Effects of COVID-19 pandemic on the management of pulmonary hypertension.

The coronavirus of 2019 (COVID-19) disrupted delivery of healthcare. Patients with pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), require significant resources for both diagnosis and management and are at high risk for decompensation due to disruption in their care. A survey consisting of 47 questions related to the care of patients with PH was designed by the American College of Chest Physicians 2020-2021 Pulmonary Vascular Disease (PVD) NetWork Steering Committee and sent to all members of the PVD NetWork, as well as the multiple other professional networks for PH. Participation was voluntary and anonymous. Responses were collected from November 2020 through February 2021. Ninety-five providers responded to this survey. The majority (93%) believe that care of PH patients has been affected by the pandemic. Sixty-seven percent observed decreased referrals for PH evaluation. Prior to the pandemic, only 15% used telemedicine for management of PH patients compared to 84% during the pandemic. Telemedicine was used most for follow up of selected low-risk patients (49%). While 22% respondents were completely willing to prescribe new PAH therapy via telemedicine, 11% respondents were completely unwilling. Comfort levels differed based on type of medication being prescribed. Over 90% of providers experienced disruptions in obtaining testing and 31% experienced disruptions in renewal or approval of medications. Overall, providers perceived that the COVID-19 pandemic caused significant disruption of care for PH patients. Telemedicine utilization increased but was used mostly in low-risk patients. Some providers had a decreased level of comfort prescribing PAH therapy via telemedicine encounters.

Erratum: Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: An analysis of the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211020913.].

Considerations When Selecting Patient-Reported Outcome Measures for Assessment of Health-Related Quality of Life in Patients With Pulmonary Hypertension: A Narrative Review.

It is well established that pulmonary hypertension (PH) places a substantial burden on patients' health-related quality of life (HRQoL). As more effective treatments have been developed for this condition, evaluating treatment benefit based on experiences reported by patients regarding their well-being and physical, social, and emotional functioning has increased. A review of the published literature and clinical trials in PH was conducted to identify and evaluate patient-reported outcome measures (PROMs) that assess PH-specific HRQoL for use in clinical studies. The Cambridge Pulmonary Hypertension Outcome Review, emPHasis-10, Living with Pulmonary Hypertension Questionnaire, and Pulmonary Arterial Hypertension-Symptoms and Impact were selected for in-depth evaluation with respect to their content validity, psychometric properties, interpretation guidelines, conceptual coverage, and administrative feasibility. Recommendations for clinical study end point strategies are provided. The review identified many strengths for each of the PROMs. Content development for all PROMs followed best practices, and any weaknesses in assessment of measurement properties were from a scarcity of available data. Although conceptual coverage and patient burden varied greatly across the PROMs, each provided a unique strength relative to the others, and no one PROM was recommended as most appropriate across all contexts of use. Optimal end point selection for assessing PH-specific HRQoL thus requires consideration of the purpose and situation in which the assessment will be conducted. These recommendations should be considered as a snapshot of a quickly evolving landscape that should be updated as new information emerges.

Utilization of risk assessment tools in management of PAH: A PAH provider survey.

Pulmonary arterial hypertension (PAH) is a chronically progressive fatal disease. A goal-oriented approach to achieve low risk status has been associated with improved survival. A variety of risk stratification tools are available, but use is low. We conducted a survey to assess potential reasons for under-utilization. We conducted a survey-based study of global PAH disease specialists with a goal of assessing risk assessment utilization and identifying modifiable barriers to use. The survey was designed by the American College of Chest Physicians' Pulmonary Vascular Diseases (PVD) NetWork. Respondents were global members of the PVD NetWork and Pulmonary Hypertension Association. Survey invitations were sent electronically to all members. Participation was anonymous and no provider or patient level data was collected. Participants from four countries responded with the majority (84%) being from the United States. Our survey found suboptimal use of any risk stratification tool with 71/112 (63%) reporting use. A total of 85% of the respondents had more than 5 years of experience in managing PAH. REVEAL 2.0 and European Society of Cardiology/European Respiratory Society risk tools were the most commonly used. A total of 44 (65%) surveyed felt that use of risk tools led to change in PAH therapies. Only 6 (9%) felt they prompted additional testing or changed the frequency of follow-up. A total of 5 (7%) reported they prompted goals of care/palliative care discussions and 2 (3%) that they triggered lung transplant referral. The vast majority indicated that incorporation of risk tools into electronic medical records (EMR) would improve utilization. PAH risk assessment tools remain under-utilized. Most respondents were experienced PAH clinicians. More than one-third were not routinely using risk tools. Most felt that risk tools led to PAH therapy changes but few reported impacts on other aspects of care. The most commonly identified barriers to use were time constraints and lack of integration with EMR.

A novel approach to perioperative risk assessment for patients with pulmonary hypertension.

