groups. The MDT approach is essential to develop comprehensive treatment plans that not only manage the medical aspects of PH, but also support, maintain and rehabilitate physical wellbeing and mental health.

International PH guidelines

Expert recommendations with modifications to international guidelines, tailored to middle-to-low-income regions, where PH is underdiagnosed and there is limited access to diagnosis and treatment, were proposed in 2020 [11].

The 2022 European Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension [2, 3] updated all aspects of PH care and provided a detailed description of a PH centre and its multidisciplinary team, the value of patient empowerment and importance of patient associations. The use of HRQoL measures were recommended, for the first time in guidelines, as “may be considered” during the follow-up of PAH, but did not become a component of risk assessment in PAH or a treatment goal. A lay summary was published in 11 languages [12].

Quality indicators have been developed for the new guidelines [13] to evaluate access to PH centres, and the clinical quality of the management of PAH by analysing the degree of real-life adherence by clinical teams to clinical guideline recommendations. At a national level, quality indicators may reveal both local as well as country-specific achievements in access to care, its quality and areas for improvement.

The annual reports of the United Kingdom National Audit of Pulmonary Hypertension are so far unique examples of systematic analyses of such data [14] including PROMs. These serial reports have resulted in demonstrable improvements in many of the national standards of quality of care and have been able to provide quality assurance to patients of the service provided by their PH centre.

Seen from the patient perspective, the introduction of quality indicators to audit clinical practice may motivate healthcare professionals to improve patient care based on national and international comparisons and sharing their experiences. Importantly, PROMs and informing individuals about patient associations have been listed among recommended quality indicators [13]. This acknowledges the pivotal role that patient associations play in providing support to patients.

Supportive and rehabilitative care

This focuses on a personalised and whole-person approach to care that reflects individuals’ health and care needs, supports carers and encourages collaborations with the extended MDT and local agencies to deliver it effectively. This care extends to physical, psychological, social, spiritual and financial support where all domains are considered from the start of the patient's engagement with their MDT. This is when PROMs (discussed later) and the patient's own goals and priorities for rehabilitation of their health can be used to help the MDT understand and prioritise appropriate supportive care interventions jointly with the patient.

For example, the burden of living with PH is not just a physical one and anxiety and depression are common, so both patients and carers (given the emotional and physical demands of caregiving) may benefit from psychological support [15]. Managing symptoms, medication and its side-effects, as well as dealing with acute emotional reactions over loss of health, autonomy and income, and accessing care may have a significant impact on a patients’ and carers’ mental health and wellbeing. Grief over the loss of fellow patients may also be a significant burden. A whole-patient approach should incorporate regular assessments including PROMs encompassing psychological and emotional state as well as social needs, and referrals to supportive care as needed. Additionally, support should be extended to two special groups of people: the twin of a patient with heritable PAH who has not developed PAH but is at high risk; and patients with a diagnosis of PAH where the mean pulmonary arterial pressure is 21–24 mmHg where no PAH-specific treatment is licensed and individualised treatment is recommended [2, 3].

Another example is individually tailored physical activity. Exercise and rehabilitation are discussed further by Chin et al. [16]. New wearable external and implantable monitoring devices that capture heart rate, step count and haemodynamic variables may allow improved individualised exercise and activity monitoring and treatment, as well as earlier detection of clinical worsening. More research in clinical care and drug trials is needed to determine their role in PH [17, 18]. Patients may also benefit from individual nutritional counselling to help manage working towards or maintaining a healthy weight, fluid intake, attention to vitamin K intake if on warfarin, sodium restriction, responsible use or abstinence from stimulants or depressants such as caffeine and alcohol if needed, and potentially addressing some medication side-effects through food selection and timing of doses. A small study has raised the possibility of vitamin and mineral deficiencies in mild PAH [19], but more research is needed before suggesting a nutritional intervention.

Some aspects of supportive care are underused even by experienced PH physicians [20]. Palliative care spans the spectrum of supportive care through to end-of-life care. It is especially important for patients to understand this difference, as they may be more open to accepting palliative care if they do not associate it with impending clinical worsening or death. For a further discussion of palliative care refer to the article by Preston et al. [21]. At a final stage of progression of the disease, some patients may choose assisted dying, but it is not available in most countries.

In collaboration with patient associations, PH MDTs should be able to direct patients to advice about travelling with PH, overcoming mobility challenges, where to seek legal advice, completing forms for financial and social support, and to help navigate the administrative complexities associated with chronic illness and disability. Such an inclusive and multifaceted care approach is crucial for addressing most aspects of living with PH, and ensuring both patients and their carers are well supported.

eHealth support for patients and carers

PH patients and carers benefit from online resources that provide vetted and reliable medical information, knowledge sharing and lifestyle advice. Thanks to eHealth [22] and online tools, offering these services opens the door to greater worldwide access and support.

