Clinical Classification Of Pulmonary Hypertension Research Articles

Phenotypes in Pulmonary Hypertension.

The clinical classification of pulmonary hypertension (PH) has guided diagnosis and treatment of patients with PH for several decades. Discoveries relating to underlying mechanisms, pathobiology, and responses to treatments for PH have informed the evolution in this clinical classification to describe the heterogeneity in PH phenotypes. In more recent years, advances in imaging, computational science, and multi-omic approaches have yielded new insights into potential phenotypes and sub-phenotypes within the existing clinical classification. Identification of novel phenotypes in pulmonary arterial hypertension (PAH) with unique molecular profiles, for example, could lead to new precision therapies. Recent phenotyping studies have also identified groups of patients with PAH that more closely resemble patients with left heart disease (group 2 PH) and lung disease (group 3 PH), which has important prognostic and therapeutic implications. Within group 2 and group 3 PH, novel phenotypes have emerged that reflect a persistent and severe pulmonary vasculopathy that is associated with worse prognosis but still distinct from PAH. In group 4 PH (chronic thromboembolic pulmonary disease) and sarcoidosis (group 5 PH) the current approach to patient phenotyping integrates clinical, hemodynamic and imaging characteristics to guide treatment but applications of multi-omic approaches to sub-phenotyping in these areas are sparse. The next iteration of the PH clinical classification is likely to reflect several emerging PH phenotypes and improve the next generation of prognostication tools, clinical trial design, and improve treatment selection in clinical practice.

Left atrial acceleration factor as a magnetic resonance 4D flow measure of mean pulmonary artery wedge pressure in pulmonary hypertension.

BackgroundMean pulmonary artery wedge pressure (PAWP) represents a right heart catheter (RHC) surrogate measure for mean left atrial (LA) pressure and is crucial for the clinical classification of pulmonary hypertension (PH). Hypothesizing that PAWP is related to acceleration of blood throughout the LA, we investigated whether an adequately introduced LA acceleration factor derived from magnetic resonance (MR) four-dimensional (4D) flow imaging could provide an estimate of PAWP in patients with known or suspected PH.MethodsLA 4D flow data of 62 patients with known or suspected PH who underwent RHC and near-term 1.5 T cardiac MR (ClinicalTrials.gov identifier: NCT00575692) were retrospectively analyzed. Early diastolic LA peak outflow velocity (vE) as well as systolic (vS) and early diastolic (vD) LA peak inflow velocities were determined with prototype software to calculate the LA acceleration factor (α) defined as α = vE/[(vS + vD)/2]. Correlation, regression and Bland-Altman analysis were employed to investigate the relationship between α and PAWP, α-based diagnosis of elevated PAWP (>15 mmHg) was analyzed by receiver operating characteristic curve analysis.Resultsα correlated very strongly with PAWP (r = 0.94). Standard deviation of differences between RHC-derived PAWP and PAWP estimated from linear regression model (α = 0.61 + 0.10·PAWP) was 2.0 mmHg. Employing the linear-regression-derived cut-off α = 2.10, the α-based diagnosis of elevated PAWP revealed the area under the curve 0.97 with sensitivity/specificity 93%/92%.ConclusionsThe very close relationship between the LA acceleration factor α and RHC-derived PAWP suggests α as potential non-invasive parameter for the estimation of PAWP and the distinction between pre- and post-capillary PH.

