Using PAH-SYMPACT to assess quality of life in patients with pulmonary hypertension associated with chronic lung disease.

Chronic lung disease (CLD) is the second leading cause of pulmonary hypertension (PH) and is associated with significant morbidity and mortality. Although PH associated with CLD (PH-CLD) leads to impaired health-related quality of life (HRQOL), there are no validated tools to assess HRQOL in PH-CLD. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) is an HRQOL instrument aimed at assessing the symptoms and impact of PH on overall function and well-being. We performed a single-center prospective cohort study using PAH-SYMPACT scores to compare symptoms, exercise capacity and HRQOL in patients with PAH and PH-CLD. One hundred and twenty-five patients (99 patients with idiopathic/heritable PAH and 26 with PH-CLD) completed the PAH-SYMPACT questionnaire which consists of 22 questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive/emotional (CE) impact. Higher scores indicate worse HRQOL. We compared patients with PAH and PH-CLD using a Wilcoxon rank sum or chi-squared test as appropriate. Multivariate linear regression analysis was used to assess the relationship between PH classification and SYMPACT scores. Compared to PAH, patients with PH-CLD were older, more likely to use oxygen and had worse functional class and exercise capacity. While there was no significant difference between the two groups in CP, CV, or CE domain scores, patients with PH-CLD had significantly worse PI scores by univariate (1.79 vs. 1.13, p < 0.001) and multivariate analysis (1.61 vs. 1.17, p = 0.02) and overall worse SYMPACT scores (1.19 vs. 0.91, p = 0.03). In conclusion, patients with PH-CLD have worse HRQOL as assessed by the PAH-SYMPACT questionnaire versus patients with PAH. Although PAH-SYMPACT has not been validated in PH-CLD, the results of this study can guide clinicians in understanding the symptoms and impact of PH-CLD relative to PAH.

The feasibility and value of assessing patient-reported outcomes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that negatively impacts health-related quality of life (HRQOL). The PAH-symptoms and impact (PAH-SYMPACT) questionnaire is a validated disease-specific patient-reported outcome (PRO) instrument that assesses a patient's symptoms and the impact of PAH and its treatment on well-being. We performed a single-center prospective cohort study of patients with PAH to determine the feasibility of assessing PROs in clinical practice and to determine the association between PAH-SYMPACT domains and clinical characteristics and outcomes. One hundred and ten patients completed the 1-day version of the PAH-SYMPACT questionnaire which consists of 22 Likert-scale questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive and emotional (CE) impact. Higher scores indicate worse HRQOL. Patients were predominantly female (n = 86, 78%) with a mean age of 57.8 ± 16.2 years. While several patient characteristics were associated with CP and PI domains, few were associated with CV and CE domains. PI and CE impact scores were associated with recent hospitalizations and mortality and CE impact score was independently associated with an increased risk of death after adjustment for disease severity (hazard ratio: 3.29, 95% confidence interval: 1.56-6.91, p = 0.002). In conclusion, the assessment of PROs in clinical practice using the PAH-SYMPACT questionnaire is both feasible and valuable. PAH-SYMPACT scores have independent prognostic value and are not adequately reflected by traditional measures of disease severity. These findings underscore the importance of assessing HRQOL in clinical practice.

Totally Implantable IV Treprostinil Therapy in Pulmonary Hypertension Assessment of the Implantation Procedure.