Many of these patient and carer communities have set up forums, message boards, e-support and social media accounts, where individuals can share their experiences, insights and advice. A new wave of support has also emerged through spontaneous informal social media groups and influencer blogs. Patient support websites and materials facilitated by pharmaceutical and healthcare companies, and working in cooperation with patient associations, are gaining prominence. A good example of such cooperation between the healthcare industry, patient associations, physicians and other healthcare professionals from all over the world is the elaboration of the PAH Patient Charter [23], which outlines the standards of holistic care which everyone with PAH should receive. To enhance accessibility, automated language translation features are now available on many digital platforms, enabling a more inclusive experience for individuals seeking support.

Misinformation and disinformation

False information about healthcare on social networks has been shown to influence patients’ healthcare choices [24]. While these different platforms offer valuable opportunities for sharing and peer-to-peer support, there is a concurrent risk of incorrect information being promulgated. In this realm of online support, some commenters and a lack of moderators pose challenges. Some PH influencers have consulting contracts with the healthcare industry, while patient support platforms established by the healthcare industry necessitate critical evaluation of their content. Diligent conflict-of-interest resolution and management is critical in this area for patients, advocates and providers alike.

Patients should exercise caution when navigating the internet or using artificial intelligence software, where the risk of disinformation and misinformation looms. They should instead prioritise information sourced from high-quality, trustworthy sources. When an online search was conducted to evaluate the truthfulness of false news articles, it increased the probability of believing them [25]. It must also be stressed that while these platforms are valuable, consulting healthcare providers remains essential for personalised guidance.

Digital knowledge platforms

Some examples of high-quality multilingual digital knowledge sharing for patients include the Alliance for Pulmonary Hypertension (AfPH), PHA Europe, and the Pulmonary Hypertension Association in the United States (PHA USA), who offer carefully curated and community-vetted resources aimed at an international PH community:

• 1) The Pulmonary Hypertension Knowledge Sharing Platform (PH-KSP) (www.allianceforpulmonaryhypertension.com) of the AfPH, launched on World Pulmonary Hypertension Day 2023, serves as a centralised repository of expert-curated resources, in various formats and languages, and includes dynamic sections on “news” and “events”, constantly updated and specifically tailored to the PH community. The PH-KSP is an open, inclusive and interactive space which anyone can access and contribute content. A dedicated section, entitled “Our webinars”, contains information about the AfPH knowledge-sharing web events.

• 2) The Bel Air Center (www.belaircenter.info) of PHA Europe is designed as a global virtual PH meeting point, open to PH patients, carers, healthcare professionals, industry partners and other PH stakeholders. Within the virtual conference centre, visitors can explore booths set up by patient associations and healthcare industry partners. These booths offer a range of information, including PH brochures, videos and additional supporting materials. Live events are hosted monthly in the conference room, and the virtual centre also features an art gallery displaying works by PH patients and healthcare professionals. The presentation room houses a variety of subtitled and dubbed PH presentations. In the recreational area, club members can interact through chat or informal video calls.

• 3) PHA USA maintains PHA Classroom (https://phassociation.org/patients/educationprograms/), a robust online learning centre for anyone who wants to learn about PH. The PHA Classroom houses numerous videos and resources providing education about topics such as understanding PH, living with PH, paediatric issues, insurance and treatment access and more. Resources are available in English and Spanish. The platform is updated regularly. PHA also maintains PHA Online University (https://phassociation.org/education-programs/medicalprofessionals/) which is aimed at medical professionals, but also accessible to patients and carers.

Virtual patient support across international borders in Europe

In Europe, cross-border patient care for rare diseases including PH has been developed by the European Commission (https://health.ec.europa.eu/european-reference-networks_en). The purpose of this European Reference Network for Rare Respiratory Diseases (ERN-LUNG) (https://ern-lung.eu) is to provide a centralised platform across borders to share knowledge and experiences with the objective of improving patients’ access to diagnosis, care and treatment. ERN-LUNG includes 33 representatives of patient associations.

ERN-LUNG enables patient management by teleconsultation. The Expert Advisory Board Online is a pan-European internet platform which allows patients and carers as well as nonexpert healthcare professionals to contact ERN teams for diagnostic advice when a rare disease such as PAH or chronic thromboembolic pulmonary hypertension (CTEPH) is suspected. The Clinical Patient Management System is a secure internet platform which shares anonymised clinical data and images for cross-border teleconsultations of particularly complex clinical cases. ERN centres can communicate to smooth the transition of patients between expert centres across Europe.

Support for patients in humanitarian emergencies

Displaced people

Extreme man-made and natural disasters, including those listed herein, may mean that people are displaced within their own country or across international borders, have nowhere to live, and have difficulty finding water, food, clothes, essential hygiene products and basic medical facilities [26]. Countries in the Global South are affected disproportionately as they have fragile healthcare and a higher propensity towards displacement of people, economic loss and poor mental health outcomes [27]. These people depend on humanitarian aid from governments and nongovernmental organisations (NGOs), often working in collaboration, but it is unlikely that they will always be able to access specialist medical care. NGOs include PH patient associations, and they should play a role in these situations as well. In humanitarian emergencies chronic disease management is often neglected [28]. PH patients who depend on a continuous supply of specialist medication including oxygen and access to expert PH medical care are particularly threatened by disrupted medication supplies and loss of contact with their PH centre. Collaboration between healthcare professionals, PH centres, patient associations and other humanitarian agencies may help to support patients in such challenging circumstances.

