Pulmonary Hypertension Care Center Research Articles

Pulmonary Hypertension in Women.

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by elevated pulmonary artery pressure and increased pulmonary vascular resistance. Females have a higher incidence of PAH, which is reflected globally across registries in the United States, Europe, and Asia. However, despite female predominance, women had better outcomes compared with male patients, a finding that has been labeled the "estrogen paradox." Special considerations should be given to women with PAH regarding sexual health, contraception, family planning, and treatment before, during, and after pregnancy. Pregnant women with PAH should be referred to a pulmonary hypertension care center; a multidisciplinary team approach is recommended, and Cesarean section is the preferred mode of delivery. While pregnancy outcomes have improved over the years with PAH-specific therapy, pregnancy portends a high-risk for those with PAH. Continued research is needed to tailor PAH treatment for women.

Anticoagulation in pulmonary arterial hypertension - association with mortality, healthcare utilization, and quality of life: The Pulmonary Hypertension Association Registry (PHAR).

Routine long-term anticoagulation in pulmonary arterial hypertension (PAH) is controversial. To date, anticoagulation has been found to be beneficial or neutral in idiopathic disease (IPAH) and neutral-to-harmful in connective tissue disease (CTD-PAH). We sought to examine the association between anticoagulation and mortality, healthcare utilization, and quality of life (QoL) in PAH. The PHAR is a prospective registry of PAH patients referred to 58 pulmonary hypertension care centers in the United States. We compared patients who received anticoagulation during enrollment (questionnaire documented) to those who did not. Cox proportional hazard models were used for mortality, Poisson multivariate regression models for healthcare utilization, and generalized estimating equations for QOL RESULTS: Of 1175 patients included, 316 patients were treated with anticoagulation. IPAH/hereditary PAH (HPAH) comprised 46% of the cohort and CTD-PAH comprised 33%. After adjustment for demographics, clinical characteristics, site and disease severity, anticoagulation was not associated with mortality in the overall population (HR, 1.00; 95% CI, 0.72-1.36), IPAH/HPAH (HR, 1.19; 95% CI, 0.74-1.94), or CTD-PAH (HR 0.87; 95% CI, 0.53-1.42). Anticoagulation was associated with an increased rate of emergency department visits (IRR: 1.41), hospitalizations (IRR: 1.30), and hospital days (IRR 1.33). QOL measured by emPHasis-10 score was worse in patients receiving anticoagulation (mean difference 1.74; 95% CI 0.40-3.09). Anticoagulation is not associated with higher mortality, but is associated with increased healthcare utilization in the PHAR. PAH-specific QoL may be worse in patients receiving anticoagulation. The risks and benefits surrounding routine prescription of anticoagulation for PAH should be carefully considered.

Hispanic Ethnicity and Social Determinants of Health in Pulmonary Arterial Hypertension: The Pulmonary Hypertension Association Registry.