TO DRAIN OR NOT TO DRAIN: A THERAPEUTIC CONUNDRUM IN A PATIENT WITH PERICARDIAL TAMPONADE AND EISENMENGER SYNDROME

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: PAH is diagnosed when mean pulmonary artery pressure is greater or equal to 20 mmHg at rest with a pulmonary vascular resistance =3 Wood units. In regions without endemic schistosomiasis, it is commonly idiopathic (1). Eisenmenger syndrome (ES) is the most advanced form of pulmonary arterial hypertension (PAH) and is associated with several congenital heart defects such as ASDS, VSDS etc. CASE PRESENTATION: We present the case of a 30-year-old patient with a past medical history of Trisomy-21, unrestricted ventricular septal defect (VSD) complicated by Eisenmenger Syndrome, PAH (On Treprostinil and Bosentan), chronic hypoxia and Hashimoto's Thyroiditis, who presented from his group home for acute on chronic shortness of breath and fever. Initially, he was hypoxic and hypotensive with signs of severe volume overload on physical exam. Oxygen saturations improved mildly on high flow nasal cannula (HFNC). CT chest and bedside echocardiogram showed a massive pericardial effusion (4.5 cm at the largest point) with tamponade physiology, and pulsus paradoxus (Figure 1,2,3). He was started on vasopressors, inotropes, intravenous prostacyclin and inhaled epoprostenol. Extracorporeal membrane oxygen (ECMO) was planned to stabilize him and drain the effusion, but the family refused ECMO. A Swanz Ganz catheter was placed under fluoroscopic guidance to help guide management but it crossed the VSD and inadvertently ended up in the aorta after which it was removed. After multiple discussions with adult congenital heart disease experts, it was decided that draining the pericardial effusion was not an option given the concern for acute right ventricular failure which could precipitate hemodynamic collapse and cardiac arrest. Another concern was bleeding complications especially bleeding into the pericardial cavity from inadvertently puncturing the multiple collateral vessels that such patients develop. The patient gradually developed increasing vasopressor requirements and eventually passed away. DISCUSSION: A pericardial effusion develops when fluid accumulates between the two layers of pericardium. In PAH, it may develop due to elevated right atrial pressures or underlying connective tissue disease. Its presence in PAH is associated with a significantly increased risk of death and the decision to drain such an effusion remains highly controversial. Multiple studies have reported dismal prognosis of patients who have had such effusions drained (2). The Euro heart survey reported that mortality was particularly high in patients with Eisenmenger's, and they had an increased frequency of major bleeding events as well (2). CONCLUSIONS: Pericardial effusion drainage in patients with pulmonary arterial hypertension is controversial and is associated with poor outcomes. Mortality is particularly high in patients with Eisenmenger's, and a multidisciplinary approach should be utilized to manage such patients. REFERENCE #1: Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913. REFERENCE #2: Engelfriet PM, Duffels MG, Möller T, et al. Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart. 2007;93(6):682-687. DISCLOSURES: No relevant relationships by Saad Farooq, source=Web Response No relevant relationships by ELLIOT SULTANIK, source=Web Response No relevant relationships by Guy Weigold, source=Web Response No relevant relationships by Omar Yacob, source=Web Response

English

In this review, we have discussed pulmonary hypertension including definition, classification, pathophysiology, epidemiology, diagnosis and treatment of each class of PH as per latest available data and guidelines. Pulmonary hypertension is defined as an increase in mean pulmonary arterial pressure of ≥ 20 mmHg at rest. The clinical classification of pulmonary hypertension (as per world health organization) includes five different classes constructed on the basis of clinical causes of pulmonary hypertension. The main pathophysiology involved in the development of pulmonary hypertension of all types is prolonged pulmonary vasoconstriction caused by multiple factors which ultimately leads to pulmonary vascular remodelling (structural as well as functional). The primary treatment of pulmonary hypertension comprises of correction/control of underlying cause of pulmonary hypertension. The prevalence of pulmonary hypertension is increasing in developed as well as developing countries and thus its awareness is important for timely diagnosis and management of this chronic condition. The main aim of our review is to provide all the necessary information regarding pulmonary hypertension in one document. KEYWORDS Pulmonary Hypertension, Chronic Thromboembolism, Left Heart Disease, Lung Disease, Pulmonary Arterial Hypertension

PULMONARY HYPERTENSION STILL AN ‘ORPHAN LUNG DISEASE’ IN PAKISTAN

In our country when it comes to diagnosis and treatment of Pulmonary Hypertension (PH) especially Pulmonary Arterial Hypertension (PAH), it seems that it is still an Orphan Lung disease. Whether it is data about its prevalence in our country, available diagnostic services or treatment options, one may easily feel the scarcity in all mentioned areas.
 Most current classification of PH, categorizes it into 5 groups.1 However this categorization requires availability of diagnostic tools especially right heart catheterization data to classify and know the severity of PH and to offer targeted treatment to patients who belong to group 1 PH i.e. Pulmonary Arterial Hypertension (PAH).
 Studies done about PH prevalence in Pakistan have mainly focused on data in selected patients group e.g. in patients with Chronic Obstructive Pulmonary Diseases (COPD) or Systemic Lupus Erythematosus (SLE).2,3 All of these studies relied on diagnosis without using the diagnostic bench mark i.e. Right heart catheterization. Moreover, effects of targeted treatment for PAH have also been studied only in selected group of patients e.g. COPD.4,5
 While above work by the learned colleagues has to be appreciated, it emphasizes the need to,
 
 Spread the awareness about PH more so to reduce inadvertent use of targeted treatment which may prove detrimental outside group 1 PH and should only be considered at specialized centers.
 Develop specialized centers with required diagnostic services especially Lung functional and anatomical evaluation and Right heart catheterization.
 Establish PH registries (at least one in each province) which can play a vital role to collect data and ensure effective evidence based patient management.
 
