Rationale: To date, it remains unclear whether recent changes in the management of patients with systemic sclerosis-associated pulmonary hypertension (SSc-PH) have improved survival. Objectives: To describe a cohort of patients with SSc-PH and compare their characteristics and survival between the last two decades. Methods: Patients with SSc-PH prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Center Registry were grouped into two cohorts based on the date of diagnostic right heart catheterization: cohort A included patients whose disease was diagnosed between 1999 and 2010, and cohort B included those whose disease was diagnosed between 2010 and 2021. Patients' characteristics were compared between the two cohorts. Measurements and Main Results: Of 504 patients with SScPH distributed almost equally between the two cohorts, 308 (61%) had World Symposium on Pulmonary Hypertension group 1, 43 (9%) had group 2, and 151 (30%) had group 3 disease. Patients with group 1 disease in cohort B had significantly better clinical and hemodynamic characteristics at diagnosis, were more likely to receive upfront combination pulmonary arterial hypertension therapy, and had a nearly 4-year increase in median transplant-free survival in univariable analysis than those in cohort A (P, 0.01). Improved transplant-free survival was still observed after adjusting for patients' baseline characteristics. In contrast, for group 2 or 3 patients with SSc-PH, there were no differences in baseline clinical, hemodynamic, or survival characteristics between the two cohorts. Conclusions: This is the largest single-center study that compares clinical characteristics of patients with SSc-PH between the last two decades. Transplant-free survival has improved significantly for those with group 1 disease over the last decade, possibly secondary to earlier detection and better therapeutic management. Conversely, those with group 2 or 3 disease continue to have dismal prognosis.

RATIONALE:Pulmonary hypertension (PH) is associated with significant perioperative morbidity and mortality. We hypothesised that pulmonary arterial hypertension (PAH) composite risk assessment scores could estimate perioperative risk for PH patients when adjusted for inherent procedural risk. METHODS:We identified patients in the Johns Hopkins PH Center Registry that had noncardiac surgery (including endoscopies) between September 2015 and January 2020. We collected information on preoperative patient-level and procedural variables and used logistic regression to evaluate associations with a composite outcome of death within 30 days or serious postoperative complication. We generated composite patient-level risk assessment scores for each subject and used logistic regression to estimate the association with adverse surgical outcomes. We adjusted multivariable models for inherent procedural risk of major cardiovascular events and used these models to generate a numerical PH perioperative risk (PHPR) score. RESULTS:Among 150 subjects, 19 (12.7%) reached the primary outcome, including 7 deaths (4.7%). Individual patient-level and procedural variables were associated with the primary outcome (all p<0.05). A composite patient-level risk assessment score built on three noninvasive parameters was strongly associated with reduced risk for poor outcomes (OR=0.4, p=0.03). This association was strengthened after adjusting the model for procedural risk. A PHPR score derived from the multivariable model stratified patients into low (0%), intermediate (≤10%), or high (>10%) risk of reaching the primary outcome. CONCLUSION:Composite PAH risk assessment scores can predict perioperative risk for PH patients after accounting for inherent procedural risk. Validation of the PHPR score in a multicentre, prospective cohort is warranted.