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.

Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: an analysis of the Pulmonary Hypertension Association Registry.

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status and/or POPH diagnosis were associated with treatment and health-care utilization. We performed a cross-sectional study of adults enrolled in the Pulmonary Hypertension Association Registry. Patients with IPAH (n = 344) and POPH (n = 57) were compared. Compared with IPAH, patients with POPH were less likely to be college graduates (19.6% vs. 34.9%, p = 0.02) and more likely to be unemployed (54.7% vs. 30.5%, p < 0.001) and have an annual household income below poverty level (45.7% vs. 19.0%, p < 0.001). Patients with POPH had similar functional class, quality of life, 6-min walk distance, and mean pulmonary arterial pressure with a higher cardiac index. Compared with IPAH, patients with POPH were less likely to receive combination therapy (46.4% vs. 62.2%, p = 0.03) and endothelin receptor antagonists (28.6% vs. 55.1%, p < 0.001) at enrollment with similar treatment at follow-up. Patients with POPH had more emergency department visits (1.7 ± 2.1 vs. 0.9 ± 1.2, p = 0.009) and hospitalizations in the six months preceding enrollment (1.5 ± 2.1 vs. 0.8 ± 1.1, p = 0.02). Both POPH diagnosis and lower education level were independently associated with a higher number of emergency department visits. Compared to IPAH, patients with POPH have lower socioeconomic status, are less likely to receive initial combination therapy and endothelin receptor antagonists but have similar treatment at follow-up, and have increased health-care utilization.

Assessment of right ventricular reserve utilizing exercise provocation in systemic sclerosis.

Right ventricular (RV) capacity to adapt to increased afterload is the main determinant of outcome in pulmonary hypertension, a common morbidity seen in systemic sclerosis (SSc). We hypothesized that supine bicycle echocardiography (SBE), coupled with RV longitudinal systolic strain (RVLSS), improves detection of limitations in RV reserve in SSc. 56 SSc patients were prospectively studied during SBE with RV functional parameters compared at rest and peak stress. We further dichotomized patients based on resting RV systolic pressure (RVSP) to determine the effects of load on contractile response. Our pooled cohort analysis revealed reduced global RVLSS at rest (-16.2 ± 3.9%) with normal basal contractility (-25.6 ± 7.7%) and relative hypokinesis of the midventricular (-14.1 ± 6.0%) and apical (-8.9 ± 5.1%) segments. With exercise, global RVLSS increased significantly (p = 0.0005), however despite normal basal contractility at rest, there was no further augmentation with exercise. Mid and apical RVLSS increased with exercise suggestive of RV contractile reserve. In patients with resting RVSP < 35 mmHg, global and segmental RVLSS increased with exercise. In patients with resting RVSP ≥ 35 mmHg, global and segmental RVLSS did not increase with exercise and there was evidence of exertional RV dilation. Exercise provocation in conjunction with RVLSS identified differential regional contractile response to exercise in SSc patients. We further demonstrate the effect of increased loading conditions on RV contractile response exercise. These findings suggest subclinical impairments in RV reserve in SSc that may be missed by resting noninvasive 2DE-based assessments alone.

Identifying Patients with Pulmonary Arterial Hypertension Using Administrative Claims Algorithms.

Retrospective administrative claims database studies provide real-world evidence about treatment patterns, healthcare resource use, and costs for patients and are increasingly used to inform policy-making, drug formulary, and regulatory decisions. However, there is no standard methodology to identify patients with pulmonary arterial hypertension (PAH) from administrative claims data. Given the number of approved drugs now available for patients with PAH, the cost of PAH treatments, and the significant healthcare resource use associated with the care of patients with PAH, there is a considerable need to develop an evidence-based and systematic approach to accurately identify these patients in claims databases. A panel of pulmonary hypertension clinical experts and researchers experienced in retrospective claims database studies convened to review relevant literature and recommend best practices for developing algorithms to identify patients with PAH in administrative claims databases specific to a particular research hypothesis.

Clinical trial design and new therapies for pulmonary arterial hypertension.

Until 20 years ago the treatment of pulmonary arterial hypertension (PAH) was based on case reports and small series, and was largely ineffectual. As a deeper understanding of the pathogenesis and pathophysiology of PAH evolved over the subsequent two decades, coupled with epidemiological studies defining the clinical and demographic characteristics of the condition, a renewed interest in treatment development emerged through collaborations between international experts, industry and regulatory agencies. These efforts led to the performance of robust, high-quality clinical trials of novel therapies that targeted putative pathogenic pathways, leading to the approval of more than 10 novel therapies that have beneficially impacted both the quality and duration of life. However, our understanding of PAH remains incomplete and there is no cure. Accordingly, efforts are now focused on identifying novel pathogenic pathways that may be targeted, and applying more rigorous clinical trial designs to better define the efficacy of these new potential treatments and their role in the management scheme. This article, prepared by a Task Force comprised of expert clinicians, trialists and regulators, summarises the current state of the art, and provides insight into the opportunities and challenges for identifying and assessing the efficacy and safety of new treatments for this challenging condition.

Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement.

BACKGROUND: Right ventricular (RV) adaptation to acute and chronic pulmonary hypertensive syndromes is a significant determinant of short- and long-term outcomes. Although remarkable progress has been made in the understanding of RV function and failure since the meeting of the NIH Working Group on Cellular and Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at many levels in the understanding of cellular and molecular mechanisms of RV responses to pressure and volume overload, in the validation of diagnostic modalities, and in the development of evidence-based therapies. METHODS: A multidisciplinary working group of 20 international experts from the American Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well as external content experts, reviewed the literature, identified important knowledge gaps, and provided recommendations. RESULTS: This document reviews the knowledge in the field of RV failure, identifies and prioritizes the most pertinent research gaps, and provides a prioritized pathway for addressing these preclinical and clinical questions. The group identified knowledge gaps and research opportunities in three major topic areas: 1) optimizing the methodology to assess RV function in acute and chronic conditions in preclinical models, human studies, and clinical trials; 2) analyzing advanced RV hemodynamic parameters at rest and in response to exercise; and 3) deciphering the underlying molecular and pathogenic mechanisms of RV function and failure in diverse pulmonary hypertension syndromes. CONCLUSIONS: This statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology.

A Review of Clinical Trial Endpoints of Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension and How They Relate to Patient Outcomes in the United States.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are subgroups of pulmonary hypertension and are considered rare diseases. Understanding how endpoints of clinical trials (and patient registry studies) of patients with PAH and CTEPH are associated with patient outcomes is important in order to address the concerns of patients, health care providers, decision makers, and payers. The purpose of this review was to examine how endpoints used in clinical trials and patient registry studies are associated with outcomes of patients with PAH and CTEPH. A PubMed literature search was conducted to retrieve published studies, including randomized phase III clinical trials and observational studies, from years 2000 to May 2015 that evaluated the associations between change in 6-minute walking distance (6MWD), 6MWD thresholds, change in World Health Organization functional class (WHO-FC), and time to clinical worsening with outcomes of patients with PAH and CTEPH. Based on this review of published literature, a reduction in 6MWD as a criterion for PAH worsening, a deterioration in WHO-FC, and delay in the time to clinical worsening are clinically meaningful trial endpoints and are associated with outcomes of patients with PAH and CTEPH. Utilization and standardization of these endpoints will be useful for comparing interventions of clinical trials and therapies. Hospitalizations are frequent among patients with PAH and CTEPH, and total health care costs are high. From a U.S. payer perspective, clinical worsening is an important composite endpoint in that it includes hospitalization, which can be transformed into a preventative cost value associated with efficacious treatment of patients with PAH and CTEPH. In view of the greater number of medications available to treat PAH, the introduction of the first approved therapy to treat CTEPH, and the increasing use of combination pharmacotherapy, reliable prognostic markers of treatment responsiveness are important to help guide appropriate management. As new clinical trials and observational studies are conducted, it will be important to maintain universal endpoints so that health care providers, decision makers, and payers can better understand the value of targeted pharmacotherapies and combination therapies for the treatment of patients with PAH and CTEPH. DISCLOSURES: Sponsorship for this review and article processing charges were funded by Bayer HealthCare Pharmaceuticals. Divers and Platt are employees of Bayer HealthCare Pharmaceuticals. Wang is an employee of Bayer HealthCare Pharmaceuticals and owns stock in the company. Lin and Lingohr-Smith are employees of Novosys Health, which received research funds from Bayer HealthCare Pharmaceuticals in connection with conducting this review and developing this manuscript. Mathai is a consultant to Bayer HealthCare Pharmaceuticals and also reports consulting fees from Actelion and Gilead. Study concept and design were contributed by Divers, Platt, Lin, and Mathai. Lin and Lingohr-Smith collected the data, and data interpretation was performed by Divers, Platt, Wang, and Matthai. The manuscript was written primarily by Lingohr-Smith, with assistance from the other authors, and revised by Divers, Platt, Wang, and Mathai.

Health-related Quality of Life and Survival in Pulmonary Arterial Hypertension.