BACKGROUND: Prostacyclins improve symptoms and survival in pulmonary arterial hypertension (PAH). In response to risks associated with external delivery systems, an implantable IV infusion system was developed. A multicenter, prospective, single-arm, clinical trial (DelIVery for PAH) was conducted to evaluate this system for treprostinil in PAH. This analysis describes the findings related to the implant procedure. METHODS: Patients (N = 64) with PAH (World Health Organization group 1) receiving stable IV treprostinil were enrolled. Patients were transitioned to a temporary peripheral IV infusion catheter prior to the procedure. System implantation was performed at 10 centers under general anesthesia or deep IV sedation by clinicians from various specialties. Central venous access was via the cephalic, subclavian, jugular, or axillary vein. Using an introducer and fluoroscopic guidance, the distal tip of the infusion catheter was placed at the superior caval-atrial junction. The catheter was tunneled from the venous access site to an abdominal subcutaneous pocket, where the pump was placed. RESULTS: Of the 64 patients enrolled, four exited prior to implantation. All 60 implant procedures were successful. At baseline, all patients were receiving treprostinil via an external pump at a mean dose of 71.4 ± 27.8 ng/kg/min (range: 22-142 ng/kg/min). The implant averaged 102 ± 32 min (range: 47-184 min). Clinically significant implant procedure-related complications included one pneumothorax, two infections, and one episode of atrial fibrillation. There were three postimplantation catheter dislocations in two patients. Common implant-related events that were not complications included implant site pain (83%) and bruising (17%). CONCLUSIONS: The procedure for inserting a fully implantable system for treprostinil was successfully performed, with few complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01321073; URL: www.clinicaltrials.gov.

Characterization of Prostacyclin-associated Leg Pain in Patients with Pulmonary Arterial Hypertension.

RATIONALE: Prostacyclin-associated leg pain is a potentially debilitating adverse effect of prostacyclin therapy for patients with pulmonary arterial hypertension (PAH). However, to our knowledge, this entity has not been systematically studied. OBJECTIVES: To characterize the clinical features and metabolic risk factors for prostacyclin-associated leg pain. METHODS: At one academic medical center, we assembled and analyzed a case series of patients with PAH and prostacyclin-associated leg pain. MEASUREMENTS AND MAIN RESULTS: Over a period of 2 years, we identified 11 patients with PAH and prostacyclin-associated leg pain who agreed to participate in this study. Subjects underwent a standardized clinical evaluation, electrodiagnostic assessment, and serologic screen for metabolic causes of peripheral neuropathy. All 11 patients were female; their mean (SD) age was 50 (±9) years; their median (interquartile range) PAH duration was 56 (20-96) months; and their prostacyclin therapy duration was a median (interquartile range) of 20 (14-36) months. All patients reported leg pain beginning soon after prostacyclin initiation and varying with dose. All described a neuropathic pain in a symmetric, distal, stocking distribution. Neurologic examination revealed a sensory, small-fiber, predominantly peripheral neuropathy in seven (78%) patients. Results of autonomic reflex testing and thermoregulatory sweat testing were abnormal in 82% and 90% of patients, respectively, suggesting small-fiber neuropathy. Serologic evaluation identified a new, previously unrecognized contributor to neuropathy in eight (73%) patients, including vitamin B12 deficiency in six (55%), uncompensated hypothyroidism in three (27%), and diabetes mellitus in one (9%). CONCLUSIONS: Chronic prostacyclin-associated leg pain is associated with a small-fiber neuropathy. Treatable metabolic contributors (vitamin B12 deficiency, thyroid dysfunction, or diabetes) appear to be common possible "second hits" that may be underrecognized. We recommend screening for possible metabolic contributors in patients who have otherwise unexplained leg pain in the setting of PAH and current or anticipated prostacyclin therapy.

Conversion from sildenafil to tadalafil: results from the sildenafil to tadalafil in pulmonary arterial hypertension (SITAR) study.

PURPOSE: Among phosphodiesterase type 5 inhibitors, tadalafil offers clinicians a once-daily alternative to 3 times daily sildenafil for the treatment of pulmonary arterial hypertension (PAH). This study assessed the safety and patient satisfaction with conversion from sildenafil to tadalafil. METHODS: In this multicenter, prospective, 6-month study, patients with PAH were instructed to take their last dose of sildenafil in the evening and initiate tadalafil 40 mg/d the next morning. Patients completed the Treatment Satisfaction Questionnaire for Medication at baseline and 30, 90, and 180 days after transition to assess PAH symptoms and patient satisfaction. Safety was assessed on the basis of recorded adverse events (AEs). RESULTS: Of the 35 patients who met the study criteria, 56% were receiving ≥2 PAH therapies. At the time of transition, the sildenafil dose ranged from 40 to 300 mg/d, with 20% of the patients on >20 mg of sildenafil 3 times daily. Transition to tadalafil was generally well tolerated, and the incidence of common AEs, except for myalgia, appeared to decrease over time on tadalafil therapy. Five (14%) patients switched back to sildenafil. A greater percentage of patients were satisfied than were dissatisfied after conversion to tadalafil (55% vs 19% at 90 days), while 26% felt about the same degree of satisfaction. Conversion to tadalafil resulted in significant improvement in patient ratings of therapy convenience. CONCLUSIONS: Transition of patients from sildenafil to tadalafil was usually well tolerated, with improved convenience and may enhance treatment satisfaction.