Children with Down syndrome and pulmonary hypertension (PH) are a unique and challenging group of patients. Down syndrome, or Trisomy 21, affects approximately one in every 600 to 800 live births.1 PH, currently defined as a resting mean pulmonary artery pressure of ≥25 mm Hg, is known to increase morbidity and mortality significantly in this group of patients and has been identified in as many as 28% of all patients with Down syndrome. Furthermore, specific risk factors and comorbidities have been shown to increase the chance of developing PH in this population.2 Careful screening and proper treatment is imperative in children with Down syndrome to prevent the development, recurrence, or progression of PH in this population.Recent findings from Bush et al demonstrate clear clinical characteristics and risk factors for development of PH in children with Down syndrome.2 Prior to this study, data regarding the incidence of PH throughout the Down syndrome lifespan, associations with comorbidities, exacerbating factors, and overall impact of PH in the Down syndrome population were lacking. Most notably, perhaps, was their finding that a vast majority (87%) of patients who suffered from recurrent PH after a previous resolution were classified as World Health Organization (WHO) Group 3 or associated with lung disease. The study also demonstrated that obstructive sleep apnea (OSA), recurrent hypoxia, and aspiration are clear risk factors for development or recurrence of PH. Given these findings, we as providers must take an organized approach in screening for potentially preventable lung insults that contribute to the development and further progression of PH.It is well known that PH in children with Down syndrome is most frequently classified as Group 1 PH (PAH, pulmonary arterial hypertension) associated with congenital heart disease (CHD) or persistent pulmonary hypertension of the newborn (PPHN), and oftentimes a combination of the two.23 For one cohort of children with Down syndrome followed prospectively in the Netherlands, 5.2% had PPHN, which is significantly higher than the reported 0.1% in the general population.3 In the large group of children followed in the Down Syndrome Clinic at Denver Children's Hospital (n=1252), of the 28% identified as having PH, 82% had associated CHD and 45% had PPHN.2 The most common cardiac congenital malformations associated with Down syndrome include atrioventricular canal, patent ductus arteriosus, atrial septal defect, and ventricular septal defect, all of which include cardiac shunts that can lead to PH due pulmonary over circulation.2310 The American Academy of Pediatrics (AAP) recommends an echocardiogram in the first month of life for all babies with Down syndrome; therefore, most are diagnosed and repaired in infancy.5While cardiopulmonary abnormalities including CHD and PPHN are the most common etiology of PH onset in infancy, lung disease is the more common etiology seen after infancy or with recurrent disease. It appears that PH develops more readily from hypoxia in the Down syndrome population, and that children with a prior diagnosis of PH are more likely to develop a recurrence of disease in the context of a respiratory comorbidity such as OSA, intermittent hypoxia, recurrent pneumonia, and chronic aspiration. Given the high rate of respiratory comorbidities in these children, it is not surprising that 87% of children experiencing a second episode of PH after a previous resolution were classified as WHO Group 3.2 For any patient with Down syndrome and PH (or history of PH), a primary pediatric pulmonologist should be identified and follow the patient along with the PH team indefinitely.For those Down syndrome patients who have resolution of their PH, it is imperative they have regular screening for comorbid respiratory conditions despite the presence or absence of symptoms. Given what we know about this population, we are empowered to prevent the recurrence of PH in this high-risk population by continuing to regularly screen for respiratory comorbidities, rather than screening only after echocardiogram evidence of PH becomes apparent.A frequently overlooked cause of PH and other respiratory symptoms in Down syndrome is unrecognized aspiration. Children with Down syndrome are at significant risk for chronic aspiration due to delayed oral development, structural abnormalities, and hypotonia.1 One study of patients with Down syndrome followed in a sleep clinic in the United Kingdom showed 16/17 computerized tomography (CT) scans done on this population revealed findings suggestive of aspiration.4 In the Denver cohort, 35% of all patients with Down syndrome with PH were reported to have chronic aspiration. That number increased to 48% of patients with recurrent PH, highlighting the significant role chronic aspiration can play in children with a history of PH.2 The AAP recommends video fluoroscopic swallow study (VFSS) for any child with Down syndrome with “marked hypotonia, slow feeding, choking with feeds, recurrent persistent respiratory symptoms, or failure to thrive” in the first year of life. They do not provide recommendations for any routine screening.5 We recommend that a VFSS be performed for all children with Down syndrome, despite a presence or absence of aspiration symptoms, as part of the initial comprehensive evaluation for new PH diagnosis, recurrence of previously resolved PH, poorly controlled or