Rationale: There is a noticeable underrepresentation of minorities in clinical trials and registries in pulmonary arterial hypertension (PAH). Prior studies evaluating the association between Hispanic ethnicity and clinical outcomes in patients with PAH have not assessed the socioeconomic profile of Hispanic individuals or the significance of social determinants of health in clinical outcomes. Objectives: To determine the association between Hispanic ethnicity, social determinants of health, and clinical outcomes in PAH. Methods: This was a prospective cohort study of adult participants with PAH enrolled in the Pulmonary Hypertension Association Registry, a multicenter U.S.-based registry of patients treated at pulmonary hypertension care centers. Participants were classified as Hispanics and non-Hispanic White individuals, based on self-reported ethnicity. A comparison of baseline clinical and sociodemographic characteristics between groups was performed as well using absolute standardized differences (ASD). The primary outcome of the study was to assess transplant-free survival between Hispanics and non-Hispanic White individuals. A Cox proportional hazards model was used for the multivariable analysis after adjusting for age, sex, PAH etiology, annual income, education level, and health insurance. Results: A total of 683 individuals were included, 98 (14.3%) of Hispanic ethnicity. Hispanic patients had impaired access to health care (31.6% vs. 12.9% Medicaid/uninsured; ASD, 0.35), lower education level (72.6% vs. 94.0% high school graduates or higher; ASD, 0.60), and lower annual income (32.0% vs. 17.4% with income <20,000 U.S. dollars; ASD, 0.47), compared with non-Hispanic White individuals. Hispanic patients had a higher frequency of emergency room visits and a higher number of hospitalizations, despite having similar disease severity (incidence rate ratio, 1.452; 95% confidence interval [CI], 1.326-1.590; and 1.428; 95% CI, 1.292-1.577, respectively). Although the unadjusted analysis showed a lower transplant/death hazard ratio for Hispanics (hazard ratio, 0.47; 95% CI, 0.24-0.94; P = 0.032), there was no association between Hispanic ethnicity and outcome in the multivariable model after adjusting for social determinants of health and other covariates (HR, 0.76; 95% CI, 0.35-1.62; P = 0.474). Conclusions: Hispanic ethnicity was not associated with differences in survival after adjusting for social determinants of health and other factors. Social determinants of health are important to consider when assessing the association between ethnicity and outcomes in PAH.

Perspectives on Mental Health Evaluation in Pediatric Pulmonary Hypertension: A Call to Action

Background The already high rates of anxiety and depression among healthy children have increased further since the COVID-19 pandemic began in early 2020. Prepandemic data suggest children with chronic disease were already experiencing increased rates of anxiety and depression as compared to their healthy peers. There is currently a paucity of literature on the prevalence of anxiety and depression in patients with pediatric pulmonary hypertension. In addition, there are no practice recommendations regarding mental health screening in this population. Implications for Providers We evaluated provider perception of mental health screening at 14 pediatric pulmonary hypertension care centers across the United States and Canada using a cross-sectional survey. Thirty-seven providers from 14 pediatric pulmonary hypertension centers in North America completed the survey. Conclusion Health care providers caring for pediatric pulmonary hypertension patients perceive their patient cohort to frequently experience anxiety and depression. In addition, these providers believe that their patients would benefit from formalized, and routine, assessment of anxiety and depression with referral to mental health services as appropriate. This highlights the need to better understand the prevalence of anxiety and depression in pediatric pulmonary hypertension patients and to establish formal mental health screening practices within pediatric pulmonary hypertension care centers.

Health-related quality of life and hospitalizations in chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension: an analysis from the Pulmonary Hypertension Association Registry (PHAR).

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, morbid, potentially curable subtype of pulmonary hypertension that negatively impacts health-related quality of life (HRQoL). Little is known about differences in HRQoL and hospitalization between CTEPH patients and idiopathic pulmonary arterial hypertension (IPAH) patients. Using multivariable linear regression and mixed effects models, we examined differences in HRQoL assessed by emPHasis-10 (E10) and SF-12 between CTEPH and IPAH patients in the Pulmonary Hypertension Association Registry, a prospective multicenter cohort of patients newly evaluated at a Pulmonary Hypertension Care Center. Multivariable negative binomial regression models were used to estimate incidence rate ratios (IRR) for hospitalization amongst the two groups. We included 461 IPAH patients and 169 CTEPH patients. Twenty-one percent of CTEPH patients underwent pulmonary thromboendarterectomy (PTE) before the end of follow-up. At baseline, patients with CTEPH had significantly worse HRQoL (higher E10 scores) (ß 2.83, SE 1.11, p = 0.01); however, differences did not persist over time. CTEPH patients had higher rates of hospitalization (excluding the hospitalization for PTE) compared to IPAH patients after adjusting for age, sex, body mass index, WHO functional class and six-minute walk distance (IRR 1.66, 95%CI 1.04–2.65, p = 0.03). CTEPH patients who underwent PTE had improved HRQoL as compared to those who were medically managed, but patients who underwent PTE were younger, had higher cardiac outputs and greater six-minute walk distances. In this large, prospective, multicenter cohort, CTEPH patients had significantly worse baseline HRQoL and higher rates of hospitalizations than those with IPAH. CTEPH patients who underwent PTE had significant improvements in HRQoL.