Physician attitudes toward palliative care for patients with pulmonary arterial hypertension: results of a cross-sectional survey.

Pulmonary arterial hypertension (PAH) is a chronic, symptomatic, life-threatening illness; however, it is complex, with variable expression regarding impact on quality of life (QOL). This study investigated attitudes and comfort of physicians regarding palliative care (PC) for patients with PAH and explored potential barriers to PC in PAH. An internet-based, mixed-methods survey was distributed to Pulmonary Hypertension Clinicians and Researchers, a professional organization within the Pulmonary Hypertension Association. Only responses from physicians involved in clinical care of patients with PAH were analyzed. Of 355 clinicians/researchers, 79 (22%) returned surveys, including 76 (21%) providers involved in clinical care. Responding physicians were mainly pulmonologists (67%), practiced in university/academic medical centers (89%), had been in practice a mean of 12 ± 7 years, cared for a median of 100 PAH patients per year, and reported a high level of confidence in managing PAH (87%), advanced PAH-specific pharmacologic interventions (95%), and end-of-life care (88%). Smaller proportions were comfortable managing pain (62%) and QOL issues (78%). Most physicians (91%) reported utilizing PC consultation at least once in the prior year, primarily in the setting of end-of-life/active dying (59%), hospice referral (46%), or symptomatic dyspnea/impaired QOL (40%). The most frequent reasons for not referring patients to PC included nonapproval by the patient/family (51%) and concern that PC is "giving up hope" (43%). PAH may result in symptoms that impair QOL despite optimal PAH therapy; however, PC awareness and utilization for PAH providers is low. Opportunities may exist to integrate PC into care for PAH patients.

Symptom burden, quality of life, and attitudes toward palliative care in patients with pulmonary arterial hypertension: results from a cross-sectional patient survey.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a complex disease with variable clinical manifestations; nevertheless, morbidity and mortality associated with PAH are considerable. This study examined quality of life (QOL) in PAH patients and assessed use of palliative care (PC) for addressing QOL issues and what barriers might exist regarding early PC implementation for patients with PAH. METHODS: An Internet-based survey was distributed to Pulmonary Hypertension Association patient-related listservs. Symptom burden and QOL were assessed using Linear Analog Self Assessment (LASA) QOL items and the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). RESULTS: Of 774 eligible patients with active e-mail addresses, 315 returned surveys (41% overall response), and 276 (88%) contained analyzable responses. Responders (mean age, 48.9 years ± 16.0) were predominantly white (85%), female (86%), and with idiopathic PAH (42%). Profound deficiency in overall QOL (40%), fatigue (57%), physical well-being (56%), social activity (49%), emotional well-being (49%), and pain (38%) were reported. Most patients believed their PAH physician had excellent understanding of PAH progression/plan of care (92%), but less were satisfied with care regarding QOL management (77%). Few patients considered PC (8%), or had pain management (4%) or PC involved (1%). Most common reasons were beliefs that patients were doing well/not sick (63%) or that PC had not been suggested (22%). CONCLUSIONS: PAH may result in symptoms or QOL impairment persisting despite optimal PAH therapy. However, PC awareness or use by PAH patients and providers is low. Opportunities may exist to integrate PC into care for PAH patients.

Impact of the removal of the monthly liver function test requirement for ambrisentan.