worsening PH, and periodically for those with a history of diagnosed aspiration. All patients with presumed or confirmed aspiration should by regularly followed by a feeding therapist as well as a pulmonologist for ongoing assessment and monitoring.There is a significant risk of OSA, found in multiple studies to be present in anywhere from 30% to 79% of all patients with Down syndrome (compared with just 2% of the general pediatric population).12 In the Denver cohort of patients with Down syndrome, 78% of those with PH were also diagnosed with OSA, showing an incredibly high association of the two diseases.2 Because of the known risk factor of OSA in the Down syndrome population, the AAP recommends a sleep study by age 4 years for all children with Down syndrome, and sooner if one exhibits signs or symptoms of sleep-disordered breathing. 5 However, as McDowell explains, relying on parental report is somewhat problematic. Parents of children with Down syndrome consistently underestimate the presence of sleep-disordered breathing. In one study, 69% of parents of children with Down syndrome denied any sleep problems, yet 54% of those same children had abnormal sleep study findings.6 Because of this, we recommend a standardized approach for screening for OSA in patients with history of PH or active disease, instead of determining need based on parental report.For those children with a new diagnosis of PH (or new recurrence), a sleep study should be done as part of initial comprehensive workup, as is recommended with any child with new diagnosis of PH (not just patients with Down syndrome).7 For those with a history of resolved or controlled PH, we feel it is reasonable to be assessed in a sleep clinic annually so that the specialists in that clinic help determine the need for and frequency of sleep studies. And finally, in PH patients with Down syndrome who have lack of improvement or clinical worsening despite optimal PH treatment, sleep studies should be repeated every 1 to 2 years given the high rate of association of OSA and PH. Providers commonly assume that pediatric patients with Down syndrome have low adherence to prescribed respiratory support, and sometimes resist repeating sleep studies if they do not believe their patients will comply with recommendations. However, a recent study showed more than half of children (22/39) had satisfactory and regular usage of prescribed respiratory support, further emphasizing the need for ongoing OSA screening.4 While adenotonsillectomy can improve sleep-disordered breathing in this population, underlying airway structure or dynamics may cause significant residual OSA. Because of this, reassessment after surgery is also imperative.1Children with Down syndrome are known to have an increased incidence of pulmonary abnormalities when compared to the general population. Common airway abnormalities include anomalies such as macroglossia, tonsil and adenoid hypertrophy, laryngomalacia, tracheobronchomalacia, subglottic stenosis, and tracheal stenosis.1 These airway abnormalities predispose patients to intermittent hypoxia, which can lead to the development of PH in this at-risk population. In one review, approximately 50% of patients with upper airway obstruction had PH documented by echocardiogram or cardiac catheterization, with 91% resolution of PH following surgery.8 While we know patients with Down syndrome can also have primary parenchymal lung disease (such as pulmonary hypoplasia, pulmonary lymphangiectasia, lymphoid interstitial pneumonitis, and other interstitial lung disease), they are more likely to have diffuse parenchymal disease from secondary causes such as postinfectious changes, chronic lung disease of prematurity, and chronic aspiration. Interestingly, there are significantly lower rates of asthma in the Down syndrome population, which should prompt the provider to screen for alternative causes of coughing and wheezing.1These well recognized comorbidities highlight the importance of proper screening for pulmonary abnormalities, including advanced imaging with high-resolution chest CT at the time of PH diagnosis or recurrence, and need for good, ongoing pulmonary specialty care. Furthermore, it is has been shown that patients with Down syndrome may not respond to pulmonary vasodilators in the same way as patients without Down syndrome, potentially indicating that ongoing pulmonary (or other) insults have not been properly identified or treated correctly prior to initiation of PH-specific therapy.9 The Pediatric PH Guidelines from the American Heart Association and American Thoracic Society also highlight the importance of identifying and treating primary or secondary respiratory disease prior to the initiation of long-term pulmonary vasodilator therapy.7Given what we currently know about Down syndrome and PH, our PH center at Seattle Children's Hospital has developed guidelines and standards of care for the patient with Down syndrome throughout their lifespan (Table 1). Both inpatient and outpatient PH referrals too often come after months to years of unrecognized pulmonary insults. With proper education and reinforcement of proposed guidelines for screening, our hope is that comorbidities are recognized and treated prior to the development of or worsening of PH, ideally prior to referral to the PH center, but certainly as part of the ongoing, comprehensive care of the child with Down syndrome and PH.