The Relationship between Anticoagulation and Mortality in Pulmonary Arterial Hypertension: The Pulmonary Hypertension Association Registry (PHAR)

PurposeLong-term anticoagulation (AC) in pulmonary arterial hypertension (PAH) remains controversial, with prior cohorts reporting 28-66% of participants using AC. In idiopathic PAH (IPAH), AC is associated with improved survival or neutral effect, but may be detrimental in those with PAH from connective tissue disease (CTD-PAH). We sought to evaluate the relationship between AC use and mortality in PHAR, a multi-center prospective registry which enrolled patients referred to pulmonary hypertension care centers between 2015-2020.MethodsForty-seven centers collected clinical characteristics, including PAH-specific therapy and survival, at roughly 6month intervals. We compared participants who received AC at baseline to those who did not. We excluded participants <18 years old and with PAH from congenital heart disease. Mortality was assessed using Kaplan-Meier plots and cox regression analysis adjusted for age, sex, body mass index, race, center, mean pulmonary artery pressure, functional class, and use of PAH specific therapy.ResultsThere were 817 participants who met inclusion criteria. The cohort had a mean age of 56 years, 76% were female, 41% had a diagnosis of IPAH, and 34% had a diagnosis of CTD-PAH. Most participants, 85%, had WHO functional class II-III disease. Overall, 21% of participants were on AC at enrollment; 26% of those with IPAH and 17% of those with CTD-PAH. AC use decreased between 2015 to 2019, from 29% to 19%. Median AC duration was 31 months. AC was not associated with mortality in IPAH (adjusted HR 0.9; CI 0.4-1.9) or CTD-PAH (adjusted HR 1.0; CI 0.4 - 2.5) (Figure).ConclusionAC use in PAH has decreased over time, and is lower than prior registries. AC use is not associated with increased mortality in this analysis of the contemporary PHAR cohort. Analyses examining the relationship between AC use and health care utilization and quality of life are forthcoming. Long-term anticoagulation (AC) in pulmonary arterial hypertension (PAH) remains controversial, with prior cohorts reporting 28-66% of participants using AC. In idiopathic PAH (IPAH), AC is associated with improved survival or neutral effect, but may be detrimental in those with PAH from connective tissue disease (CTD-PAH). We sought to evaluate the relationship between AC use and mortality in PHAR, a multi-center prospective registry which enrolled patients referred to pulmonary hypertension care centers between 2015-2020. Forty-seven centers collected clinical characteristics, including PAH-specific therapy and survival, at roughly 6month intervals. We compared participants who received AC at baseline to those who did not. We excluded participants <18 years old and with PAH from congenital heart disease. Mortality was assessed using Kaplan-Meier plots and cox regression analysis adjusted for age, sex, body mass index, race, center, mean pulmonary artery pressure, functional class, and use of PAH specific therapy. There were 817 participants who met inclusion criteria. The cohort had a mean age of 56 years, 76% were female, 41% had a diagnosis of IPAH, and 34% had a diagnosis of CTD-PAH. Most participants, 85%, had WHO functional class II-III disease. Overall, 21% of participants were on AC at enrollment; 26% of those with IPAH and 17% of those with CTD-PAH. AC use decreased between 2015 to 2019, from 29% to 19%. Median AC duration was 31 months. AC was not associated with mortality in IPAH (adjusted HR 0.9; CI 0.4-1.9) or CTD-PAH (adjusted HR 1.0; CI 0.4 - 2.5) (Figure). AC use in PAH has decreased over time, and is lower than prior registries. AC use is not associated with increased mortality in this analysis of the contemporary PHAR cohort. Analyses examining the relationship between AC use and health care utilization and quality of life are forthcoming.