 This may be an uphill task however the right direction to move forward.
 
 REFERENCES
 
 Simonneau G, Montani D, David SC, Christopher PD, Michael AG, Michael K, at el. Paul G. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913.
 Amir S, Azmat A, Raza U, Hamid N, Zafar I, Shahida N, at el. Frequency of Pulmonary Hypertension in COPD patients. Pak J Chest Med. 2017;23(4):144-50.
 Sadia A, Aflak R, Tafazzul H, Ahmed A. Frequency and predictors of Pulmonary Hypertension in patients with SLE. Pak J Med Sci. 2019;35(1):86-9.
 Nasir H, Faisal F, Kausar R, Saadia A, Anjum N, Shafi K, at el. Efficacy of bosentan in the treatment of pulmonary hypertension; a prospective study focusing on safety and efficacy in patients with COPD. J Lung Pulm Respir Res. 2018;5(2):67-72.
 Sharieff S. Effect of sildenafil in primary pulmonary hypertension. Pak J Med Sci. 2007;23(2):264.

Pulmonary hypertension thresholds: time to lower further?

Since the first World Symposium on Pulmonary Hypertension in 1973, pulmonary hypertension has been arbitrarily defined as mean pulmonary arterial pressure (PAP) of at least 25 mm Hg at rest. This conservative threshold minimised the risk of overdiagnosis and overtreatment of pulmonary hypertension. However, evidence has since shown that the mean PAP in the general population is 14·0 mm Hg (SD 3·3), 1 Kovacs G Berghold A Scheidl S et al. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009; 34: 888-894 Crossref PubMed Scopus (624) Google Scholar suggesting that 20 mm Hg should be considered as above the upper limit of normal (ie, above the 97·5th percentile). This finding led to a newer, evidence-based, haemodynamic definition of pulmonary hypertension as a mean PAP of more than 20 mm Hg. 2 Simonneau G Montani D Celermajer DS et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019; 531801913 Crossref PubMed Scopus (1114) Google Scholar Precapillary pulmonary hypertension, generally seen in patients with pulmonary arterial hypertension, pulmonary hypertension due to chronic lung diseases or chronic thromboembolism, and a subset of patients with pulmonary hypertension due to left heart disease, was also characterised by the concomitant presence of pulmonary artery wedge pressure of 15mm Hg or less and pulmonary vascular resistance (PVR) of 3 Wood units or more. 2 Simonneau G Montani D Celermajer DS et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019; 531801913 Crossref PubMed Scopus (1114) Google Scholar The PVR threshold was already recognised as conservative and somewhat arbitrary, because preliminary data suggested the upper limit of normal for PVR could be around 2 Wood units. 1 Kovacs G Berghold A Scheidl S et al. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009; 34: 888-894 Crossref PubMed Scopus (624) Google Scholar Pulmonary vascular resistance and clinical outcomes in patients with pulmonary hypertension: a retrospective cohort studyThese data widen the continuum of clinical risk for mortality and heart failure in patients referred for RHC with elevated pulmonary artery pressure to include PVR of around 2.2 Wood units and higher. Testing the generalisability of these findings in at-risk populations with fewer cardiopulmonary comorbidities is warranted. Full-Text PDF

Haemodynamic definitions and updated clinical classification of pulmonary hypertension.