The symptoms of chronic thromboembolic pulmonary hypertension (CTEPH) are nonspecific, and in 25% of patients, a prior episode of pulmonary embolism cannot be identified; therefore, the diagnosis is often delayed (1–4). This delay can impact patient outcomes, given the poor prognosis of untreated CTEPH (5). An incorrect diagnosis is also detrimental, because CTEPH is potentially curable with pulmonary thromboendarterectomy (PTE), whereas other forms of pulmonary hypertension (PH) are not (6, 7). Diagnostic algorithms for the evaluation of PH consistently advocate the use of ventilation–perfusion ( _ V= _ Q) scanning to screen for chronic thromboembolic (CTE) disease (7–9). Despite these recommendations, a significant proportion of patients evaluated for PH do not undergo appropriate testing (10, 11). Given the discrepancy between guidelines and clinical practice, and given the relative paucity of direct comparisons, we sought to assess the diagnostic accuracy of _ V= _ Q scanning compared with computed tomographic pulmonary angiography (CTPA) in patients with proven CTEPH. Furthermore, unlike previous studies comparing these modalities, we performed this study at PH referral centers without PTE programs to increase generalizability. Using the Johns Hopkins Pulmonary Hypertension Program (JHPHP) Registry and the University of Texas Southwestern Medical Center Pulmonary Hypertension Center (UTSWPHC) Registry, a retrospective cohort study was conducted to identify patients with CTEPH who underwent both _ V= _ Q scanning and CTPA and to assess rates of discordance between these imaging modalities. Each center’s registry has been approved by their respective institutional review boards. CTEPH was defined by thromboembolic disease detected by pulmonary angiography and the presence of precapillary PH detected by right heart catheterization (RHC). Data were collected regarding patient demographics, comorbidities, clinical characteristics, and the diagnostic RHC. The diagnostic workup, consisting of _ V= _ Q scanning, CTPA, and pulmonary angiography, was reviewed for each patient. This included studies performed at JHPHP, UTSWPHC, and referral institutions. To preserve the “real-world” applicability of the study, the initial radiology reports were used in lieu of having the scans reinterpreted. Consistent with similar studies, _ V= _ Q scan results were analyzed with one threshold that included highand intermediate-probability _ V= _ Q scans as indicative of CTEPH and with a stricter threshold that included only high-probability scans (12, 13). Two-tailed Student’s t tests were performed to compare continuous variables between cohorts. For categorical variables, Fisher’s exact test was used. Odds ratios (ORs) were used to compare the rates of positive _ V= _ Q scan results and positive CTPA results. P values less than or equal to 0.05 were considered significant. Sixty-five patients from JHPHP and 54 patients from UTSWPHC were identified with a diagnosis of CTEPH confirmed by RHC and pulmonary angiogram. Of these 119 patients, 91 had both _ V= _ Q and CTPA scans. Table 1 shows the baseline characteristics of the combined cohort, stratified by those with and those without discordance between imaging modalities. There were no differences in age, race, functional status, 6-minute walk distance, or pulmonary function test results. Women were more likely to have discordant results than men, and patients with concordant findings had a higher mean pro-brain natriuretic peptide. There were no differences in rates of distal disease or PTE. There was no difference in the comorbidities between groups (data not shown) or in hemodynamic parameters (Table 1). Among the 91 patients who underwent both _ V= _ Q scanning and CTPA, 90 (98.9%) had an intermediateor high-probability _ V= _ Q scan versus 60 (65.9%) with CTE disease detected by CTPA (OR of positive _ V= _ Q vs. positive CTPA, 46.5; 95% confidence interval [CI], 6.1–349.8). Using stricter criteria of considering only high-probability _ V= _ Q scans indicative of CTEPH, 89.0% of the _ V= _ Q scans were positive versus 65.9% of CTPA scans (OR of positive _ V= _ Q vs. positive CTPA, 4.2; 95% CI, 1.9–9.2). Concordant _ V= _ Q scan and CTPA findings were seen in 61 of 91 patients (67.0%), and 30 patients (33.0%) had discordant findings. In all cases of discordance, the _ V= _ Q scan detected thromboembolic disease, whereas the CTPA scan did not (Figure 1). Of the 91 CTPAs, 64 (70.3%) were performed at referring institutions. There was no statistically significant difference in the rate of negative CTPA performed at referral institutions versus at UTSWPHC or JHPHP (P = 0.09). To account for advances in CTPA scanner technology, the rate of discordance was evaluated by era by splitting the time period analyzed into three equally long periods. There was no difference in rates of discordance (P = 0.74) or in CTPA sensitivity (P = 0.81) by era. In our retrospective cohort of patients with CTEPH derived from two large academic medical centers, we demonstrate that in 33% of cases, there was discordance between _ V= _ Q and CTPA imaging. In all cases of discordance, the _ V= _ Q scan was positive and the CTPA was negative for CTE disease, corresponding to a sensitivity of 98.9% for _ V= _ Q scanning compared with 65.9% for CTPA. When _ V= _ Q scanning and CTPA have been compared directly, _ V= _ Q scans have been consistently more sensitive for the detection of CTEPH (12, 13). Although our study confirms prior findings, importantly, it extends the generalizability of these results to academic centers without PTE programs. The “real-world” applicability of our findings is furthered because our study relied on Supported by National Heart, Lung, and Blood Institute grant HL125175 and the Scleroderma Foundation (S.C.M.). K.C. has received research support from with Actelion, Bayer, Geno Pharmaceuticals, the National Institutes of Health (NIH), SoniVie, and United Therapeutics and has received reimbursement for work on advisory boards for Actelion and United Therapeutics. S.C.M. has received research support from the NIH and the Scleroderma Foundation, has received consulting fees from Actelion and United Therapeutics, and serves on the Pulmonary Hypertension Association Scientific Leadership Council and the Patient-Centered Outcomes Research Institute Rare Disease Advisory Panel.