Clinical Differences and Outcomes between Methamphetamine-associated and Idiopathic Pulmonary Arterial Hypertension in the Pulmonary Hypertension Association Registry.

Rationale: Single-center studies demonstrated that methamphetamine use is associated with pulmonary arterial hypertension (Meth-APAH). We used the Pulmonary Hypertension Association Registry to evaluate the national distribution of Meth-APAH and to compare its impact on patient-reported and clinical outcomes relative to idiopathic PAH.Objectives: To determine if patients with Meth-APAH differ from those with idiopathic PAH in demographics, regional distribution in the United States, hemodynamics, health-related quality of life, PAH-specific treatment, and health care use.Methods: The Pulmonary Hypertension Association Registry is a U.S.-based prospective cohort of patients new to care at a Pulmonary Hypertension Care Center. The registry collects baseline demographics, clinical parameters, and repeated measures of health-related quality of life, World Health Organization functional class, 6-minute walk distance, therapy, and health care use. Repeated measures of functional class, health-related quality of life, type of therapy, emergency department visits, and hospitalizations were compared using generalized estimating equations.Results: Of 541 participants included, 118 had Meth-APAH; 83% of Meth-APAH arose in the western United States. The Meth-APAH group was younger and had a poorer socioeconomic status and lower cardiac index than the idiopathic PAH group, despite no difference in mean pulmonary artery pressure or pulmonary vascular resistance. The Meth-APAH group had a more advanced functional class in longitudinal models (0.22 points greater; 95% confidence interval [CI], 0.07 to 0.37) and worse PAH-specific (emPHasis-10) health-related quality of life (-5.4; 95% CI, -8.1 to -2.8). There was no difference in dual combination therapy; however, participants with Meth-APAH were less likely to be initiated on triple therapy (odds ratio [OR], 0.43; 95% CI, 0.24 to 0.77) or parenteral therapy (OR, 0.10; 95% CI, 0.04 to 0.24). Participants with Meth-APAH were more likely to seek care in the emergency department (incidence rate ratio, 2.30; 95% CI, 1.71 to 3.11) and more likely to be hospitalized (incidence rate ratio, 1.42; 95% CI, 1.10 to 1.83).Conclusions: Meth-APAH represents a unique clinical phenotype of PAH, most common in the western United States. It accounts for a notable proportion of PAH in expert centers. Assessment for methamphetamine use is necessary in patients with PAH.

Demographic, Hemodynamic, and HRQL Differences between Methamphetamine-Associated and Idiopathic PAH: The Pulmonary Hypertension Association Registry

Purpose Single-center studies previously demonstrated that methamphetamine use is associated with pulmonary arterial hypertension (Meth-APAH). We sought to use the Pulmonary Hypertension Association Registry (PHAR) to compare methamphetamine-associated (Meth-APAH) to Idiopathic Pulmonary Arterial Hypertension (IPAH) in the United States. Methods PHAR is a 32-center US-based registry of 478 PAH patients new to care at a Pulmonary Hypertension Care Center. In addition to demographics and clinical parameters, baseline health-related quality of life (HRQL) is quantified by the Medical Outcomes Study Short Form-12 (SF12-PCS - generic-physical & SF12-MCS - generic-mental; higher scores denote better HRQL) and emPHasis-10 (PAH-specific; higher scores denote worse HRQL). We included adults diagnosed with Meth-APAH and, as a control group, IPAH. Differences in demographics and clinical parameters were compared by t-tests and chi-squared tests as appropriate. We tested the association of Meth-APAH and HRQL using multivariate linear regression, adjusting for age, sex, race, and education. Results Of 278 subjects included, 58 had Meth-APAH. Subjects with Meth-APAH were younger, less likely to be insured, college graduates, or married. 83% of subjects with Meth-APAH lived in the Western US. The Meth-APAH group tended to have lower cardiac index, stroke volume index, and higher right atrial pressures. The Meth-APAH group had significantly worse SF12-MCS (-3.85, 95%CI -6.48 to -1.23) and emPHasis-10 (5.79, 95%CI 1.85 to 9.74) scores compared to the IPAH group. The groups had similar SF12-PCS scores (0.79, 95%CI -1.38 to 2.96). Results were similar in incident cases (n=132, data not shown). Conclusion Meth-APAH is an aggressive phenotype most common in the Western US. It accounts for a notable proportion of PAH in PHAR centers. Routine screening for Meth-APAH is necessary, and providers should include drug rehabilitation in their therapy plan.