Climate change

Climate change presents a big health threat to everyone [29], and especially those who are vulnerable and disadvantaged such as those with underlying health conditions [30, 31]. The population at risk is additionally determined by geography, especially in areas with high levels of climate sensitive diseases, water stress and low food production [29]. For PH patients, particular examples include the exacerbation of respiratory symptoms from wildfire smoke and other air pollution, the spread of vector-borne and water-borne diseases following a flood or drought, and disruption of medication supplies and health services. Elevated temperature affects the stability of prostanoid infusions (>35°C reduces stability of thermostable preparations to 12 h).

Conflict zones

In conflict zones, healthcare is often negatively impacted and interrupted, and conflict-affected civilians may be forcibly displaced. Patients with chronic noncommunicable diseases (NCDs) have dramatically reduced access to healthcare facilities and treatment and suffer excess mortality [32, 33]. There may be destruction of life-saving medication supplies and disruption of supply chains with political unrest and changing government policies, and patients may resort to obtaining medication from unofficial sources with its attendant risks. eHealth [22] is finding an increasing role, but is predominantly provided ad hoc [34]. An example of managing PH patients in a conflict situation with a central role of patient associations collaborating with multiple stakeholders is narrated in the supplementary material.

Pandemics

eHealth has also expanded rapidly in response to the coronavirus disease 2019 pandemic in both the Global North and Global South [34]. This may offer opportunities for planning for future pandemics. An example of managing PH patient care with telemedicine in a pandemic is given in the supplementary material.

Suggestions for planning and managing PH in humanitarian emergencies

There is no structured guidance for managing NCDs in a humanitarian crisis [35], and no research or systematic collection of evidence for the medical care of PH patients. In the acute phase of a crisis, the focus will be on patients who already have a diagnosis of PH. Circumstances will depend on the preparedness of healthcare systems. In some situations, the internet may be shut down. Since an emergency response is better planned in advance, communication with patients and coordination of their care is central to preparedness. We propose the following suggestions expanding on those of PHA Europe [36], as follows.

1. Patients should ensure that they:

   • can self-manage their PH according to World Health Organization recommendations [37];
   • maintain a supply of prescription medications in collaboration with healthcare professionals and pharmacies;
   • can use a mobile phone and/or computer to connect to telemedicine consultations with healthcare professionals;
   • know when and where to seek unplanned medical help;
   • keep an up-to-date dossier of their medical summaries which is ready to take with them if they must move at short notice.
2. Role of healthcare professionals and patient associations includes:

   • encouraging patients and carers to be prepared;
   • in an acute humanitarian emergency, ensuring continuity of care through an integrated approach of local health services with PH centres, and ensuring prioritisation of medication supplies and care for high-risk patients, including those receiving prostanoid infusions and oxygen;
   • facilitating a multistakeholder approach for PH patients in preparation for, and during an emergency including partnerships with healthcare systems and agencies, healthcare professionals and NGOs, including other patient associations internationally. This includes developing cross-border contacts and planning for continuity of care in case of migration of PH patients;
   • developing or maintaining international eHealth platforms for telemedicine;
   • patient associations and healthcare professionals maintaining a list of contacts of their patients, flagging those who are at high risk receiving prostacyclin infusions and/or continuous oxygen, and carer members in accordance with region-specific privacy laws such as the European Union (EU) General Data Protection Regulation.

Patient associations for support and advocacy

The first PH support groups emerged in the 1990s, and since then the PH world patient support network has grown to include ∼90 patient associations active at national level (some countries have more than one), and at least four umbrella organisations (two in Europe and two in Latin America). Patients seeking support can explore a variety of avenues, beginning with patient associations, which offer comprehensive resources and community connections at local, regional and global levels. It is worth noting that in many countries, the absence of local patient support groups poses a significant challenge, although this obstacle can be mitigated, at least in part, by connecting with other patient associations online.

Over time, patient associations have become more structured and professional, expanding their roles to encompass global awareness and advocacy initiatives (table 1). Since its inception in 2012, World Pulmonary Hypertension Day (5 May) has become a pivotal annual event, drawing the active participation of numerous PH patient associations and stakeholders worldwide. With the participation of >80 patient associations, visuals with the same global branding, dedicated webpage and many posts available in numerous languages on social media channels, millions of people are reached and informed about pulmonary hypertension. As 29 February, Rare Disease Day, is a rare occurrence, the PH community worldwide flags this day to raise awareness about PH. In non-leap years, Rare Disease Day is observed on 28 February. Many patient associations report anecdotally that thanks to their higher visibility around these days, the number of calls they receive about potential cases of pulmonary hypertension increases exponentially. November is Pulmonary Hypertension Awareness Month, which is starting to become an important activity with global reach for raising awareness. As part of it, 8 November is dedicated solely to PH group 4 as CTEPH Awareness Day.

TABLE 1.