Pulmonary hypertension (PH) complicates common diseases and can lead to worsening symptoms and increased mortality. A specific group of PH, pulmonary arterial hypertension (PAH), World Health Organization Group 1, may present to the emergency department (ED). We review common ED presentations of patients with PAH such as cardiac arrest/sudden death, right ventricular failure, syncope, hypoxemic respiratory failure, arrhythmias, hemoptysis, pulmonary embolism, chest pain/left main compression syndrome, infection, and considerations for PAH medication administration. We include a case study to illustrate a real example with a positive outcome, and an algorithm for evaluating and triaging patients with PAH in the ED. The ability to recognize, triage, and communicate changes in PAH disease status in a multidisciplinary team approach between the patient, family, specialty pharmacy, and specialized health care providers such as the PH team, is essential for ED providers who are evaluating and treating patients with PAH.

Morbidity and mortality risk increase considerably for patients with pulmonary hypertension (PH) undergoing non-cardiac surgery. Unfortunately, there are no comprehensive, evidence-based guidelines for perioperative evaluation and management of these patients. We present a brief review of the literature on perioperative outcomes for patients with PH and describe the implementation of a collaborative perioperative management program for these high-risk patients at a tertiary academic center.

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.

Pulmonary arterial hypertension (PAH) is a rare and often terminal disease. It is often associated with high symptom burden and decreased quality of life, in addition to overall high mortality. Previously, the disease's mortality rate was about 50% over 2.8 years and life expectancy was approximately 4 years from the onset of symptoms.1 Over the last decade there have been major improvements in the medical management of PAH with the introduction of specific treatments for PAH including prostanoids, phosphodiesterase type 5 (PDE-5) inhibitors, and endothelin receptor antagonists. As a result, disease progression is delayed in some cases. However, as advances in medicine have helped to extend life, patients often struggle with not only the physical progression of disease and uncomfortable side effects of these novel drugs, but also with the psychosocial challenges that come with a chronic illness. Anxiety, depression, difficulty maintaining relationships, difficulty with body image, change in lifestyle, and financial struggles are a few examples.1 Furthermore, by the time patients are diagnosed with the disease, most have been seen by multiple providers at multiple institutions, which can be emotionally burdensome.2 Given the complexities of this disease and the fragility of its treatment, a paradigm shift is emerging in the medical management of the disease toward one of holistic patient-centered care, with the hope of improving patient engagement, compliance, and overall outcomes.3Part of providing the best holistic care possible is performing a comprehensive psychosocial assessment at the time of diagnosis. This can help to address fears about the disease and its treatment; examine its impact on work, family life, and finances; and identify patients at a higher risk for anxiety and depression. One international study performed by a committee of PAH specialists revealed that 56% of patients and caregivers felt that PAH resulted in significant impacts on daily life, 85% of patients had concerns about work, and 67% of patients reported an influence on their sex life.4 Patients reported concerns regarding the effects of family planning as pregnancy carries a significant risk to both the mother and the fetus, as well as concerns that the disease interfered with the ability to play with children and grandchildren and travel.4 Performing a thorough psychosocial evaluation up front can help identify some of these issues and concerns so that they can be appropriately addressed and managed. While we understand that these psychosocial considerations are important, there is a lack of information about what to actually include in that psychosocial evaluation and how to appropriately resolve the issues and provide continued services outside what the medical clinic can offer. Below we share a case study, followed by a sample of questions that can be utilized for a psychosocial evaluation, including suggestions on how one may begin to manage psychosocial distress.Ms. O. is a 33-year-old African-American female with no known past medical history. She has been admitted to the hospital 3 times over the last few months for shortness of breath. During that time, she was treated with antibiotics and inhalers. On this most recent hospitalization, she presented to the hospital with shortness of breath, lower extremity swelling, and abdominal distension for 2 weeks. In the emergency room, she was noted to have a cough and had an oxygen saturation of 90% on room air. She was started on broad-spectrum antibiotics for possible pneumonia. An echocardiogram was also obtained, which was notable for estimated systolic pulmonary arterial pressure >90 mm Hg, severe right ventricular failure, and dilation of the superior vena cava. At that time, the advanced heart failure team—who specializes in pulmonary hypertension (PH)—was consulted for assistance. She was diuresed with a Lasix infusion for volume overload, and a workup for PH was initiated. She explained that her oldest brother died in his 40s with some lung issue, but that she wasn't sure of the details because they did not have a close relationship. A few days later, following diuresis, she underwent a right heart catheterization that showed her calculated pulmonary vascular resistance was 7 Wood units and transpulmonary gradient was >15. She was diagnosed with PAH, likely familial versus idiopathic. The remaining workup was otherwise negative. The decision was made to start her on intravenous Remodulin, uptitrate to the highest tolerated dose, and discharge home with services and with an outpatient follow-up appointment in a PH clinic.When the drug was initially started, Ms. O. was in the intensive care unit (ICU) and was undergoing multiple tests and procedures, so she didn't have much time to process her diagnosis. Once she was doing well on the floor and the drug was being slowly uptitrated, she began to express to the nurse her concerns and worries about returning home. The palliative care team was consulted to assist with managing her anxiety and discussing advanced care planning. On initial assessment, the palliative care social worker learns that Ms. O. is very angry at the medical team for not discovering her PAH earlier. She feels that no one is listening to her and that the team is trying to "rush" her out of the hospital. She is worried about going home and worried about her partner and how her illness will affect their relationship. Ms. O. also has financial concerns, as her partner recently lost his job and she is unsure whether she will be able to return to work. Over the course of a few days, the palliative care team works with Ms. O. to help develop a plan to manage her anxiety at home. The social worker uses reflective statements and summarizing and some motivational interviewing techniques (Table 1) to provide Ms. O. the space to process her illness.5 The chaplain works with her on some breathing exercises, and they are able to connect her with a therapist in the community that specializes in chronic illness management. The palliative care team also agrees to follow her in their clinic once a month for advanced care planning.A new diagnosis of PAH can be overwhelming not only physically, but also emotionally and spiritually. It often affects a patient's ability to engage in meaningful activities, leaving them at high risk for psychosocial distress. Validating the multiple losses that come with illness is important to building strong relationships with patients and families.1 How can we best approach patients holistically to ensure we are screening for psychological problems at diagnosis? Some sample questions are provided in Table 2, which could be useful when completing a holistic psychosocial assessment. During the initial screening, one can utilize some of the questions, and then follow up with more in-depth assessment after initial diagnosis, as it can be difficult for patients to process a lot of information after receiving a new diagnosis.4 For Ms. O., it was important for her to express her feelings of frustration with the health care team and have a space to process what was happening to her both physically and emotionally. In listening to her concerns, the social worker and chaplain offered her space to process and assistance in determining a plan to help her better manage her illness.There is little research for PAH and palliative care, but it is important to involve palliative care early to assist with symptom management and evaluate for psychosocial challenges.1 In this case, the palliative care team was consulted early and was able to help create a plan to support the management of all aspects of Ms. O.'s illness. Conversations around care planning can begin when a patient is first diagnosed with PH. The palliative care team was able to implement strategies of motivational interviewing and utilization of reflection statements to help the patient process her feelings therapeutically.As management of PH continues in the years to come, a holistic approach by the health care team will be essential, as it will result in more patient engagement and self-care, which will ultimately lead to improved patient outcomes.3 We provide a sampling of questions that can be utilized for a psychosocial assessment and suggest having experts from palliative care involved early in the disease process.

