Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease,1,2 with estimates of incidence in adults of 5–10 subjects per million/year and 15–60 adult subjects per million.3 In population-based registries of PAH, incidence and prevalence rates range between 2.0 and 7.6, and 5.9 and 26 subjects per million of the population/year, respectively.4,5 Despite advances in the treatment of PAH,6–10 there is still a substantial proportion of misdiagnosed patients and inappropriate treatment of PAH in clinical practice.11–13 Although consensus documents and clinical practice guidelines for the diagnosis and treatment of pulmonary hypertension have been published,3,7,14,15 different studies have confirmed the lack of consistency between recommendations and clinical practice.12,16,17

It is estimated that there are 30–35 active PAH units in Spain (data from the REHAP registry).18 At national level, there is a great variability regarding the organizational models for the care of PAH patients. The knowledge of the characteristics and resources available in the units involved in the healthcare of PAH patients is important as a starting point to design strategies for improvement. The primary objective of the study was to analyze the units dedicated to the clinical management of patients with PAH, the available resources, and the characteristics of current clinical practice in the management of PAH, as well as to identify the needs and areas of improvement in the care of these patients in Spain. Secondary objectives were to collect information on the structure of PAH units, to determine the clinical profile of patients seen in these units, and to evaluate the knowledge and level of adherence to the current guidelines for the management of patients with PAH.

A cross-sectional and multicenter study based on a survey was designed for the collection of data.

The questionnaire was developed by a scientific board composed of a cardiologist and a pulmonologist, with considerable experience in the care of patients with PAH. The questionnaire consisted of 28 items, grouped into four main sections: (a) structure of the pulmonary hypertension unit (11 items and 9 subitems); (b) care of the patient with PAH (7 items and 4 subitems); (c) available resources and care requirements for PAH adult patients (6 items); and (d) adherence to current clinical practice guidelines (4 items and 2 subitems).

Participants in the study were mainly cardiologists and pulmonologists along with other specialists working in Spanish hospitals involved in the care of adult patients with PAH.

The fieldwork was carried out from January 30th to July 1st, 2017. The participants were mostly recruited among members of the Pulmonary Arterial Hypertension Spanish Registry (REHAP)18 through invitations sent by e-mail. Also, cardiologists and pulmonologists who met the inclusion criteria, registered in the Medynet database (a website platform for healthcare professionals), were invited to participate in the study. Physicians who, after receiving information of the study, accepted to participate were provided with the microsite URL where the questionnaire was lodged and the user's password. Participation in the study was anonymous, voluntary, and unpaid.

Descriptive statistics included frequencies and percentages for categorical variables and mean±standard deviation for continuous variables. Data were analyzed using the SAS statistical program (Statistical Analysis Systems, SAS Institute, Cary, NC, United States) version 9.1.3 for Windows.

The professional profile of physicians who participated in the study supports the relevance of the data obtained. Taking into account that the REHAP registry (Spanish Registry of Patients with Pulmonary Artery Hypertension) involves the participation of 38 hospitals, the sample size of this survey would cover more than 50% of the PAH units in the country. A high percentage of participants had an experience of more than 11 years and treated a considerable number of PAH patients annually, were chiefs of service, leaders or coordinators of a PH unit and were contributing members of the REHAP Spanish registry of Pulmonary Hypertension.18

On the other hand, in a multinational study with a similar design, assessing the extent to which PAH experts shared common practice patterns in alignment with published recommendations,13 survey respondents were from 25 countries and 6 continents. The study concluded that in general practice patterns among PAH experts diverge from consensus recommendations, suggesting that opportunity may exist to improve care quality.

Conversely, the results obtained in the present study suggest that a vast majority of PAH units members of the REHAP group that participated in this survey, adhere the ESC/ERS guidelines of pulmonary hypertension in clinical practice, although some opportunities for improvement were also identified.

Regarding the structure of the units for the management of patients with PAH, 75% of the respondents’ hospitals had a PAH unit, however their role as a reference center was limited. Although not all PH units have hospital beds available for PAH patients, critical care units were available in 50% of the centers for the more severe patients. Another aspect to be highlighted is that only 60% of PAH units held specific multidisciplinary meetings, mostly on a monthly basis. Given the complexity of the management of patients with PAH, it seems reasonable to improve this aspect. In fact, an adequate diagnosis and the multifactorial approach to assess the prognosis of the disease in individual subjects are key aspects in the care of patients with PAH and require experience, technical training and multidisciplinary care to achieve optimal outcomes.19,20

Although 75% of units participated in registries of pulmonary hypertension, mainly at national level, the research activity was scarce with a median participation in collaborative research projects in the last 5 years of only 1.5 [range 1–25]. It is necessary to implement strategies and to provide resources aiming to increase the scientific research capacity of PAH units and to enhance the visibility and impact of these activities at national and international levels.