Achievements and ongoing initiatives of pulmonary hypertension (PH) patient associations

Global Awareness campaigns	• World Pulmonary Hypertension Day (5 May) since 2012
	• Pulmonary Hypertension Awareness Month (November)
	• CTEPH Awareness Day (8 November)
Advocacy campaigns	• EP event Call to Action on Unmet Needs of Patients with Pulmonary Hypertension 2022
	• EP event on transplant 2016
	• Online EP event Accelerating EU Research for Rare Diseases – the Case of Pulmonary Hypertension
Co-authorships in scientific papers	• ESC/ERS guidelines on PH 2022
	• Lay summary of ESC/ERS guidelines 2022
	• ERS statement on CTEPH
	• WSPH 2018 and 2024
	• Several journals including, but not limited to, Chest, European Heart Journal and Pulmonary Circulation
Scientific advice	• EMA
	• US FDA
Education of healthcare professionals	• PHA (USA) Online University
International conferences	• PHA (USA) bi-annual
	• PHAE APHEC
PH expert centre accreditation system (PHCCs)	• PHA
Patient education	• All patient associations
PH online libraries/knowledge-sharing platforms	• PH-KSP
	• Bel Air Center
Affiliations within scientific societies	• ESC forum
	• ESC workstream on emotional wellbeing
	• ERS working group on rare lung diseases
	• ERS CRC PHAROS
	• ERS task force on BPA
	• ESOT member of education committee
	• ESOT member of congress programme committee and chair of 2023 congress
	• ESOT working group on rehabilitation
	• ELF patient organisation network
	• ELF PH PAG
	• ERN-LUNG PAGs, medical steering committee
	• ERN-LUNG project management
Roles within public health NGOs	• EURORDIS (Rare2030)
	• EPF
EU institutions	• MEP lung health group
Research institutes	• PVRI Innovative Drug Development Initiative workstream on patient engagement and empowerment
Industry	• Advisory boards
	• Patient councils
	• Consulting agreements on specific projects
Speaking engagements	• National and international scientific societies, industry events, academic events, patient association events, national service club events. Examples including but not limited to: NORD, US FDA, PHA (USA)

PHCC: Pulmonary Hypertension Care Centres; NGO: nongovernment organisation; EU: European Union; CTEPH: chronic thromboembolic pulmonary hypertension; EP: European Parliament; ESC: European Society of Cardiology; ERS: European Respiratory Society; WSPH: World Symposium of Pulmonary Hypertension; EMA: European Medicines Agency; US FDA: United States Food and Drug Administration; PHA: Pulmonary Hypertension Association; PHAE: Pulmonary Hypertension Association of Europe; APHEC: Associations of Pulmonary Hypertension of European Countries; PH-KSP: Pulmonary Hypertension Knowledge Sharing Platform; CRC: Clinical Research Collaboration; PHAROS: Pulmonary Hypertension mAnagement acROSs Europe; BPA: balloon pulmonary angioplasty; ESOT: European Society of Organ Transplantation; ELF: European Lung Foundation; PAG: patient advocacy group; ERN-LUNG: European Reference Network for Rare Respiratory Diseases; EURORDIS: European Organization for Rare Diseases; EPF: European Patients Forum; MEP: Member of European Parliament; PVRI: Pulmonary Vascular Research Institute; NORD: National Association of Rare Disease.

Patient association advocacy efforts have proven successful both nationally and internationally. Patient associations are in active dialogue with local policy-makers, decision-makers, health technology assessment bodies and payers about access to treatments and medications, recognition of PAH and CTEPH as rare diseases by governments/health agencies/policy-makers, reimbursement and drug availability issues. These local endeavours are reinforced and underpinned by international and global advocacy activities. Patient representatives are increasingly playing vital roles in large global scientific societies, including their programme committees. In a groundbreaking move, two patient representatives were appropriately included among the authors of the 2022 European clinical guidelines on PH. Patients have also started to be invited to take part in steering committees for clinical trials.

Patient associations are actively collaborating with EU institutions, engaging with members of the European Parliament (MEPs), MEP groups and the United States Congress. To have a louder voice, PH patient associations sometimes join ad hoc working groups to submit a joint statement (e.g. thematic network on improving organ donation and transplantation in the EU 2019 [38]) or issue a position paper (e.g. EU pharmaceutical legislation [39], EU Health Data Space [40]). Their involvement extends to regulatory authorities such as the European Medicines Agency (EMA) and the United States Food and Drug Administration, as well as healthcare industry activities, including participation in clinical research and advisory boards. This multifaceted engagement underscores the growing influence of patients in shaping guidelines, policies and research initiatives across various spheres.

There are additional ways patient associations are contributing to research: 1) in many countries, special patient association foundations are established and the funds collected are donated to research institutes as unrestricted grants; 2) involving politicians to keep pulmonary hypertension and rare and chronic diseases on the top of the agenda has been used to encourage research funding from public sources; with the participation of MEPs and the representative of the Directorate-General for Research and Innovation (European Commission), an online political event was organised on how to accelerate EU research in rare diseases, using PH as an example; and 3) undertaking their own research such as that by PHA UK (www.phauk.org/research/pha-uk-led-research/).

