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World Health Organization functional classification (WHO FC) definitions 

World Health Organization functional classification (WHO FC) definitions 

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Article
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Pulmonary arterial hypertension (PAH) is a severe, progressive condition of the small pulmonary vessels that leads to increased pulmonary vascular resistance, right ventricular failure and death. Patients in World Health Organization functional class (WHO FC) IV are the most severely affected in terms of disease severity, symptomatic impairment, ex...

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... WHO functional classes range from I-IV, the higher the functional class the more symptomatic. 24,25 Echocardiograms were analyzed at the Center for Quantitative Echocardiography. All measurements were performed using the American Society of Echocardiography guidelines. ...
Article
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Women with pulmonary arterial hypertension (PAH) experience multiple symptoms, including dyspnea, fatigue and sleep disturbance, that impair their health‐related quality of life (HRQOL). However, we know little about phenotypic subgroups of patients with PAH with similar, concurrent, multiple symptoms. The objectives of this study were to define the “symptome” by symptom cluster phenotypes and compare characteristics such as biomarkers, cardiac structure and function (echocardiography), functional capacity (6‐minute walk distance) and HRQOL between the groups. This cross sectional study included 60 women with PAH. Subjects completed an assessment battery: Pulmonary Arterial Hypertension Symptom Scale (PAHSS), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Dyspnea Profile (MDP), Patient‐Reported Outcomes Measurement Information System (PROMIS®) Physical Function, PROMIS® Sleep‐Related Impairment and the EmPHasis 10. Subjects also underwent transthoracic echocardiography, phlebotomy, 6‐minute walk distance and actigraphy. The three symptoms of dyspnea, fatigue, and sleep disturbance were used to define the symptom clusters. Other PAH symptoms, plasma and serum biomarkers, cardiac structure and function (echocardiography), exercise capacity (6‐minute walk distance), sleep (actigraphy) and HRQOL were compared across phenotypes. The mean age was 50 +18 years, 51% were non‐Hispanic white, 32% were non‐Hispanic Black and 40% had idiopathic PAH. Cluster analysis identified Mild (n= 28, 47%), Moderate (n= 20, 33%), and Severe Symptom Cluster Phenotypes(n= 12, 20%). There were no differences for age, race or PAH etiology between the phenotypes. WHO functional class (P<0.001), norepinephrine levels (P=0.029), right atrial pressure (P=0.001), physical function (P<0.001), sleep onset latency (P=0.040) and HRQOL (P<0.001) all differed significantly across phenotypes. We identified three distinctive symptom cluster phenotypes (Mild, Moderate and Severe) for women with PAH that also differed by PAH‐related symptoms, physical function, right atrial pressure, norepinephrine levels and HRQOL. These phenotypes could suggest targeted interventions to improve symptoms and HRQOL in those most severely affected. This article is protected by copyright. All rights reserved.
... Seventy-five percent of participants had at least some college education. Mean (SD) time since diagnosis of CTEPH was 4.2 (3.7) years, and half of the participants had a World Health Organization (WHO) functional class of II, indicating slight limitation of physical activity [18]. Most participants (n = 10) had undergone PEA and/or BPA. ...