Since the 1st World Symposium on Pulmonary Hypertension (WSPH) in 1973, pulmonary hypertension (PH) has been arbitrarily defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest, measured by right heart catheterisation. Recent data from normal subjects has shown that normal mPAP was 14.0±3.3 mmHg. Two standard deviations above this mean value would suggest mPAP >20 mmHg as above the upper limit of normal (above the 97.5th percentile). This definition is no longer arbitrary, but based on a scientific approach. However, this abnormal elevation of mPAP is not sufficient to define pulmonary vascular disease as it can be due to an increase in cardiac output or pulmonary arterial wedge pressure. Thus, this 6th WSPH Task Force proposes to include pulmonary vascular resistance ≥3 Wood Units in the definition of all forms of pre-capillary PH associated with mPAP >20 mmHg. Prospective trials are required to determine whether this PH population might benefit from specific management.Regarding clinical classification, the main Task Force changes were the inclusion in group 1 of a subgroup “pulmonary arterial hypertension (PAH) long-term responders to calcium channel blockers”, due to the specific prognostic and management of these patients, and a subgroup “PAH with overt features of venous/capillaries (pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis) involvement”, due to evidence suggesting a continuum between arterial, capillary and vein involvement in PAH.

Approach to Pulmonary Hypertension: From CT to Clinical Diagnosis.

Pulmonary hypertension (PH) is a condition characterized by increased pressure in the pulmonary circulation. It may be idiopathic or arise in the setting of other clinical conditions. Patients with PH tend to present with nonspecific cardiovascular or respiratory symptoms. The clinical classification of PH was recently revised at the World Health Organization symposium in Nice, France, in 2013. That consensus statement provided an updated classification based on the shared hemodynamic characteristics and management of the different categories of PH. Some features seen at computed tomography (CT) can suggest a subtype or probable cause of PH that may facilitate placing the patient in the correct category. These features include findings in the pulmonary arteries (peripheral calcification, peripheral dilatation, eccentric filling defects, intra-arterial soft tissue), lung parenchyma (centrilobular nodules, mosaic attenuation, interlobular septal thickening, bronchiectasis, subpleural peripheral opacities, ground-glass opacities, diffuse nodules), heart (congenital lesions, left heart disease, valvular disease), and mediastinum (hypertrophied bronchial arteries). An approach based on identification of these CT features in patients with PH will allow the radiologist to play an important role in diagnosis and help guide the clinician in management of PH. ©RSNA, 2018.

Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are categorized as Group 1' in the clinical classification of pulmonary hypertension. No medical therapy has been proven to be effective in patients with PVOD/PCH. Imatinib is a molecular targeted drug and was expected to be effective in patients with pulmonary arterial hypertension. We evaluated its efficacy and safety in patients with PVOD/PCH. In the present observational study, 9 patients with PVOD/PCH received imatinib. Clinical data including exercise capacity and hemodynamics at baseline and at follow-up were compared. Survival rate of patients treated with imatinib was compared to those of 7 patients who did not treated with imatinib. Imatinib was prescribed at doses of 100-400mg/day and was well-tolerated. At follow-up, World Health Organization functional class and brain natriuretic peptide levels significantly improved. Mean pulmonary arterial pressure was significantly reduced (from 56.8±8.3 to 43.7±9.0mmHg) with preserved cardiac index. Patients were treated with imatinib for 797.2±487.0 days. Seven patients (77.8%) died and 2 patients (22.2%) underwent lung transplantation. Mean survival time in patients treated with imatinib therapy was 1493.7±196.3 days (95% confidence interval, 1108.9-1878.5 days), significantly longer than those without imatinib treatment (713.0±258.1 days, log-rank test, P=0.04). Imatinib improved exercise capacity, hemodynamics and survival in patients with PVOD/PCH. In patients with PVOD/PCH, who have no effective medical therapy available, imatinib might function as a bridge to lung transplantation, and may become a potential therapeutic option to improve their survival.

Invasive haemodynamic evaluation of the pulmonary circulation in pulmonary hypertension.

The term pulmonary hypertension refers to a serious condition characterised by high pulmonary vascular pressure, mainly as a consequence of various cardiac and respiratory diseases. Current clinical classification of pulmonary hypertension considers five distinct groups. Transthoracic echocardiography represents the first and most important noninvasive screening tool for estimating the probability of pulmonary hypertension. The diagnostic approach to pulmonary hypertension is supported by a proposed algorithm, which identifies the underlying cause. The definitive diagnosis and classification of pulmonary hypertension requires invasive confirmation of an elevated pulmonary artery mean pressure during a right heart catheterisation at rest. Pulmonary artery wedge pressure assessment has a pivotal role in differentiating precapillary from postcapillary pulmonary hypertension. The correct acquisition and interpretation of invasive pulmonary haemodynamic variables play a central role, not only in confirming the diagnosis but also in prognostication and treatment decision-making. During right heart catheterisation correct zero levelling of the external pressure transducer and pressure tracing readings at end-expiration should be assured. Obese patients and patients with obstructive lung diseases require special attention, given that spontaneous positive end-expiratory intrathoracic pressures are frequently observed. Because pressure and flow determinations with a fluid-filled flow-directed thermodilution catheter are potentially insufficiently precise, it is recommended to average at least three measurements. Acute vasoreactivity testing is indicated only in selected patients. Recent data suggest that invasive pulmonary haemodynamic measurement during exercise may be more sensitive than resting haemodynamics for early diagnosis, for treatment response assessment and for prognostic purposes.

