Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire: feasibility of utilizing one-day versus seven-day symptom reporting.
ABSTRACT: Patient-reported outcomes are important measures to include in pulmonary arterial hypertension clinical trials but are not widely utilized in clinical practice. Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) is the only pulmonary arterial hypertension-specific patient-reported outcomes instrument developed and validated in accordance with the US Food and Drug Administration guidance on patient-reported outcomes development. The PAH-SYMPACT tool measures pulmonary arterial hypertension-related symptoms and impact of pulmonary arterial hypertension on daily life. Symptoms are reported each day for seven consecutive days, and the impact of pulmonary arterial hypertension over one week is recalled and reported on day 7; however, daily symptom reporting may overburden patients and healthcare resources, limiting the practicality of PAH-SYMPACT outside of clinical trials. To determine the practicability of an abridged version of PAH-SYMPACT for which all reporting is completed on one day, symptom data from the SYMPHONY trial (NCT01841762; PAH-SYMPACT validation study) were retrospectively analyzed to assess whether symptoms reported on each day correlated with the weekly average and whether one-day symptom scores were sensitive to disease severity. Correlation coefficients comparing the weekly average and individual day symptom scores were mostly high or very high regardless of the day they were measured. Findings were similar when using either Spearman's rank correlation or weighted kappa method. One-day symptom scores differentiated well between World Health Organization functional classes II and III/IV pulmonary arterial hypertension and were sensitive to change in disease severity as measured by the Patient Global Assessment of Disease Severity. These data suggest that the one-day PAH-SYMPACT is feasible and appropriate for routine implementation in clinical practice.
Project description:Pulmonary arterial hypertension (PAH) is the best characterized and most studied type of pulmonary hypertension, classified as Group I according to the international guidelines, and hemodinamically defined as pre-capillary pulmonary hypertension. Our analysis was focused on the role of the osteopontin gene in the transcriptional profile of PAH. We used microarray to identifiy the gene expression profiles in patients with PAH and in normal controls. Overall design: Fresh frozen lung samples were obtained from the recipients organs of 15 patients with PAH and 11 normal controls (normal lung tissue obtained from tissue flanking lung cancer resections). The PAH group included 6 patients with idiopathic PAH, 4 patients with PAH secondary to connective tissue disease (CTD), 4 patients with PAH secondary to congenital heart disease (CHD) and 1 patient with chronic thromboembolic pulmonary hypertension (CTEPH). RNA was extracted and hybridized on Affymetrix microarrays.
Project description:Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder. Despite the emergence of effective therapy, PAH is commonly at an advanced stage when recognized. Factors associated with a prolonged symptomatic period before the recognition of PAH have not been fully evaluated.The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) enrolled 2,967 US adult patients with PAH from March 2006 to September 2007. Patients were considered to have delayed disease recognition if > 2 years elapsed between symptom onset and the patient receiving a PAH diagnosis, starting on PAH-specific therapy, or receiving a diagnosis by right-sided heart catheterization.In 21.1% of patients, symptoms were experienced for > 2 years before PAH was recognized. Patients with onset of PAH symptoms before age 36 years showed the highest likelihood of delayed disease recognition (OR, 3.07; 95% CI, 2.03-4.66). History of obstructive airways disease (OR, 1.93; 95% CI, 1.5-2.47) and sleep apnea (OR, 1.72; 95% CI, 1.33-2.22) were independently associated with delayed PAH recognition. Six-minute walk distance < 250 m (OR, 1.91; 95% CI, 1.16-3.13), right atrial pressure < 10 mm Hg (OR, 1.77; 95% CI, 1.26-2.48), and pulmonary vascular resistance < 10 Wood units (OR, 1.28; 95% CI, 1.02-1.60) were also associated with delayed disease recognition, but sex, race/ethnicity, and geographic region showed no association.One in five patients in the REVEAL Registry who were diagnosed with PAH reported symptoms for > 2 years before their disease was recognized. Younger individuals and patients with histories of common respiratory disorders were most likely to experience delayed PAH recognition.ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.
Project description:Pulmonary arterial hypertension (PAH) is a chronic progressive devastating disease. Symptom burden might impair health-related quality of life of patients. Furthermore, treatment on this disease brings significant financial burden to patients' families. Both physiological and psychological symptoms have been reported, but limited evidence regarding the impact of PAH on patients and caregivers exists, especially the emotional issues and their association with patients' health quality. The main purpose of this study was to describe the impact of PAH on patients and their caregivers in a Chinese population.This large-scale national survey enrolled 174 participants to complete questionnaires using face-to-face semistructured interviews.PAH influenced all aspects of patients' lives including daily activities, work, emotions, and personal relationships. Both patients and caregivers reported a major impact on family finances and on their work. The majority of patients had feelings of isolation. A lack of public understanding about PAH contributes to social isolation. Most patients and caregivers would like to get information regarding PAH doctors and patient organization contacts to obtain support.This survey-based report provides information regarding the way and extent to which PAH impacts both patients and their caregivers and provides some means for comparison with non-Chinese populations. It is important for physicians and the community to offer more support and information for PAH patients and their families.
Project description: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.