While the current global patient support landscape is extensive and diverse (figure 1), the levels of support offered by patient associations varies significantly. This discrepancy is influenced by factors such as the financial position of patient associations, the availability of volunteers/staff, and the geographical, cultural and political contexts. Not all patient associations have a scientific committee or collaborate closely with PH experts, potentially impacting the accuracy and appropriateness of the information they publish.

FIGURE 1.

Distribution of patient associations throughout the world with key organisation attributes noted where known. Countries with a patient association are shaded. Patient associations not part of a larger umbrella organisation by primary membership are listed individually. For a comprehensive international listing of patient associations that is updated over time, refer to: https://phassociation.org/international/. Other organisations and foundations around the world that do not meet the formal criteria of a patient association have also developed research and advocacy efforts to support the pulmonary hypertension (PH) cause. An exhaustive list of all is beyond the scope of this work, but recognition of their presence and impact is imperative. HTAPQ: Hypertension Artérielle Pulmonaire Québec; PHA: Pulmonary Hypertension Association.

Since there is no international standard for designating or accrediting PH patient associations, it may be difficult for patients and carers to verify whether a patient association is officially registered, possesses nonprofit status, engages responsibly with industry, makes their financial statements publicly available, has transparent governance practices and implements conflict of interest policies before placing their trust in them. Compliance with data privacy laws remains an ongoing concern.

These considerations do not diminish the inherent value that patient support networks provide, but highlight the need for greater transparency, accountability and diligence in the patient support ecosystem.

Challenges of keeping patient associations operational

Financial

Ensuring the sustainability of patient associations presents many challenges, one of the most important of which is securing sustainable and consistent funding. Reliance on membership numbers, donations, legacies, grants and sponsorship from healthcare companies which may enter and exit the space can make planning for long-term financial stability challenging.

Patient associations vary in their charging of membership fees. No matter how nominal, membership fees may foster a sense of commitment and participation with an organisation. Fees can be waived in cases of financial hardship. In the case of industry support, clear guidelines and conflict of interest policies are vital to ensure transparency, integrity and ethical collaboration, preserving the interests and trust of all parties involved. In addition, restrictive national laws and internal company policies add layers of complexity to how and what industry partners may support.

The optimal financial structure depends on individual countries and may include nonprofit organisations, not-for-profit organisations and charities, hereafter referred to as nonprofits. In some countries, for example, support for nonprofits can flow from government tax structures.

Operational considerations

Attracting and retaining dedicated volunteers and staff members is essential for the continuity of patient associations. Balancing the needs of volunteers, who themselves often have health issues and/or limited availability, with the demands of organisational goals can be a delicate task. Maintaining relevance and engagement of the patient community is crucial in the face of rapidly advancing medical knowledge and technologies.

While many patient associations and patients rely on social media for raising awareness, the ability of an organisation to reach patients may be compromised when social media companies change algorithms, which impacts organic and paid reach of intended audiences. As social media companies rise and fall in popularity, challenges arise in capturing the younger generations who may largely reject established platforms, which they see as outdated.

Extreme situations increase the obstacles to bringing patients together for face-to-face events and fundraisers, as well as providing treatment and support.

Suggestions for constitution of PH patient associations

Criteria for professional organisations including patient associations involved in EMA activities have been described [41]. While geographical, political, legal and cultural differences may shape how nonprofits operate and are structured, a definition of the minimum requirements that PH patient associations need to meet is necessary considering the PH guidelines which provide recommendations for collaboration with them.

We suggest that patient associations:

• 1) Be patient- and carer-focused. Patients and carers should represent a majority of members on the governing body, which is elected by the members. Statements and opinions of the patient associations should reflect the views and opinions of its members.

• 2) Aim to raise awareness of PH, provide information and support for patients and carers including peer-to-peer support and networking opportunities, advocate for patients’ rights, and interact with healthcare professionals.

• 3) Operate as a legally registered entity, as a designated nonprofit association.

• 4) Operate in a transparent way, including:

  • implementation and publication of a data-privacy policy;
  • implementation and publication of a conflict-of-interest policy;
  • publication of conflicts of interest of its staff and board members;
  • publication of its organisational structure;
  • publication of contact details of the association and its senior staff;
  • publication of audited financial reports and disclosure of its sources of funding both public and private by providing the name of the bodies and their individual financial contribution;
  • publication of an annual activity report on the use of funds;
  • publication of an annual summary of accomplishments including awareness campaigns, advocacy activity, patient services and any related activities;
  • publication of guidelines for fostering relations with the healthcare industry.

• 5) Have a scientific committee, advisory board or consultant(s) comprised of PH experts (healthcare professionals who are specialists in PH and/or work at a PH centre).

• 6) Should publicly declare consultants/employees who work for remuneration.

• 7) Collaborate and cooperate with scientific communities and other patient associations.

• 8) Have a website, as well as regular communications and publications for its members.

This list is not exhaustive and may need to be expanded according to local requirements. For patient associations starting up it is understood that all these aims may not be achieved from the outset.