Pulmonary Veno-Occlusive Disease in a Patient with History of Major Depressive Disorder

Introduction: Pulmonary veno-occlusive disease (PVOD) represents a specific subgroup of the group 1 of the clinical classification of pulmonary hypertension. Case presentation: We introduce a young male patient with history of major depressive disorder who was on psychiatric medications and presented with gradually progressive dyspnea and syncope. The preliminary diagnostic tools showed the presence of pulmonary hypertension; further imaging studies and right heart catheterization showed findings consistent with PVOD. Conclusion: To best of our knowledge, this is the first report of PVOD in a patient taking psychiatric medications.

Hypertension pulmonaire : définition, classification et traitements

Pulmonary hypertension (PH) is a cardio-pulmonary disorder that may involve multiple clinical conditions and can complicate the majority of cardiovascular and respiratory diseases. Its definition is an increase in mean pulmonary artery pressure (mPAP) \hbox{$\geqslant $} ⩾ 25 mmHg at rest, leading to right heart failure and ultimately death. The clinical classification of pulmonary hypertension (PH) categorizes PH into groups which share similar pathophysiological and hemodynamic characteristics and treatments. Five groups of disorders that cause PH are identified: pulmonary arterial hypertension (Group 1) which is a pre-capillary PH, defined by a normal pulmonary artery wedge pressure (PAWP) \hbox{$\leqslant $} ⩽ 15 mmH, due to remodelling of the small pulmonary arteries (<500 μm); pulmonary hypertension due to left heart disease (Group 2) which is a post-capillary PH, defined by an increased pulmonary artery wedge pressure (PAWP) >15 mmHg; pulmonary hypertension due to chronic lung disease and/or hypoxia (Group 3); chronic thrombo-embolic pulmonary hypertension (Group 4); and pulmonary hypertension due to unclear and/or multifactorial mechanisms (Group 5). PAH (PH group 1) can be treated with agents targeting three dysfunctional endothelial pathways of PAH: nitric oxide (NO) pathway, endothelin-1 pathway and prostacyclin pathway. Patients at low or intermediate risk can be treated with either initial monotherapy or initial oral combination therapy. In patients at high risk initial combination therapy including intravenous prostacyclin analogues should be considered. Patients with inadequate clinical response to maximum treatment (triple therapy with an intravenous prostacyclin) should be assessed for lung transplantation. Despite progresses, PAH remains a fatal disease with a 3-year survival rate of 58%. Treatment of group 2, group 3 and group 5 PH is the treatment of the causal disease and PAH therapeutics are not recommended. Treatment of group 4 PH is pulmonary endarteriectomy if patients are eligible, otherwise balloon pulmonary angioplasty and/or medical therapy can be considered.

Magnetic Resonance Imaging for Pulmonary Hypertension

Pulmonary hypertension (PH) is a potentially life-threatening disease. Clinical classification of PH has undergone multiple modifications and was last updated in 2008. Initial detection and classification rely on a combination of invasive and noninvasive tests, among which the most important are echocardiography, right-sided heart catheterization, and computed tomography. Treatment response assessment and monitoring are focused on the functional evaluation of the right ventricle, and magnetic resonance imaging is the noninvasive test of choice as its accuracy and reproducibility are superior to echocardiography. In this article, we discuss our PH evaluation magnetic resonance imaging protocol, which has been customized to provide clinicians with the information needed to assess right-sided heart functional status and determine response to treatment or disease progression.

Classification of Pulmonary Hypertension

Classification of pulmonary hypertension groups patients with similar pathological findings, hemodynamic profiles, and management strategies. Minor modifications have been made to the current classification system, particularly within Group 1 pulmonary arterial hypertension. This article summarizes the published conclusions of the Fifth World Symposium of Pulmonary Hypertension task force that addressed the updated clinical classification of pulmonary hypertension.