Article
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Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension caused by blood clots and scar tissue in the blood vessels of the lungs. Health-related quality of life is often significantly impaired in patients with CTEPH. However, a better understanding of how CTEPH symptoms affect patients’ lives is needed to optimally assess the impact of the disease and treatment. Objectives This qualitative study aimed to better understand the symptoms of CTEPH and how they affect patients’ lives, as well as to determine the appropriateness of the Pulmonary Arterial Hypertension – Symptoms and Impact (PAH-SYMPACT™) questionnaire for use in this patient population. Methods Adults diagnosed with CTEPH, recruited from two clinical sites in the US, participated in one-to-one qualitative telephone interviews. They described their experience of CTEPH symptoms and the impact these symptoms have on their lives. They also provided feedback on the comprehensibility and relevance of the PAH-SYMPACT™‘s instructions, items, and response options. Results Participants ( N = 12) had a mean age of 62.5 years. Two thirds were female and most (83%) had undergone pulmonary endarterectomy and/or balloon pulmonary angioplasty. The most frequently endorsed symptoms were shortness of breath (endorsed by all 12 participants), fatigue (11 participants), and lightheadedness (10 participants). All participants identified shortness of breath as an “extremely important” symptom, and seven participants rated fatigue as “extremely important.” The most frequent impacts of CTEPH were on ability to walk quickly (endorsed by all 12 participants), ability to walk up inclines or stairs (11 participants), and ability to carry things (11 participants). The PAH-SYMPACT™ items were relevant to most participants and reflected their experience of CTEPH. All participants indicated that no important CTEPH symptoms were missing from the PAH-SYMPACT™. Overall, the instructions, items, and response options of the PAH-SYMPACT™ were clear and easy to understand. Conclusions The symptoms and impacts experienced by patients with CTEPH align with items included in the PAH-SYMPACT™. The PAH-SYMPACT™ appears to be fit for purpose for assessing disease status in patients with CTEPH.
... The World Health Organization (WHO) functional class, systolic pulmonary arterial pressure (sPAP) measured in echocardiography, sixminute walk distances (6MWD), and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were noted at the time of recruitment. WHO functional class is a scale from 1 to 4 that is used to assess the severity of pulmonary hypertension based on symptoms of dyspnea, fatigue, chest pain, and related syncope. 1 is best and 4 is the worst functional class (Vachiéry & Simonneau, 2010) and can be explained as follows: Estimation of SPAP by transthoracic doppler echocardiography was performed by an experienced cardiologist; it is based on peak tricuspid regurgitation velocity and right atrial pressure (Galiè et al., 2016). The 6MWT was performed according to the ATS/ERS criteria (ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories, 2002). ...
Article
Both quality of life (QoL) and caregiver burden are essential constructs in patients with pulmonary hypertension (PH) however; their relationship has never been investigated before. The aim of this study was to evaluate if there was any relationship between patients' QoL and caregiver burden. Patients with PH and their caregivers were included. Patients' age, sex, World Health Organization (WHO) functional class, systolic pulmonary arterial pressure (sPAP), and six-minute walk distances (6MWD) were recorded. Patients' QoL was assessed using emPHasis-10 and caregiver burden with the Zarit Caregiver Burden Scale. 72 patient-caregiver dyads were included. Caregiver burden was significantly correlated with the QoL(r = 0.39 p < .003), but was not correlated with other clinical parameters. Patients' QoL showed significant negative correlation with the 6MWD(r = -0.46 p < .005). There is a moderate correlation between QoL and caregiver burden. Clinical parameters influence QoL, but they do not affect caregiver burden.
... Furthermore, pulmonary hypertension is scored based on the severity of specific symptoms into four different World Health Organisation (WHO) functional classes [6] [7]: WHO functional class I: Patients with pulmonary hypertension, but without resulting limitation of physical activity. ...
Article
Pulmonary hypertension is a debilitating chronic disease. In the last 20 years, there has been im-pressive progress in the treatment strategy of pulmonary arterial hypertension. This led to a significant increase in the awareness and improvement in the clinical outcome, though there was no substantial improvement in the rate of mortality. This review summarizes the current state of the art of the treat-ment of pulmonary arterial hypertension, including the three main categories of pulmonary hypertension specific medication which were introduced in the last 20 years. Mainly drugs that restore prostaglandins function of the endothelial cells, drugs that restore Cyclic GMP in the endothelial cells and various forms of medication that inhibit Endothelin receptors. The current strategy to treat patients with pulmonary arterial hypertension is to initiate drug therapy as early as possible and to adopt combinational therapy using two or more classes of drugs simultaneously. There are current efforts to introduce future medica-tion that can be more specific to a phenotype of pulmonary hypertension.