Medications for pulmonary hypertension (PH) are expensive and often require prior authorization from insurance payers. The task of submitting prior authorization requests and appealing denials can burden PH practices with a heavy workload and delay or interrupt medical treatment. However, it is possible to reduce this burden, improve success rates, and reduce waiting times by implementing a standard office workflow for managing the prior authorization process. Such a system involves several key components: assessment of existing staff and level of expertise; dedicated office staff to oversee the process from start to finish; streamlined gathering, storage, and transmittal of patient documents; direct communication with pharmacies and Risk Evaluation Mitigation Strategy programs; and careful documentation of PH diagnosis and treatment plans for a given patient, aimed at reducing the necessity for appeals. This article reviews prior authorization strategies and systems used at PH clinics, and case studies in other therapeutic areas that demonstrate how such systems can reduce staff time and waiting time for initiation of medications while improving the rate of success. The article also describes the special challenges of requesting prior authorization for PH medications prescribed to pediatric patients.

Managing pulmonary arterial hypertension (PAH) treatment is a complex balance of achieving the desired medication effect versus maintaining safe and tolerable side effects for the patient. The “balancing act” intensifies when PAH patients are faced with multiple disease states that require treatment medication. This article will focus on the drug-drug interactions that must be considered in PAH patients with concomitant human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV) infection.