Insulin resistance in pulmonary arterial hypertension, is it a novel disease modifier?

Background:Recent studies have introduced glucose intolerance and insulin resistance (IR) as novel risk factors in patients with pulmonary arterial hypertension (PAH).Objectives:We aimed to investigate the prevalence of glucose intolerance and IR in patients with PAH and their correlation with functional capacity and prognostic factors.Patients and Methods:Sixty-nine patients with pulmonary arterial hypertension (class I Pulmonary hypertension in accordance with updated clinical classification of pulmonary hypertension) scheduled for right heart catheterization were enrolled. FBS, HbA1c, lipid profile, pro –BNP and hs-CRP were measured along with a 6-minute walk test (6-MWT) and obtaining demographic, functional and hemodynamic data. Fasting triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) was used as a surrogate of insulin sensitivity. Using published criteria, HbA1c ≤ 5.9% defined as normal, 6.0-6.4% as glucose intolerance, and ≥ 6.5% as diabetes. All patients were followed for a year regarding development of any cardiovascular event (mortality and/or hospitalization).Results:In total, 76.8% of patients were female: 61% of them had idiopathic PAH, 33% Eisenmenger syndrome, and 6% PAH secondary to a connective tissue disease. With respect to TG/HDL-C, 43.5% of patients had IR and 47.8% of patients had HbA1c > 6. There was no difference between IR and insulin sensitive (IS) group or glucose intolerance and sensitive group regarding NYHA class, 6MWT, Pro BNP, hs-CRP and hemodynamic data and there was no correlation between IR or glucose intolerance and any event.Conclusions:Unrecognized glucose intolerance and IR are common in PAH. However, further studies are needed to show whether glucose or insulin dysregulation plays any role in PAH pathogenesis or it is secondary to advanced PAH.

Transforming Growth Factor-β Signaling in Schistosomiasis-Induced Pulmonary Hypertension

Schistosomiasis is a parasitic disease affecting a large portion of the global human population and represents one of the most common causes of pulmonary hypertension (PH) around the world.1–3 Schistosomiasis-associated pulmonary arterial hypertension (PAH) is classified in the group 1.4.5, according to the current clinical classification of pulmonary hypertension from Dana Point in 2008.4 It has been suggested that pulmonary vascular remodeling in response to Schistosoma infection is similar to other forms of PAH, such as idiopathic PAH.2 In addition, the presence of prominent granulomatous inflammation and fibrosis has been described.1,5,6 In recent years, we have noticed that augmented inflammation is indeed an unavoidable player in the pathology of idiopathic PAH, and the literature …

Effects of treatment with a combination of cardiac rehabilitation and bosentan in patients with pulmonary Langerhans cell histiocytosis associated with pulmonary hypertension

Pulmonary hypertension (PH), which is classified as group 5 in the clinical classification of PH, is sometimes a complication of Pulmonary langerhans cell histiocytosis (PLCH), and is associated with high mortality. A 36-year-old woman had suffered from severe dyspnea 9 years previously and was diagnosed with PLCH and was on a waiting list for a lung transplant. Right heart failure had been observed and the mean pulmonary artery pressure was over 40 mmHg. The patient was diagnosed as PLCH with PH. After combined treatment with exercise rehabilitation and bosentan for 6 months, the cardiothoracic ratio, brain natriuretic peptide, and bodyweight were significantly decreased (cardiothoracic ratio from 43 to 38%, brain natriuretic peptide from 284 to10 pg/ml and bodyweight from 63 to 58 kg). Six-minute walk test also improved from 214 to 275 meters and the SF36 score for screening of depressive and anxiety disorders was improved. This is the report demonstrating the efficacy and safety of cardiac rehabilitation in combination with bosentan in a single patient with PLCH associated with PH.