... The severity of PAH is typically determined according to the classification of the World Health Organization (WHO Functional Classification (FC)) for PAH [5], which classify patients into four different classes: FC I to FC IV, where the higher classes indicates more severe disease status. When untreated, median survival is only 6 months for patients in WHO FC IV, compared with 2.5 years for those in WHO FC III, and 6 years for those in WHO FC I and II [5]. ...
... The severity of PAH is typically determined according to the classification of the World Health Organization (WHO Functional Classification (FC)) for PAH [5], which classify patients into four different classes: FC I to FC IV, where the higher classes indicates more severe disease status. When untreated, median survival is only 6 months for patients in WHO FC IV, compared with 2.5 years for those in WHO FC III, and 6 years for those in WHO FC I and II [5]. Therapies targeting the prostacyclin pathway are recommended for patients in FC II-IV [1], but their use has been limited by their mode of administration [6]: continuous parenteral administration or frequent inhaled administration (6-9 times daily) [7]. ...
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Background Pulmonary Arterial Hypertension (PAH) is a chronic rare disease that can lead to serious cardiovascular problems and death. Additional treatments that increase effectiveness, that are safe and with a convenient administration that improve outcomes and quality of life for patients are needed. The aim of this study was to assess the value contribution of the new, oral prostacyclin receptor agonist, selexipag, for PAH treatment in Spain through reflective Multicriteria Decision Analysis (MCDA) methodology. Methods A comprehensive literature review was performed to develop an evidence matrix, composed of twelve quantitative criteria and four contextual criteria, based on an EVIDEM MCDA framework adapted to orphan drugs evaluation by the Spanish region of Catalonia. Quantitative performance scores, qualitative impact of contextual criteria and individual reflections from stakeholders were collected for each MCDA framework criteria. The value contribution of selexipag to PAH treatment compared to inhaled iloprost was calculated. Results Oral selexipag for PAH treatment was considered as a treatment which adds value, compared to iloprost, in the following MCDA quantitative criteria: comparative efficacy, patient reported outcomes, preventive benefit, therapeutic benefit, other medical costs and other non-medical costs, without significant differences in safety profile but with a higher acquisition cost than inhaled iloprost. Conclusions Selexipag was considered to provide value to PAH treatment. It was perceived as an intervention indicated for a severe rare disease with high unmet needs, supported by high quality clinical evidence. When compared to inhaled iloprost, oral selexipag has demonstrated improvements in efficacy and patient reported outcomes, with a similar safety profile and some additional costs. Reflective MCDA provided a standardised, transparent approach to evaluate multiple criteria relating to the overall value contribution of selexipag to PAH treatment facilitating decision-making.
... In addition to the relationship of dyspnea and fatigue with activity limitations, the WHO functional classification (FC) incorporates syncope, as well as signs and symptoms of right heart failure. The classification system includes four classes (I, II, III, and IV), with increased PAH severity ranked as higher classes 3,4 . Table 1 shows a description of each class. ...
Article
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Background and aims: Pulmonary arterial hypertension (PAH) is a rare medical disease in which patients experience increased pulmonary vascular resistance (PVR) and pulmonary arterial pressure that can result in remodeling of the pulmonary vasculature and heart and eventually lead to right heart failure and death. As PAH progresses, patients become unable to perform even routine daily tasks without severe shortness of breath (dyspnea), fatigue, dizziness, and fainting (syncope). Treatment strategies largely depend on assessment of an individual patient’s WHO Functional Class. The aim of the present study was to determine whether PAH functional decline, as described by the WHO Functional class (FC), is associated with increased healthcare costs for patients. Methods: Patients with a prescription for a FDA-approved treatment for PAH and a medical claim indicating chronic pulmonary heart disease or right heart catheterization, were identified from an administrative claims database. Provider-reported data from prior authorization forms required for advanced PAH therapies and medical charts were examined for reported FC. Healthcare resource utilization and costs were the primary outcomes of interest. Costs were accounted in 2014 US dollars ($) from a healthcare payer perspective. Results: Patients with a reported FC-IV were observed to have the worst outcomes; averaging significantly more inpatient admissions, longer average lengths of stay and more emergency department visits than the other FC subgroups resulting in higher medical costs. Conclusions: Using administrative data to document disease severity, this study replicates and expands on findings obtained from registry study; disease severity was associated with higher healthcare resource utilization and costs. Stakeholders’ implications for patient management are discussed.