Project description:Aberrantly remodeled vasculature in pulmonary arterial hypertension (PAH) features a prominent inflammatory cell infiltrate suggesting that immune effector cells may contribute to disease progression. Global expression studies of peripheral blood mononuclear cells (PBMCs) and whole blood have attempted to better define this inflammatory component of PAH pathobiology. Overall design: PBMCs from patients with pulmonary arterial hypertension (PAH) and gender/age matching controls were isolated from whole blood. Total RNA was extracted from PBMCs and gene expression was assessed using the Affymetrix GeneChip Human Gene 1.0 ST Array
Project description:<h4>Background</h4>Pulmonary edema may complicate the use of pulmonary arterial hypertension (PAH)-targeted therapies. We aimed to determine the proportion of patients who develop pulmonary edema after initiation of parenteral prostacyclin therapy, to identify its risk factors, and to assess its implications for hospital length of stay and mortality.<h4>Methods</h4>A retrospective cohort study of patients with PAH at the initiation of parenteral prostacyclin between 1997 and 2015 enrolled in the Cleveland Clinic PAH registry. Pulmonary edema was defined as at least one symptom or clinical sign and radiographic evidence of pulmonary edema. We determined patient characteristics predictive of pulmonary edema as well as the association between pulmonary edema and hospital length of stay (LOS) and 6-month mortality.<h4>Results</h4>One hundred and fifty-five patients were included (median age, 51 years; female, 72%; white, 85%; idiopathic, 64%; and connective tissue disease [CTD], 23%). Pulmonary edema developed in 33 of 155 patients (21%). Independent predictors of pulmonary edema were high right atrial pressure (RAP), CTD etiology, and the presence of three or more risk factors for left heart disease (LHD). Pulmonary edema was associated with a 4.5-day increase in hospital LOS (95% CI, 1.4-7.5 days; P < .001) and a 4-fold increase in 6-month mortality (OR, 4.3; 95% CI, 1.28-14.36; P = .031).<h4>Conclusions</h4>Pulmonary edema occurred in 21% of patients with PAH initiated on parenteral prostacyclin. Three or more risk factors for LHD, CTD-PAH, and a high baseline RAP were independent predictors of pulmonary edema. Pulmonary edema was associated with a prolonged hospital LOS and increased 6-month mortality.
Project description:The current treatment of pulmonary arterial hypertension (PAH) uses vasodilator drugs. Although they improve symptoms associated with PAH, their chronic effects on the pulmonary vasculature and the right ventricle (RV) in humans remain unknown. We report the autopsy findings from a patient with idiopathic PAH treated with epoprostenol successfully for 18 years. The patient died of colon cancer. The pulmonary vasculature surprisingly showed extensive changes of a proliferative vasculopathy. Immunohistochemical studies confirmed ongoing cellular proliferation. Studies of the RV demonstrated concentric hypertrophy with seemingly preserved contractility. The myocardium shifted to glycolytic metabolism. Although the long-term use of epoprostenol contributed to the patient's increased survival, it did not prevent progression of the underlying vascular disease. Remarkably, the RV was able to sustain a normal cardiac output in the face of advanced vascular pathology. The mechanisms by which the RV adapts to chronic PAH need further study.
Project description:Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. Global profiles were determined in human lung tissue and compared across 11 normal and 12 severe pulmonary arterial hypertension patients. Using a combination of microarray and high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung.
Project description:Pulmonary veno-occlusive disease (PVOD) is a rare and fatal cause of pulmonary arterial hypertension (PAH). Different from other types of PAH, PVOD patients have a dismal prognosis because of the progressive nature of pulmonary vascular involvement and fatal pulmonary edema induced by PAH-targeted drugs. Lung transplantation is the only choice for these patients. In a recent article published in the journal, Yang and his colleagues found pulmonary edema was not demonstrated in 2 of the 6 PVOD patients injected with prostacyclin analogues (a kind of PAH-targeted drug). Regretfully, none of these 6 patients underwent microscopic examination of lung tissues. Here, we reported a sporadic PVOD patient evidenced by pathology and EIF2AK4 biallelic mutation. The patient was followed over the course of 3 years in our center. During the 3 years, he was admitted into our hospital for many times for the acute exacerbation of pulmonary hypertension. However, after treatment with many kinds of PAH-targeted drugs, the pulmonary hypertension was in control and he feel better every time. The present patient displayed different treatment response comparing with previous reports. It suggests that PVOD is a heterogeneity population and different patients have different characteristics including clinical manifestation, genomics, treatment response et al. How to pick off this portion of patients timely is the core issue. Lots of important works are necessary to answer this question. However, we can see a glimmer of hope form this patient at least.
Project description:Riociguat is a novel soluble guanylate cyclase stimulator that is approved for the treatment of patients with pulmonary arterial hypertension (PAH) and patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA). As riociguat is a relatively new drug, experience of its use in clinical practice is limited, especially in patients who would not have met the inclusion criteria for the pivotal Phase III clinical trials, PATENT-1 and CHEST-1. This article shares our initial practical and clinical experience in switching patients with PAH and CTEPH from the phosphodiesterase type-5 inhibitor sildenafil to riociguat, based on three selected case reports of patients who discontinued sildenafil therapy owing to side effects or disease progression (one patient with idiopathic PAH and two patients with persistent/recurrent CTEPH after PEA). Two cases illustrate our experience with direct switch from sildenafil to riociguat (6-8 h between the last sildenafil dose and the first riociguat dose), and one case illustrates switch to riociguat in a patient who underwent treatment with other PAH-specific therapies between stopping sildenafil and starting riociguat. Symptoms improved with riociguat therapy in two cases; in the third case the patient experienced worsening symptoms 1 month after initiating riociguat and was switched back to sildenafil. These case experiences contribute practical information to assist clinicians in the switch from sildenafil to riociguat therapy in patients with PAH or CTEPH.