A decade of achievement in pulmonary hypertension

The past decade has witnessed unprecedented change in the field of pulmonary hypertension (PH). PH has previously been called an orphan disease; that is, a condition that affects few individuals and is overlooked by the medical profession and pharmaceutical companies [1]. Although undoubtedly rare, the concept that PH is “overlooked” cannot be considered to be the case today. In recent years there have been a number of important publications in the field that have significantly improved our understanding of PH, helped guide patient management and laid foundations for future research [2]. The articles in this issue of the European Respiratory Review aim to discuss such contemporary issues in PH. The authors, all experts in the field of PH, delivered the presentations upon which the papers are based at two international meetings sponsored by Actelion Pharmaceuticals (Allschwil, Switzerland). These meetings – the Fourth International Systemic Sclerosis Forum, Barcelona, Spain, February 5–6, 2011 and the Tenth International Pulmonary Hypertension Forum, Munich, Germany, March 26–27, 2011 – were each attended by over 1,000 healthcare professionals from all over the world, thus emphasising the increasing global interest in this devastating disease. The clinical classification of PH has evolved since the initial proposal at the first international conference on primary PH in 1973 [3]. Two updates, one from the Second and Third World Symposia on Pulmonary Hypertension in Evian, France, 1998 and Venice, Italy, 2004 [4], and the other from the Fourth World Symposium on Pulmonary Hypertension in Dana Point, CA, USA, 2008 [5] have been published in the past 10 yrs. The more recent set of guidelines, based on the proceedings from Dana Point [5, 6], have been jointly published by the European Society of Cardiology (ESC) and European Respiratory Society …

Prevalence of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the United States

Background:The prevalence of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in the US is largely unknown. Prior research has estimated PAH prevalence in Europe at ∼15–52 per million.Methods:Using a privately insured claims database (1999–2007) for the under age 65 population and a Medicare claims database for the 65+ population, and following the current clinical classification of PH, CTEPH patients were identified as having: ≥2 claims for pulmonary hypertension (PH) [ICD-9-CM: 416.0, 416.8]; ≥1 claim for pulmonary embolism (PE) ≤12 months prior or 1 month after the initial PH claim (index date). PAH patients were identified: ≥2 claims for primary PH [416.0]; no left heart disease, lung diseases, CTEPH, or miscellaneous PH diagnoses ≤12 months prior or 1 month after the index date. Both cohorts were required to have ≥1 claim for right heart catheterization ≤6 months prior to any PH claim, or ≥1 claim for echocardiogram ≤6 months prior to a specialist-diagnosed PH claim. Age- and gender-standardized prevalence rates per million individuals (PMI) were calculated using appropriate population weights.Results:Prevalence rates (95% CI) of CTEPH were estimated at 63 (34–91) PMI among the privately insured (<65), and 1007 (904–1111) PMI among the Medicare population (≥65). The corresponding estimates for PAH were 109 (71–146) PMI among the <65 population, and 451 (384–519) PMI for Medicare.Limitations:Identification of PAH and CTEPH patients in administrative claims data is challenging, due to lack of specific ICD-9-CM codes for the conditions and risk of misdiagnosis.Conclusions:Prevalence rates of CTEPH and PAH increase with age, and are higher among women. The increased risk of PE may explain the sharp age gradient for CTEPH prevalence. The estimated US prevalence of PAH is higher than existing estimates.

Cell-based therapies in pulmonary hypertension: who, what, and when?

pulmonary hypertension (PH), diagnosed when mean pulmonary arterial pressure exceeds the upper limits of normal (i.e., >25 mmHg) at rest (2), occurs in a variety of clinical situations and is associated with a broad spectrum of histological patterns and abnormalities. PH is currently classified into five distinct World Health Organization (WHO) groups, based on common clinical parameters, potential etiological mechanisms, and responses to treatment (22). Although any form of PH can contribute to increased patient morbidity and mortality, pulmonary arterial hypertension (PAH) (WHO group 1) is a particularly severe and progressive form associated with right heart failure and premature death (1). At present, therapeutic approaches to stabilize or reverse this debilitating condition involve treatment with one or a combination of up to three specific classes of agents, including prostacyclin analogs, endothelin-1 receptor antagonists, and/or phosphodiesterase-5 inhibitors. Retrospective (meta)analyses of these therapeutic strategies have demonstrated a reduction in mortality with their use (7, 12); however, many experts believe that current PAH treatment is inadequate given the persistently high mortality rate and functional hemodynamic impairment in many patients. These observations have led to continued intensive investigation into pathogenetic mechanisms and many proposals for additional alternative new therapies (20, 24). Among the potential new therapies, increasing interest in the role of endothelial progenitor cells (EPCs) as a cell-based therapy has emerged. However, issues remain regarding what group of PH patients are most likely to benefit from treatment, at what point in the disease is treatment most likely to be successful, and what types of cells should be utilized for therapy.