... Bosentan is a dual ERA with high affinity of both ETA and ETB receptors. Bosentan is indicated for the treatment of pulmonary artery hypertension (PAH) by blocking the action of endothelin molecule (Ohlstein & Douglas, 1993;Vachiery & Simonneau, 2010;Granton et al., 2013) and it can prevent or reverse the associated histological change caused by elevated levels of ET1. Bosentan and its metabolites are eliminated predominantly in the liver by the cytochrome P450 isoenzymes, CYP2C9, CYP3A4 and the terminal half-life after oral administration is 5.4 h (Dingemanse & van Giersbergen, 2004). ...
Article
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Bosentan is an endothelin receptor antagonist (ERA) prescribed for patients with pulmonary arterial hypertension (PAH). The oral delivery of bosentan possesses several drawbacks such as low bioavailability (about 50%), short duration of action, frequent administration, hepatotoxicity and systemic hypotension. The pulmonary administration would circumvent the pre-systemic metabolism thus improving the bioavailability and avoids the systemic adverse effects of oral bosentan. However, the short duration of action and the frequent administration are the major drawbacks of inhalation therapy. Thus, the aim of this work is to explore the potential of respirable controlled release polymeric colloid (RCRPC) for effective, safe and sustained pulmonary delivery of bosentan. Central composite design was adopted to study the influence of formulation and process variables on nanoparticles properties. The particle size, polydispersity index (PDI), entrapment efficiency (EE) and in vitro bosentan released were selected as dependent variables. The optimized RCRPC showed particle size of 420 nm, PDI of 0.39, EE of 60.5% and sustained release pattern where only 31.0% was released after 16 h. The in vitro nebulization of RCRPC indicated that PLGA nanoparticles could be incorporated into respirable nebulized droplets better than drug solution. Pharmacokinetics and histopathological examination were determined after intratracheal administration of the developed RCRPC to male albino rats compared to the oral bosentan suspension. Results revealed the great improvement of bioavailability (12.71 folds) and sustained vasodilation effect on the pulmonary blood vessels (more than 12 h). Bosentan-loaded RCRPC administered via the pulmonary route may therefore constitute an advance in the management of PAH.
... Dabei ist zu beachten, dass die Sensitivität zur Erkennung einer frühen PH von den gewählten Grenzwerten der trikuspidalen Refluxgeschwindigkeit (TRV) abhängig ist. Bei Patienten (insbesondere bei Vorliegen einer anderweitig nicht erklärbaren Dyspnoe) erscheint bei einer TRV von 2,9-3,4 m/s (entspricht etwa einem systolischen PAP von 37-50 mmHg) das Vorliegen einer PH möglich und es sollte eine invasive Kontrolle erfolgen [42]. Auch bei Unterschreiten des Grenzwertes der TRV, aber vorhandenen anderen echokardiografischen Hinweisen auf eine PH oder bei Risikogruppen für die PH (z. ...