Patient-reported outcome measures

For 98% of PH patients, poor HRQoL impacts their life, mainly in the physical functioning domain, but also in the psychological domain [42], and improvement in HRQoL is what they most hope to gain from treatment [43]. HRQoL is the impact that a person's state of health has on their overall life [44]. Patients are usually the best judge of how they feel. PROMs describe patients’ perspectives of their health and HRQoL [45, 46], complement other clinical information and may improve clinical management [47]. PROMs are free from the influence of human choice, judgement and motivation of healthcare professionals or other individuals, in contrast to conventional clinician-reported outcomes, which can be influenced by these [45, 48]. Disease-specific instruments provide a detailed picture of a patient's assessment of their own health, and tend to be valid, reliable and sensitive. Generic PROMs assess overall health and its effect on the ability to function and enjoy life [44]. The value of incorporating the patient's perspective in PH management was emphasised during the 6th WSPH and underscored the necessity of empowering and actively engaging patients in every facet of their healthcare journey [1].

PH-specific PROMs

PH-specific PROMs have been developed for PAH and CTEPH, and this discussion of PROMs refers only to these forms of PH. PROMs commonly used in adults with PAH and CTEPH are described in figure 2. There are no PH-specific PROMs for children or their proxies, but they need to be developed if possible. PROMs need to be chosen to best match their purpose and situation [49, 79]. Patient adherence to completing PROMs depends on patient engagement and is affected by completion times, which are shorter when electronic means are used [50].

FIGURE 2.

Patient-reported outcome measures (PROMs): potential value and what they measure. Included is a table summary of commonly used PROMs in routine clinical care and research for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) [2, 3, 49–59]. HRQoL: health-related quality of life; PH: pulmonary hypertension; MCID: minimal clinically important difference; CAMPHOR: Cambridge Pulmonary Hypertension Outcome Review; PAH-SYMPACT: Pulmonary Arterial Hypertension – Symptoms and Impact Questionnaire; PAHSIS: Pulmonary Arterial Hypertension Symptom and Interference Scale; EQ-5D: EuroQol 5-dimension; SF-36: 36-Item Short-Form Health Survey questionnaire; 6MWD: 6-min walk distance; FC: functional class; BNP: brain natriuretic peptide, PVR: pulmonary vascular resistance; D_LCO: diffusion capacity of the lung for carbon monoxide. ^#: PAH and CTEPH.

Rationale for PROMs in routine clinical care

Routine systematic use of PROMs in clinical practice (figure 2) may lead to better communication and decision-making to guide clinical and supportive care between healthcare professionals, patients and carers, and improve patient management and their satisfaction with care [51–55]. This depends on both healthcare professionals and patients being engaged in PROM completion and data collection, understanding its benefits, and healthcare professionals responding to patient preferences and needs derived from PROMs [56].

PROMs not only highlight the issues that patients experience, but also those that they might not have thought to raise with healthcare professionals if they were unaware of their relevance [57]. Completion of a PROM may in itself contribute to helping patients to feel cared for [57]. Better health outcomes have been reported where interventions are targeted at risk factors identified by PROMs such as depression [58]. PROMs may assist patients’ self-management of their disease [80].

Serial PROM assessments during the follow-up of patients with PH may be helpfully added to traditional clinical measurements of disease stability and prognosis [2, 3, 60]. These include the evolution of quality of life and disability as well as symptoms, emotional and physical functioning. Such information may be helpful in discussing prognosis, changes to treatment and supportive care, advanced care planning and end-of-life care.

There are no published data about the value of systematic PROM use in PH patients in the Global South, and no such trials have been conducted in PH patients in that region. While it may be inferred that PROMs in the Global South may improve communication, decision-making and patient satisfaction, without current data it is unknown whether PROMs result in better health in all cultural and geographical contexts. PROMs may serve to better facilitate communication between patients and healthcare professionals, particularly when there are cultural factors that lead to real or perceived communication challenges between them [81].

Using PROMs in routine clinical practice

PROMs are not firmly established in routine PH clinical care. Between 2011 and 2022, quality-of-life measurement in 20 high-volume PAH centres in Europe, each representing a different country, rose from 20% to 65% of centres [82].

In a survey in 2021–2022 of 30 PH centres in 15 countries in ERN-LUNG, half of the centres administered PROMs during routine clinical practice (personal communication, ERN-LUNG, Frankfurt am Main, Germany). These PH centres used four different PROM tools with varying frequency of administration from every patient visit to less than once per year. The barriers to using PROMs were cited as lack of available time, lack of experience using PROMs, lack of ability of electronic patient records to record PROMs, different language availability of some PROMs, patient adherence to completing PROMs, cost of the license to use some PROMs, inadequate validation of some PROMs and lack of conviction of physicians about their value in clinical care. Nevertheless, the use of PROMs in clinical practice has proven to be both feasible and beneficial, adding significant value to clinical care [83] and providing quality assurance to patients of the level of service their local PH centre provides [84].