Editorial introductions

Editorial introductions

PH Professional Network: Roadmap to Accreditation: Practical Aspects

The Pulmonary Hypertension Care Center (PHCC) initiative began accrediting Centers of Comprehensive Care (CCC) in 2014, and Regional Clinical Programs (RCP) as part of a pilot program in 2017, in an effort to improve access to quality pulmonary hypertension (PH) care for patients throughout the United States. The purpose of this column is to present a roadmap to accreditation for PH coordinators and their PH teams. We will highlight the essential role that PH coordinators play in navigating all phases of the accreditation process. Figure 1 represents a recommended approach to the PHCC accreditation process.Figure 1:Organizing the PHCC accreditation process.Figure 1:. Organizing the PHCC accreditation process.

The Pulmonary Hypertension Association Registry: Rationale, Design, and Role in Quality Improvement

The Pulmonary Hypertension Association (PHA) Scientific Leadership Council (SLC) prioritized the development of the PH Care Centers (PHCC) initiative in part to identify centers that adhere to expert consensus diagnostic and treatment guidelines in both community and academic practice settings, decreasing the chances of misdiagnosis and inappropriate medical management. The overall goal of the PHCC is to improve outcomes of patients with pulmonary hypertension (PH). It is generally accepted that measurement of processes and outcomes are required in order to improve quality of care: the degree to which health services increase the likelihood of desired health outcomes and are consistent with current professional knowledge. The PHA Registry (PHAR) was developed to collect data regarding key measures to facilitate the achievement of these goals of the PHCC.

Update on the PHA Pulmonary Hypertension Care Center Network: Early Experience With the National Accreditation Program

World Health Organization (WHO) Group 1 pulmonary hypertension (PH) (PAH, pulmonary arterial hypertension) and WHO Group 4 PH (CTEPH, chronic thromboembolic pulmonary hypertension) are rare diseases of the pulmonary vascular system characterized by elevated pulmonary artery pressure and pulmonary vascular resistance in the absence of elevated left ventricular filling pressures, which may progress to right heart failure and death.1 Left untreated, the median survival for idiopathic (IPAH) and heritable (HPAH) disease is about 2.8 years from diagnosis.2 Adherence to expert consensus guidelines on PH diagnosis and management is of critical importance to correctly target therapy and improve patient outcomes.

PH Roundtable: Center-based Care

As guest editor of this issue, Dr Chakinala organized a group of individuals who each had different perspectives and relationships to Pulmonary Hypertension Care Centers. In conversation among the physicians, nurse, social worker, and patient, they touch on the evolution of care of pulmonary hypertension patients over the past 20 years and the complexity of care that new medications and their side effects create. They discuss the advantages that centers of care can bring to the patients and to the field as a whole from access to experts to multidisciplinary care and clinical research during their lively conversation.