RATIONALE: Pulmonary arterial hypertension is a progressive disease with high morbidity and mortality despite advances in medical therapy. The relationship between patient-related outcomes, such as health-related quality of life (HRQOL), and survival is not well described. OBJECTIVE: To assess the relationship between HRQOL and outcomes in patients with pulmonary arterial hypertension. METHODS: Consecutive patients with right heart catheterization-proven pulmonary arterial hypertension who completed the Medical Outcomes Survey Short Form-36 survey (SF-36) were included. Demographic, clinical, physiological, and hemodynamic data were collected at baseline. Survival was assessed from the time of diagnosis of pulmonary arterial hypertension. Cox proportional hazard models were constructed to assess the relationship between HRQOL and transplant-free survival. MEASUREMENTS AND MAIN RESULTS: Eighty-seven patients with pulmonary arterial hypertension were enrolled and followed prospectively for a median of 3.8 years. At baseline, HRQOL was significantly worse than U.S. normal values for six of eight domains of the SF-36. Several domains demonstrated moderate correlation (r value ≥ 0.40) with 6-minute-walk distance and World Health Organization functional class; there were no significant associations with hemodynamics. In univariable Cox proportional hazard models, six of eight domains and both summary scores were significantly associated with survival. In multivariable models, adjusted for age, disease type, and cardiac function, these relationships largely persisted. CONCLUSIONS: In this cohort of patients with pulmonary arterial hypertension, HRQOL, as assessed by the SF-36, was strongly associated with transplant-free survival. These relationships persisted when controlling for potential confounders such as disease type and disease severity. These findings suggest that HRQOL may be an important predictor of outcomes in pulmonary arterial hypertension and therefore a target for future therapeutic interventions.

The cost to managed care of managing pulmonary hypertension.

OBJECTIVE: To estimate direct medical costs and resource use for commercially-insured patients within two pulmonary hypertension sub-groups: pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). RESEARCH DESIGN AND METHODS: Using a retrospective cohort design, subjects (≥18 years) with ICD-9 code 416.0 (PAH or CTEPH) or 416.8 (CTEPH) were identified during 2004-2009 within the MarketScan database. The date of the first observed claim was the index date. Each PAH and CTEPH patient was matched to one-to-five controls without PAH and CTEPH on age, gender, region, and payer type. Patients and controls were continuously enrolled for at least 12 months pre- and 12 months post-index date. Per-patient-per-month costs and resource use were compared using Wilcoxon rank-sum test. RESULTS: PAH patients (1647) and controls (6352) were identified (mean age 63 years, 73% female). Total monthly costs before PAH diagnosis were: PAH patients $2064 vs controls $1094. After PAH diagnosis, PAH patients had significantly higher monthly costs and resource use vs controls: Total costs $4021 vs $1533, outpatient visits 1.1 vs 0.8, inpatient visits 0.7 vs 0.2, prescriptions 3.6 vs 2.7, all p-values <0.05. One hundred and forty-six CTEPH patients and 558 controls were identified (mean age 64 years, 54.8% female). Total monthly costs in the period before CTEPH diagnosis were higher for CTEPH patients ($3895) than controls ($1177). After CTEPH diagnosis, CTEPH patients had significantly higher monthly costs and resource use vs controls: Total costs $6198 vs $1579, Outpatient visits 1.2 vs 0.8, inpatient visits 2 vs 0.2, prescriptions 4.2 vs 2.8, all p-values <0.05. KEY LIMITATIONS: Identification of PAH is complicated, as there exists no precise ICD-9-CM code for the condition. CTEPH diagnosis was based upon claims data and was not verified clinically. CONCLUSIONS: CTEPH and PAH patients incurred higher costs and used more resources than controls in the baseline and follow-up periods.

Increased right ventricular Septomarginal trabeculation mass is a novel marker for pulmonary hypertension: comparison with ventricular mass index and right ventricular mass.

OBJECTIVE: : To prospectively evaluate the cardiac magnetic resonance (MR) imaging-derived measurement of right ventricular (RV) septomarginal trabeculation (SMT) mass as a noninvasive marker for pulmonary hypertension (PH), compared with the ventricular mass index (VMI = RV mass/left ventricular mass) and RV mass. MATERIALS AND METHODS: : A total of 49 patients (60 ± 12 years; 35 female) with suspected PH underwent cardiac MR and right heart catheterization on the same day. Eighteen normal volunteers were also included. The performance of SMT mass, VMI and RV mass measurement, with regard to PH detection, was analyzed using receiver operating characteristic curves. Logistic regression analysis was used to assess the association between SMT mass, RV mass, VMI, and PH. RESULTS: : The area under the receiver operating characteristic curve for SMT mass/body surface area (BSA), VMI, and RV mass/BSA in diagnosing the presence or absence of PH was 0.88, 0.87, and 0.73 respectively. In multivariable models, both SMT mass/BSA (P = 0.005, odds ratio: 8.6) and VMI (P = 0. 012, odds ratio: 1.1) were found to be significant, independent predictors of PH. CONCLUSION: : Compared with right heart catheterization measurement, SMT mass and VMI are reproducible and noninvasive MR imaging markers for the diagnosis of PH.