Healthcare professionals need to acquire expertise on using PROMs and interpreting the data [85]. This requires significant initial training of healthcare professionals and patients who are unfamiliar with using PROMs (online courses for healthcare professionals and PH patients are planned). This includes feeding back PROM scores to patients [85]. Streamlining the integration of PROMs data collection with electronic patient records is also important. PROMs may raise unrealistic expectations of care and disrupt the healthcare professional–patient relationship [86].

In a systematic review of PROMs, it was suggested that emPHasis-10 and CAMPHOR were well suited for clinical use [59]. The Pulmonary Arterial Hypertension – Symptoms and Impact Questionnaire (PAH-SYMPACT) has also been used successfully in clinical practice albeit with fewer reports than emPHasis-10 and CAMPHOR [83]. While emPHasis-10 and CAMPHOR have important differences (figure 2), emPHasis-10 scores correlate well with CAMPHOR domain scores [60]. The optimal frequency of completing a PROM has not been determined and may differ where PROMs are used to accompany clinical encounters or are used for self-management of disease. Agreement between healthcare professional and patient according to clinical need to complete PROMs is likely to support adherence to PROM completion.

Suggestions for PROMs in clinical practice

1. Healthcare professionals should ensure that they are trained to make optimal use of PROMs in routine clinical practice.

2. PROMs should be strongly considered during the routine clinical care of patients to improve communication between healthcare professionals and patients and carers; to inform the PH MDT in providing individualised clinical care, supportive care, as a structured basis for shared decision-making, and serial monitoring of change in health; and to improve clinical performance through quality assessment.

3. Among PH-specific PROMs, CAMPHOR and emPHasis-10 are appropriately suited for routine clinical use, with emPHasis-10 being more conducive due its brevity. PAH-SYMPACT may also be used.

4. The use of electronic PROMs (ePROMs) is encouraged to improve convenience, reduce the time to complete PROMs, and provide the capability of setting digital reminders.

5. The frequency of administration of PROMs and their ad hoc use for routine clinical care should be determined by patients along with their PH team. It is preferred, but not evidenced to complete a PROM at least once per annum.

6. The value of inclusion of PROMs in comprehensive risk assessment and hence requires testing as a treatment goal for PAH patients.

PROMs in clinical trials

The incorporation of PROMs as clinical trial end-points is well established in PH. PROMs are unique in clinical trials in capturing patients’ perspectives of symptoms and their impact, HRQoL and the effect of treatments, although no PH-specific PROM captures patients’ experiences in their entirety [87]. The choice of the optimal PROM(s) for a trial needs to be based upon patient selection, international guidance on PROM selection in clinical trials [88], the aim of the trial, the expected properties and side-effects of the planned intervention, the PROM's acceptance by regulatory agencies, and other trial end-points. PROMs must also ensure cultural equivalence of measures across the linguistic/cultural groups recruited into the trial. This may be aided by having a member on trial steering committees with PROM expertise [85]. PROMs commonly used in current PH trials, including CAMPHOR, emPHasis-10, PAH-SYMPACT and Living with PH, differ from each other in the domains covered, the statements which participants score, the recall period and the number of questions (figure 2), which influences which PROMs are chosen.

PROM results need to be presented in a clinically relevant format to understand the implications of the findings [89], and this may require expert advice. Patients not taking part in a trial may use the results to judge the likely benefits of a treatment in their own case [44]. Based on guidance in cardiovascular disease, the reporting of PROMs as end-points is more clinically intuitive when within-patient change is reported as the number of patients needed to be treated to improve the PROM significantly when comparing one treatment with another, rather than only the difference in mean scores [90].

Patients in clinical trial design and conduct

PROMs are just one aspect of a broader role of patient involvement in clinical trials aimed at improving the quality of clinical care [91]. Patient involvement includes shared leadership, collaboration on planning, designing and conducting clinical trials, enabling expert “trialist” patients to communicate the results in a practical and useful manner to other patients, participating in drug licensing, drug approvals, health technology assessments, supporting reimbursement, and contributing to post-marketing surveillance [90] (figure 2). Facilitators of patient engagement and resources to ensure active engagement of patient partners have been summarised [90].

Patient and public involvement with trialists can benefit from working closely together during the entire clinical trial lifecycle, as evidenced by success in areas such as oncology, mental health and diabetes, where significant improvement in recruitment occurred when patients were involved [92]. This cooperation is yet to be fully adopted in PH trials, despite previous recommendations [1].

Suggestions for PH clinical trials

• 1) Patients should be actively involved as consultants in clinical trials, including as members of trial steering committees, for the entire lifecycle of each trial.

• 2) PROMs should be included as end-points in clinical trials. Patients should take part in the selection of PROMs for individual trials.

• 3) Patients should lead in the development of a lay summary of trial results including PROMs.

• 4) Clinical trial steering committees should consider including an expert on PROM selection, analysis, interpretation and communication.

• 5) To obtain the optimal value from PROMs in clinical trials, their application, data analysis, interpretation and reporting requires further consideration and guidance.