Editorial introductions

Editorial introductions

Pulmonary Hypertension Care Center Network: Improving Care and Outcomes in Pulmonary Hypertension

Pulmonary hypertension (PH) is a chronic, progressive, life-threatening disease that requires expert multidisciplinary care. To facilitate this level of care, the Pulmonary Hypertension Association established across the United States a network of pulmonary hypertension care centers (PHCCs) with special expertise in PH, particularly pulmonary arterial hypertension, to raise the overall quality of care and outcomes for patients with this life-threatening disease. Since the inception of PHCCs in September 2014, to date 35 centers have been accredited in the United States. This model of care brings together physicians and specialists from other disciplines to provide care, facilitate basic and clinical research, and educate the next generation of providers. PHCCs also offer additional opportunities for improvements in PH care. The patient registry offered through the PHCCs is an organized system by which data are collected to evaluate the outcomes of patients with PH. This registry helps in detecting variations in outcomes across centers, thus identifying opportunities for improvement. Multiple tactics were undertaken to implement the strategic plan, training, and tools throughout the PHCC network. In addition, strategies to foster collaboration between care center staff and individuals with PH and their families are the cornerstone of the PHCCs. The Pulmonary Vascular Network of the American College of Chest Physicians believes this to be a positive step that will improve the quality of care delivered in the United States to patients with PH.

Pulmonary Hypertension Care Centers: Hope for the Future From a Patient's and Caregiver's Perspectives

In 1987, after three years of being treated aggressively for asthma and then a prolapsed mitral valve, I was finally diagnosed with primary pulmonary hypertension (PPH). I was told I would be lucky if I lived 2 years without having a heart/double lung transplant and that I didn't have much time to get my affairs in order. There were fewer than 200 patients in the United States at the time. There were no treatment centers, support groups, or even an advocacy group like the Pulmonary Hypertension Association (PHA). I struggled with the loneliness of this diagnosis and the lack of information available.

Pulmonary Hypertension Care Centers: Role of the Review Committee

The Pulmonary Hypertension Care Center (PHCC) program launch is well underway! A key component to the success of this program is the ability to provide a comprehensive review of the site applications, and to include in-depth interviews of program staff and administrators on site visits. The applications and site visits will be handled by members of the PHCC Review Committee, which comprises 23 members in addition to my position as Review Committee Chair, including 12 physicians and 11 allied health care professionals (Table 1). This summer, we completed the PHCC Review Committee training program; committee members underwent comprehensive training on accreditation policy (Figure 1) and application review procedures. There were a total of 6 pilot site applications and site visits, which are now complete. More than half of the committee members had the opportunity to participate in at least one of the pilot site visits as part of their training. These visits also provided important feedback for the PHCC program and specified any needed adjustments to the Center criteria and the application process before the official PHCC program launch. The review committee also held the first voting meetings for the pilot site accreditations to ensure the process was smooth and followed the highest standards toward fulfilling the goals of the PHCC initiative.With the recent advances in the treatment of pulmonary arterial hypertension (PAH), it has become even more important that Centers meet the needs of patients with respect to expertise, access to the most advanced targeted agents, and quality of care. As chair of the PHCC Review Committee, I have been tasked with ensuring that the committee provides a standardized approach to evaluating applications upon receipt, and adheres to the process for conducting site visits and voting provided by the PHCC Oversight Committee and the PHCC Implementation Task Force. I am extremely proud of the team that has been assembled and the intense level of behind-the-scenes work already completed. The PHCC Review Committee is well prepared and eager for the official launch of the PHCC program.

Implementation of the PHA Pulmonary Hypertension Care Center Accreditation Program

In the previous issue of Advances in Pulmonary Hypertension, Dr Studer discussed the emerging evidence suggesting that patients with pulmonary hypertension (PH) managed by specialized centers have improved outcomes compared with those without access to comprehensive PH care. He also summarized some of the anticipated benefits of referral to and collaboration with specialized treatment centers for PH.1 In 2011, the Pulmonary Hypertension Association (PHA) Pulmonary Hypertension Care Center (PHCC) Committee began to explore a process for formal accreditation of PH programs in the United States.