BACKGROUND: The management of patients with pulmonary arterial hypertension (PAH) requires extensive coordination between patients, their support system, third-party payers, and healthcare professionals. For patients with PAH who are receiving endothelin receptor antagonists (ERAs), such cross-stakeholder coordination was needed to ensure compliance with a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) requirement for monthly liver function tests (LFTs). In March 2011, the FDA removed this requirement for ambrisentan (Letairis) in conjunction with a change to the product label. OBJECTIVE: This study sought to explore the impact of the ambrisentan label change on payers, providers who treat PAH, and specialty pharmacies. METHODS: This study, conducted in June and July 2011, involved telephone interviews with 5 medical/pharmacy directors in commercial health plans (representing 78,345,000 covered lives collectively); written surveys and telephone interviews with 6 nurses managing patients with PAH; and written surveys and telephone interviews with 4 staff members from specialty pharmacies to determine direct and indirect cost-savings associated with the removal of the monthly LFT requirement for ambrisentan. Qualitative telephone interviews with payer decision makers informed the cost-savings for payers. Direct cost-savings were calculated from the responses of the nurses managing PAH regarding the prescribing trends of their practices and the frequency of LFTs. Indirect cost-savings were calculated using time-savings data collected from the PAH-managing nurses and the specialty pharmacy staff, as well as from the US Bureau of Labor Statistics data regarding national wage averages for the respective staff. RESULTS: Payers reported that REMS requirements did not play a large role in their plan's coverage or management of ERAs; although direct cost-savings resulting from the label change were an estimated $28 per patient per month, this amount is relatively small compared with the overall cost of PAH treatment for payers. The impact of the ambrisentan label change was more significant for providers and specialty pharmacies. The label change resulted in a significant, average 69% reduction in the frequency of LFTs for patients using ambrisentan. The average monthly time-savings realized by providers as a result of the label change was 12 minutes per patient receiving ambrisentan, and the average monthly direct and indirect cost-savings totaled $10.75 and $29.75, respectively, per patient taking ambrisentan. Telephone interviews with specialty pharmacies indicated that the average monthly time-savings for the 4 specialty pharmacies surveyed was 14 minutes per patient using ambrisentan, representing an 86.7% decrease in the amount of time specialty pharmacies spent on LFT-related administrative tasks for patients using ambrisentan. CONCLUSION: Findings from this study indicate that the ambrisentan label change significantly reduced the number of LFTs for patients with PAH, resulting in time-savings or cost-savings for payers, providers, and specialty pharmacies.

Immediate and long-term hemodynamic and clinical effects of sildenafil in patients with pulmonary arterial hypertension receiving vasodilator therapy.

OBJECTIVE: To determine the immediate and long-term effects of adding sildenafil, a phosphodiesterase-5 inhibitor, to the medical regimen of patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: Thirteen patients with PAH received empirical adjunctive sildenafil treatment at the Mayo Clinic in Rochester, Minn, between November 1, 2000, and August 31, 2001. All received a 25-mg dose of sildenafil, increased by 25 mg at 8-hour intervals, if tolerated, up to 100 mg during hemodynamic monitoring for 24 to 48 hours. Long-term effects on right heart hemodynamics were assessed by noninvasive right ventricular systolic pressure, right ventricular index of myocardial performance, and a 6-minute walk test. RESULTS: Sildenafil significantly increased cardiac output (CO) (P = .04) and decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and mean arterial pressure (P < or = .01) at peak measurements (obtained 1-2 hours after highest dose). At trough measurements (obtained 8 hours after highest dose), sildenafil significantly decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, and mean arterial pressure (P = .01). Ten patients discharged from the hospital were taking the highest-tolerated dose of sildenafil every 8 hours. The right ventricular systolic pressure and right index of myocardial performance showed no significant improvement at follow-up (117 +/- 70 days), although concomitant treatment with epoprostenol could be tapered in 2 patients. Changes in New York Heart Association classes were inconsistent, and improvements in the 6-minute walk test were not significant. CONCLUSION: Sildenafil has an immediate pulmonary vasodilator effect in patients already receiving vasodilators for PAH. Its long-term effects on right heart function and functional status are equivocal. A large, prospective, well-designed study is needed to determine the effects of sildenafil on PAH, both in untreated and concurrently treated patients.