Exploring the patient perspective in pulmonary hypertension

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.

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.

Support for patients in humanitarian emergencies

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.

Challenges of keeping patient associations operational

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.

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].

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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.

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].

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].