While I have been a member of PHPN since my career as a pediatric nurse practitioner shifted to pediatric pulmonary hypertension (PH) in 2016, this year was my first experience at the Pulmonary Hypertension Association's (PHA) International Conference and Scientific Sessions. It is powerful to have medical providers, patients, families, and industry members come together in celebration of treatment of a disease that we all fight every day. When put into practice, it generates an energy that is palpable. This year's theme, “PHinding Your Hope,” seemed all too fitting. I recognized hope in the research presented, the strength of the community, and the stories of the patients—showing how far we have advanced in the treatment of pulmonary vascular disease.I arrived at the Renaissance Orlando on Thursday afternoon, ready to present my pediatric case study at the poster session. Even before setting up, I was struck by the closeness of the PH community. I stood at check-in with one of my former patients as she pointed out “PHriends”: other patients she knew from the growing online community, many of whom she had not even met in person. However, they all knew each other's stories. There were immediate hugs and laughter and natural conversation, and it seemed like they had just seen each other last week.The poster session brought together not only PH providers, basic scientists, and industry representatives, but patients and families interested in the newest innovations in pulmonary vascular disease. Many questions on my case study came from adult patients in the form of, “What is it like to treat kids?” or “They use Remodulin on infants too?” In addition to asking questions, these patients also shared personal experiences. There were many tales of survival told. I heard from a woman, now in her 30s, who has PH from Eisenmenger's physiology related to an unrepaired congenital cardiac defect. She stated that she is enjoying her life despite her “continuous medication, oxygen use, and blue lips.” It was my first exposure to the array of patient stories I would hear over the next several days.I spoke with the father of a now adult patient about their family's journey living with a chronic illness. They have relied on this conference as part of their support system through the years. He articulated to me the importance of the lasting friendships they have made. While they only see each other at Conference, they maintain contact via mail, email, and now social media. His daughter has developed from a child seeking connection and normalcy to a young woman who is now leading patient sessions as a role model for the next generation of pediatric patients. We discussed the difficulty of transition and moving from pediatric to adult care. He offered valuable insight about the importance of early discussions about transition. He eloquently emphasized that detachment from the pediatric care team can be just as difficult for mom and dad as for the patient.On Friday morning, the scientific sessions opened with a poignant keynote lecture from Dr Roham Zamanian. He discussed the enormous potential for precision medicine in the future for the treatment of pulmonary vascular disease. The longer I serve as a practitioner in this field, the more I appreciate the heterogeneity of the disease within my own patient population. There isn't a “typical” response to treatment. As we look to more novel therapies, it appears that individually tailored treatment may be the direction our field is headed. As a pediatric provider, I appreciated the well-rounded conference agenda, inclusive of many pediatric-focused topics. Dr Stephanie Handler gave a nice overview of “Congenital Heart Disease and PH: Novel Treatment Approaches,” where she discussed more controversial approaches such as “treat and repair” and prostacyclin therapy for the single ventricle. Dr Uyen Troung's colorful 3-D MRI images highlighted the difference in flow patterns of children with pulmonary vascular disease in her talk, “Imaging the Right Ventricle.”Throughout the weekend, the exhibit hall was filled with people donning purple-dyed hair and zebra-print everything. It was a place of socialization and connection for patients and professionals alike. The VIPHaware pin collection spread among the vendors made visiting the booths seem like a fun scavenger hunt, with the added benefit of obtaining pharmaceutical information with your collectable. If you met the right people on the conference floor, you may have encountered a few special pins, including a tribute to Sean Wyman and a PH Warrior pin designed by PH patient Jenny Janzer. Other activities such as face painting and healthy cooking demonstrations were popular with adults and children alike.There was a constant crowd surrounding the Team PHenomenal Hope booth, where 2 Peloton® stationary bikes were set for a stream of cyclists riding for patients in their “Let Me Be Your Lungs” program. Team PHenomenal Hope is a nonprofit group committed to increasing awareness about PH, raising funds for medical research and patient services, and creating a stronger PH community. Team members are volunteer endurance athletes who generate funds and awareness through races of their own choosing. They are paired with PH patients who do not have the exercise tolerance to complete the race themselves. Patients were present in the booth, cheering on their surrogates as they raised money toward research and Team PHenomenal Hope's new patient fund. The enthusiasm of Dr Patricia George, Team PHenomenal Hope's cofounder, was infectious as she urged participants to go farther than they expected they could go—although it was difficult to keep up with her energy and miles as she topped the leaderboard. I even got to participate in the action, riding for one of my own patients. I hopped on the bike after getting a high five from Carl Hicks, PHA's former executive vice president, who had just finished his own PHenomenal ride.One of the advantages of attending an event like PHA's International Conference and Scientific Sessions as a provider is the opportunity to participate in some of the patient-led sessions. Hearing their perspective on living with PH is something we can't learn from a textbook or a research- based lecture. I listened to my former patient, now a UCLA nursing student, discuss her experiences with “Dating, School, and Work With PH.” She and 2 other young adults presented strategies for work-life balance, conserving energy with a busy schedule, and how to talk to professors/employers/partners about illness. Watching these successful young adults reminded me that we are ushering a new generation of pediatric PH patients toward a future that includes college, careers, and marriage. It wasn't long ago that we didn't have the treatments available to guide pediatric PH patients to adulthood. Now we are working on transition programs to empower adolescents to take ownership of their health as they move in the direction of independence. To see a former patient successfully focusing on new opportunities brings me such pride as well as hope for my other patients as they head into adulthood.There is a unique relationship between pediatric PH patients and their providers. We are with the patient and their family from a life-changing diagnosis through their treatment course until they are old enough to move on. We are with them through ICU stays and well visits. We know their siblings, visit their schools, and know where they go on vacation. We cheer on their successes. We are with them on their journey. As we develop more advanced PH therapies, we are offering them hope. There was no sweeter example of this at the conference than Dr Russel Hirsch and his young patient, Riley, presenting their story at the Journey's Lunch. When it was Riley's turn to speak, she giggled nervously and waited for Dr Hirsch's whispered prompt. “My doctor is the best!” she exclaimed. As Dr Hirsch recounted Riley's PH journey, she tapped him on the arm and whispered in his ear, to which he responded, “My patient is the best!”

Pulmonary hypertension (PH) is a complex, life-threatening disease. Development of pulmonary hypertension centers is recommended by pulmonary hypertension best practice guidelines and patient organizations to successfully care for patients. However, very little is published on the characteristics of these centers or the daily management required to care for this complex patient population.