Article
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In patients with pulmonary hypertension progressive vascular changes in the lung precede the clinical and hemodynamic manifestations of the disease. Therefore, early diagnosis and timely treatment of the disease are crucial. This has been the topic of an expert meeting in Greifswald, Germany in June 2012. The current definition of pulmonary hypertension requires a mean pulmonary artery pressure ≥ 25 mmHg at rest, a hemodynamic abnormality already reflecting pulmonary vascular changes beyond early disease. There is increasing evidence supporting the concept that a lower pressure threshold at rest or an abnormal pressure response with exercise better characterize early disease. While right heart catheterization at rest remains the diagnostic gold standard other methods for detecting early disease are explored with echocardiography being the most frequently used technique. Targeted therapy has been approved for patients with pulmonary arterial hypertension (PAH, WHO-group I) in functional class II-IV. Preliminary data in functional class I patients suggest therapeutic potential of theses drugs in early disease as well. Current guidelines propose therapeutic goals based on parameters with prognostic importance. However, these recommendations are based on mostly retrospective analyses of pre-treatment data obtained in patients with pulmonary hypertension in functional class II-IV. Therefore, evidence-based therapeutic goals for early interventions in functional class I patients are lacking. © Georg Thieme Verlag KG Stuttgart · New York.
... Pulmonary hypertension (PH) is defined as mean pulmonary artery pressure (mPAP) that exceeds 25 mmHg at rest, as measured by right heart catheterization (RHC) (1). PH can occur as an isolated condition or in association with various clinical settings, including connective tissue disease (CTDs) (2). ...
Article
Pulmonary hypertension (PH) is a rare manifestation in patients with primary Sjogren's syndrome (pSS) and it can occur with or without interstitial lung disease (ILD). Patients with PH and ILD who show signs of exacerbation of dyspnea are commonly assessed for pure PH aggravation, ILD progression or pulmonary infection. However, the presence of congenital cardiac anomalies, such as partial anomalous pulmonary vein return (PAPVR), can also be a cause of dyspnea exacerbation. PAPVR is a rare congenital anomaly that involves drainage of 1 to 3 pulmonary veins into the right-sided heart circulation, resulting in a partial left-to-right shunt. Here we present a case of PAPVR as the cause of PH aggravation in a patient with pSS with accompanying PH.
... However, as disease progresses, pulmonary arterial pressure may not rise further but CO still declines because of the high outflow impedance; in fact, this might lead to a fall in pressures . Considering, therefore, the relevance of CO for patients′ functioning and the fact that cardiac failure is the usual cause of death (Vachiéry & Simonneau, 2010), measurements of CO are considered a key end-point in this patient population . Unfortunately, however, direct haemodynamic measurements by right heart catheterization during repeated exercise tests (Fick and thermodilution methods) are not clinically feasible and might not be ethically justifiable (Deboeck et al., 2004;Provencher et al., 2008;Groepenhoff et al., 2010). ...
Article
Haemodynamic responses to exercise are related to physical impairment and worse prognosis in patients with pulmonary arterial hypertension (PAH). It is clinically relevant, therefore, to investigate the practical usefulness of non-invasive methods of monitoring exercise haemodynamics in this patient population. Using a novel impedance cardiography (ICG) approach that does not require basal impedance estimations and relies on a morphological analysis of the impedance signal (Signal-Morphology-ICG(™)), stroke volume (SV) and cardiac index (CI) were evaluated in 50 patients and 21 age-matched controls during a ramp-incremental cardiopulmonary exercise testing. Technically unacceptable readings were found in 12 of 50 (24%) patients. In the remaining subjects, early decrease (N = 9) or a 'plateau' in SV (N = 8) and Δ (peak-unloaded exercise) SV <10 ml were markers of more advanced PAH (P<0.05). ΔCI ≤ 1.5-fold and early estimated lactate threshold were the only independent predictors of a severely reduced peak oxygen uptake (VO(2)) in patients (R(2) = 0.71, P<0.001). The finding of ΔCI ≤ 1.5-fold plus peak VO(2) < 50% predicted was associated with a number of clinical and functional markers of disease severity (P<0.001). In addition, abnormal SV responses and ΔCI ≤ 1.5-fold were significantly related to 1-year frequency of PAH-related adverse events (death and balloon atrial septostomy, N = 8; P<0.05). 'Qualitative' and 'semi-quantitative' signal-morphology impedance cardiography(™) (PhysioFlow(™)) during incremental exercise provided clinically useful information to estimate disease severity and short-term prognosis in patients with PAH in whom acceptable impedance signals could be obtained.