More than half of the respondents treated patients in functional class III/IV, which indicates the severity of the disease and the marked limitation of physical activity of these patients. The survey has revealed some aspects that deserve attention, such as the variable percentage of patients with PAH who receive health education, the scant attention paid to quality of life assessments, and the frequent lack of access to support from social workers or psychologists’. Several studies have shown the impact of the disease on different domains of the patient's quality of life, insisting on the need of assessing the quality of life as an important outcome associated with the effectiveness of treatment.21–23 Although 90% of the respondents stated that the possibility of genetic testing was available for PAH patients, it is important to recommend the introduction of recent methods of genetic sequencing in daily practice in view of the growing progress in defining the genetic heterogeneity of the disease24 and its role in the stratification of risk.25

In the section on patient care and available resources, it is worth mentioning the availability of most diagnostic techniques in the center itself. However, in the case of genetic testing, ergospirometry and ventilation/perfusion scintigraphy, the availability was limited, although these procedures could be performed by agreement with other hospitals. European Society of Cardiology clinical practice guidelines (2015) recommend ventilation/perfusion scintigraphy due to its high sensitivity. The low implementation of ventilation/perfusion scintigraphy might be potentially compensated with the use of CT pulmonary angiography which is broadly available in most hospitals, and could be a valid alternative.

This aspect highlights the importance of networking and collaboration among different hospitals and referral centers in order to ensure the access of PAH patients to the resources necessary for proper diagnosis and management of their disease.

Regarding pulmonary vascular reactivity test, epoprostenol was the most frequently used vasodilator. Although adenosine and nitric oxide are approved for this purpose, they were only available in the center itself in 30% and 45% of cases, respectively.

A significant percentage of centers use oral or sublingual sildenafil for acute vasodilator testing in PAH, even though this strategy is not contemplated in GPC guidelines, which recommend inhaled nitric oxide, intravenous epoprostenol, and intravenous adenosine.26 In 2015, different publications showed a similar vasoreactivity profile of sildenafil when compared to nitric oxide for acute vasodilator testing in PAH.27 Acute sildenafil administration showed to be safe and simple, with the advantage of no special requirements. Its disadvantage is a slow initial effect (30minutes) and more prolonged effect (hours) that makes it a less-convenient alternative. It is possible that some centers use sildenafil in special situations for logistical reasons.

According to the results, the pharmacological treatments included in the therapeutic algorithm of ESC/ERS guidelines for pulmonary hypertension were available in the hospitals of the participating specialists. However, there was variability in terms of access to certain pharmacological options among the different centers. It should be noted that 75% of the specialists mentioned that the selective prostaglandin IP receptor agonist selexipag10 was not available in their hospital. One potential explanation might be that at the time of the survey, the drug had been recently introduced in the Spanish healthcare system.28 A broader access to other oral drugs, such as ambrisentan, bosentan, and sildenafil was reported. Taking into account the sustainability of the National Healthcare System, the existence of restrictive therapeutic protocols in the hospital was noted, possibly due to budget constraints and promote the introduction of generic drugs with indication for PAH. Patients could be referred to reference hospitals in order to receive pharmacological treatments and mitigate any access problem. Despite the results, in general terms, patients have access to pharmacological treatments. Also, the access situation could be less restrictive than other European countries.

According to the European Union and Ministry of Health guidelines and recommendations in Spain, lung transplantation, pulmonary angioplasty, septostomy, etc. could be performed mainly in specialized HP units. For that reason, the availability in the respondent's centers of surgical options such as atrial septostomy or lung-heart transplantation was limited. As improvement areas, the creation of networks between HP units of different experience and capacity should be promoted in order to share knowledge and practices.

Although there have been important advances in the PAH therapeutic armamentarium, at the time of the survey not all patients respond or maintain a good response to pharmacological treatment. A recent analysis of 1391 patients included in the REHAP registry showed the underuse of lung transplantation for PAH patients.29 The authors pointed out that, as observed in other respiratory diseases, the use of lung or heart-lung transplantation as a treatment for PAH is restricted to highly selected cases, so that half of the patients potentially eligible for transplant do not have access to it. These outcomes could be improved if the referral to hospitals with lung transplantation program was facilitated for patients in the early stages of the disease.29

Access to technical and human resources and to continuing education, the removal of administrative access barriers for drug prescription and the creation of networks between HP units with different experience and capacity, were identified as areas for improvement.

Although the vast majority of the surveyed specialists follow the treatment recommendations of the European Guidelines of PAH, some of them considered that treatment options are conditioned by the existence of restrictive therapeutic protocols in their own hospital.

The analysis of the hospital units dedicated to clinical management of patients with PAH participating in this study, indicates that the majority (90%) are currently implementing ESC/ERS guidelines recommendations for the diagnosis and treatment of pulmonary hypertension. However, more than 60% of respondents mentioned access to technical and human resources, continuing education, and administrative barriers for drug prescription, as areas for improvement.

The AIRE17 Study has been funded by GlaxoSmithKline S.A.

J. Segovia-Cubero and J. de Miguel-Díez received consulting fees from GlaxoSmithKline, S.A. during their participation in the study. M. Cevey and L. Gómez are employees of GlaxoSmithKline, S.A. and have stock options in the company.