Background: Supraventricular arrhythmias (SVA) occurrence in pulmonary arterial hypertension (PAH) patients may cause clinical deterioration and affect overall prognosis. Aim: To assess SVA incidence in idiopathic (IPAH) and systemic sclerosis related PAH (SScPAH) and evaluate risk factors, management, and impact on mortality. Methods: We collected baseline demographics, hemodynamics, six minute walking distance, and NTproBNP from consecutive IPAH or SScPAH patients prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Registry from January 2000 to July 2016. During follow-up visits SVA occurrence, therapies and long-term outcome were recorded. Results: Among 317 patients (201 SScPAH, 116 IPAH, mean follow up of 67±51 months), 42 had SVA (34 atrial fibrillation, 18 atrial flutter and 4 atrial ectopic tachycardia). Incidence was slightly higher in SScPAH (13.9 vs 12.1%, p=0.22). In 64.3% of cases at least a second episode occurred. Most SVA were associated with hospitalization (90.5%). Electrical or pharmacological cardioversion was attempted in most cases. Patients with SVA had higher right atrial pressure, pulmonary wedge pressure, NTproBNP (p<0.05) and higher prevalence of thyroid disease (69 vs 42.5%, p=0.001). Higher mortality was observed in patients with SVA (p=0.045). Recurrent SVA had higher mortality compared to single SVA episode (p=0.002). IPAH with SVA and SScPAH without SVA had a similar long term mortality (Log Rank p 0.098). SScPAH with SVA had the worst prognosis. Conclusion: SVA occurrence in PAH is a matter of concern, acutely leading to clinical deterioration and ultimately impacting long-term prognosis. Therapeutic strategies aimed at preventing SVA recurrence may be a relevant goal.

BACKGROUND Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH. METHODS In this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co-primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints. RESULTS At 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6-32.9] vs. 32.5 g [IQR, 23.2-41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0-5.7] vs. 6.9 Wood units [IQR, 4.0-12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8-3.5] vs. 1.4 ml/mm Hg [IQR 8.9-2.4]; P < 0.0001) and mean ( ± SD) tricuspid annular plane systolic excursion (2.2 ± 0.12 cm vs. 1.65 ± 0.11 cm; P < 0.0001), 6-minute walk distance (395 ± 99 m vs. 343 ± 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 ± 1,127 pg/ml vs. 1,578 ± 2,647 pg/ml; P < 0.05). CONCLUSIONS Up-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT01042158).

RATIONALEPulmonary arterial hypertension (PAH) is a medically incurable disease resulting in death from right ventricular (RV) failure. Both pulmonary vascular and RV remodeling are linked to dynamic changes in the microvasculature. Therefore, we hypothesized that circulating angiostatic factors could be linked to outcomes and represent novel biomarkers of disease severity in PAH.OBJECTIVESWe sought to determine the relationship of a potent angiostatic factor, endostatin (ES), with disease severity and mortality in PAH. Furthermore, we assessed genetic predictors of ES expression and/or function and their association with outcomes in PAH.METHODSWe measured levels of serum ES in two independent cohorts of patients with PAH. Contemporaneous clinical data included New York Heart Association functional class, 6-minute-walk distance, invasive hemodynamics, and laboratory chemistries.MEASUREMENTS AND MAIN RESULTSSerum ES correlated with poor functional status, decreased exercise tolerance, and invasive hemodynamics variables. Furthermore, serum ES was a strong predictor of mortality. A loss-of-function, missense variant in the gene encoding ES, Col18a1, was linked to lower circulating protein and was independently associated with reduced mortality.CONCLUSIONSOur data link increased expression of ES to disease severity in PAH and demonstrate a significant relationship with adverse outcomes. Circulating ES levels can be genetically influenced, implicating ES as a genetically determined modifier of disease severity impacting on survival. These observations support serum ES as a potential biomarker in PAH with the capacity to predict poor outcomes. More importantly, this study implicates Col18a1/ES as a potential new therapeutic target in PAH.

Treatment of pulmonary arterial hypertension (PAH), a disease of the pulmonary vessels causing right ventricular (RV) failure and death, has evolved. No validated methods for assessing response to PAH therapies beyond impact on survival exist; thus there is a need to identify surrogate endpoints for PAH. Studies have shown tricuspid annular plane of systolic excursion (TAPSE) as a marker of RV function correlating with survival. Clinically-relevant changes in TAPSE in response to PAH therapy have yet to be described. Consecutive treatment naive patients with PAH diagnosed by right heart catheterization were included. For each patient, a transthoracic echocardiogram (TTE), six-minute walk test (6MWT), N-terminal pro-BNP, and Medical Outcomes Short Form-36 survey (SF-36) was obtained at baseline and 3 months. Several estimates of the minimal important difference (MID) of TAPSE will be made by both distribution- and anchor-based methods regressing change in TAPSE with treatment against change in 6MWT and SF-36. A consensus estimate will be defined using triangulation methodology. 25 subjects were enrolled; 11 have completed at least 3 months of PAH therapy. Mean TAPSE improved by 0.2 cm (SD 0.4 cm). Additionally, the 6MWT improved by a mean of 81.9 m (SD 87.4 m). The MID will be determined when all subjects have completed study protocol. These preliminary data indicate TAPSE may be responsive to PAH-specific therapy in patients with PAH. With completion of the study protocol, the MID for TAPSE will be determined using multiple methods. Defining the MID for TAPSE will offer a clinically relevant, widely available metric to assess response to therapy in PAH.