Care access and delivery: challenges, opportunities and priorities

Suboptimal access to expert and comprehensive care in PH is driven by health disparities and inequalities related to patient socioeconomic status (SES) and social determinants of health (SDH) [93]. These are tied to economic, geographical, environmental, political, racial, ethnic and cultural factors. Other factors such as gender bias and intersectionality (i.e. race and gender attribute combinations) are also important considerations [94–96]. The specific challenges can vary between and within countries, but have the common consequence of the patient being under-resourced or disadvantaged in some way that prevents them from getting an expeditious diagnosis, impairs or prevents access to PH centres and PAH treatments, including surgery, and leads to poor outcomes [97, 98]. There have been recent consensus statements on the potential impacts of healthcare disparities and inequalities in PAH, as well as calls to action for research to better understand their scope and impacts in the disease [99].

PAH presents a burden to the patient not only from symptoms and lifestyle impacts, but also economically. Although significant advances in the number of therapies for PAH have been realised, the cost of treatment remains high. The high cost of many standard-of-care PAH/CTEPH medications and surgical procedures limits access even among insured patients in the Global North and severely restricts availability in the Global South [100]. The distribution of aetiologies of PH (and PAH) varies considerably between the Global North and Global South, owing to both socioeconomic and geographical factors [101]. Diagnostic ability to properly characterise cardiopulmonary haemodynamics and classify PH is critical, but restricted in the Global South, as access to RHC and other advanced diagnostics is not ubiquitous [102].

Understanding the drivers of differences in PAH outcomes among racial and ethnic groups remains a challenge. To understand this, information regarding SDH and/or SES needs to be obtained when studying different patient groups in clinical trials or patient registries. Data including, but not limited to income, poverty level, level of education achieved and geographical location of residence can help to parse out the potential genetic/biological effects of race/ethnicity versus extrinsic factors such as SES and SDH, although it is recognised that these are undeniably linked to race/ethnicity in certain contexts [103]. The United States-based Pulmonary Hypertension Association Registry is one such example where data on SDH are collected. This has successfully facilitated the study of the impacts of SDH on outcomes among Hispanic patients with PAH [104].

While it is recognised that implementation of PROMs is an element of the patient empowerment strategy, the importance placed on patient empowerment, as well as the SES and SDH of patients, may significantly differ between and within continents and countries. Knowledge of the practical problems facing a patient with unexplained dyspnoea suspected or confirmed to be due to progressive forms of PH in various economic and geopolitical settings has not been researched systematically. Initial attention was directed towards differences in approval status of PAH drugs. Formal drug approval does not necessarily translate into practical availability. Beyond costs, availability can be limited by country-specific insurance and reimbursement policies, and systems controlling drug prescriptions and their dispensing, even in highly developed nations. Pharmaceutical companies might also choose not to market a certain drug in a particular country, thereby reducing the availability of drugs in certain regions. Understanding the global and country-/region-specific problems faced by the patient is crucial for ongoing improvement and revision of existing PROMs, which may not mean the same in different economic, social, cultural and political settings.

Gender and reproductive health access in PAH

It has been noted previously that PAH predominantly affects women. Despite advances in PH management, mortality related to pregnancy remains high [103, 105]. PH guidelines have consistently advised that pregnancy presents increased risk to women with PAH and have recommended early pregnancy termination in high-risk patients [21, 106]. Given this, it is conceivable that in regions where legal termination of pregnancy is unavailable, maternal mortality may increase in patients with PAH. Recent loss of national constitutionally protected legal pregnancy termination in the United States has led to differential access throughout the country. This access disparity is further exacerbated in disadvantaged people where SES and SDH limit ability to travel to states where pregnancy termination is still legally accessible. Calls to action highlighting the scope of the problem and needed solutions have been published [107].

Conclusion and future perspectives

In 2024 many people around the world who likely have PH are struggling to obtain a diagnosis and appropriate specialist treatment with holistic supportive and rehabilitative care to obtain the best outcomes. As the medical care of PH patients becomes more complex, it will be ever more important to understand patients’ perspectives of their illness, and in the absence of a cure, whether their own targets that they wish to achieve with treatment are being realised.

Patient associations have an important role to play driving advocacy to achieve better opportunities for patients. Momentous scientific advances which have changed the perspectives of PH patients continue to be made and it is imperative that patients participate in developing and designing new trials. Patients are ultimately the most directly affected by the disease, hence their involvement in all facets of drug and treatment developments, as well as related policy-making, is vital. The world of PH needs to evolve with patients, carers, patient associations, healthcare professionals, researchers, academic institutions, the healthcare industry, politicians, governments and NGOs working together in a global partnership. The multiple factors informing and affecting the patient and carer perspective on living with PH (figure 3) warrant research and/or quality improvement to optimise the patient experience.

FIGURE 3.

Overview of various factors and perspectives affecting and informing the pulmonary hypertension patient's experience of living with the disease. PROMs: patient-reported outcome measures.

Since most PH publications refer to activities in the Global North, we encourage readers and patient associations in the Global South to inform our task force of their advocacy activities via the corresponding author so that we can proceed in understanding the evolving global picture of PH.

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