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Zicans M, Kazoka D, Pilmane M, Skride A. The Importance of Topographical Recognition of Pulmonary Arteries in Diagnostics and Treatment of CTEPH, Based on an Analysis of a Dissected Case Model-A Pilot Study. Diagnostics (Basel) 2024; 14:1684. [PMID: 39125560 PMCID: PMC11311259 DOI: 10.3390/diagnostics14151684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/25/2024] [Accepted: 08/01/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND Knowledge of the anatomy of pulmonary arteries is essential in many invasive procedures concerning pulmonary circulation. In the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH), two-dimensional (2D) pulmonary angiography is used. Recognizing the topographic course of the pulmonary arteries and understanding the status in three dimensions (3D) is paramount. This study aimed to evaluate and describe the branching variant of pulmonary arteries in a single case, as well as morphological parameters of the segmental arteries, like length, diameter and branching angles. METHODS One pair of embalmed human cadaver lungs was dissected by a scalpel and surgical forceps and was measured up to the subsegmental arteries. RESULTS The diameters (ranging from 3.04 to 9.29 mm) and lengths (ranging from 9.09 to 53.91 mm) of the pulmonary segmental arteries varied. The proximal branching angles were wide and close to perpendicular, while distally, the angles between the segmental and subsegmental arteries were narrower (30-45°). Upon evaluating the branching, rare variations were identified and delineated, notably in the lower lobes of both lungs. CONCLUSIONS Utilizing knowledge and data in clinical settings is instrumental for effectively diagnosing and treating CTEPH. Further research is required to explore the complications in invasive procedures related to various anatomical variations.
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Affiliation(s)
- Matiss Zicans
- Faculty of Medicine, Rīga Stradiņš University, LV-1007 Riga, Latvia
| | - Dzintra Kazoka
- Institute of Anatomy and Anthropology, Rīga Stradiņš University, LV-1010 Riga, Latvia; (D.K.); (M.P.)
| | - Mara Pilmane
- Institute of Anatomy and Anthropology, Rīga Stradiņš University, LV-1010 Riga, Latvia; (D.K.); (M.P.)
| | - Andris Skride
- Department of Internal Diseases, Rīga Stradiņš University, LV-1007 Riga, Latvia;
- Pauls Stradiņš Clinical University Hospital, LV-1002 Riga, Latvia
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Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jaïs X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. THE LANCET. RESPIRATORY MEDICINE 2024; 12:e21-e30. [PMID: 38548406 DOI: 10.1016/s2213-2600(24)00027-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2024]
Abstract
BACKGROUND Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. FINDINGS Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 71·5% of baseline in the macitentan group and to 87·6% in the placebo group (geometric means ratio 0·81, 95% CI 0·70-0·95, p=0·0098). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). INTERPRETATION In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. FUNDING Actelion Pharmaceuticals Ltd.
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Affiliation(s)
- Hossein-Ardeschir Ghofrani
- German Center for Lung Research (DZL), Giessen, Germany; University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; Department of Medicine, Imperial College London, London, UK.
| | - Gérald Simonneau
- Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France; INSERM U-999, Le Kremlin-Bicêtre, France
| | - Andrea M D'Armini
- Department of Cardio-Thoracic and Vascular Surgery, Heart and Lung Transplantation and Pulmonary Hypertension Unit, Foundation IRCCS Policlinico San Matteo, University of Pavia School of Medicine, Pavia, Italy
| | - Peter Fedullo
- Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, CA, USA
| | - Luke S Howard
- National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK; National Heart & Lung Institute, Imperial College London, London, UK
| | - Xavier Jaïs
- Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France; INSERM U-999, Le Kremlin-Bicêtre, France
| | - David P Jenkins
- Department of Cardiothoracic Surgery, Papworth Hospital, Cambridge, UK
| | - Zhi-Cheng Jing
- State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Michael M Madani
- Division of Cardiovascular and Thoracic Surgery, University of California San Diego Medical Center, San Diego, CA, USA
| | | | - Eckhard Mayer
- Department of Thoracic Surgery, Kerckhoff-Clinic, Bad Nauheim, Germany
| | | | | | - Nick H Kim
- Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, CA, USA
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3
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Zhan S, Wang L, Wang W, Li R. Analysis of genes characterizing chronic thrombosis and associated pathways in chronic thromboembolic pulmonary hypertension. PLoS One 2024; 19:e0299912. [PMID: 38451963 PMCID: PMC10919650 DOI: 10.1371/journal.pone.0299912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/17/2024] [Indexed: 03/09/2024] Open
Abstract
PURPOSE In chronic thromboembolic pulmonary hypertension (CTEPH), fibrosis of thrombi in the lumen of blood vessels and obstruction of blood vessels are important factors in the progression of the disease. Therefore, it is important to explore the key genes that lead to chronic thrombosis in order to understand the development of CTEPH, and at the same time, it is beneficial to provide new directions for early identification, disease prevention, clinical diagnosis and treatment, and development of novel therapeutic agents. METHODS The GSE130391 dataset was downloaded from the Gene Expression Omnibus (GEO) public database, which includes the full gene expression profiles of patients with CTEPH and Idiopathic Pulmonary Arterial Hypertension (IPAH). Differentially Expressed Genes (DEGs) of CTEPH and IPAH were screened, and then Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analyses were performed on the DEGs; Weighted Gene Co-Expression Network Analysis (WGCNA) to screen the key gene modules and take the intersection genes of DEGs and the key module genes in WGCNA; STRING database was used to construct the protein-protein interaction (PPI) network; and cytoHubba analysis was performed to identify the hub genes. RESULTS A total of 924 DEGs were screened, and the MEturquoise module with the strongest correlation was selected to take the intersection with DEGs A total of 757 intersecting genes were screened. The top ten hub genes were analyzed by cytoHubba: IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4. CONCLUSION IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4 have diagnostic and therapeutic value in CTEPH disease, especially playing a role in chronic thrombosis. The discovery of NF-κB, AP-1 transcription factors, and TNF signaling pathway through pivotal genes may be involved in the disease progression process.
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Affiliation(s)
| | - Liu Wang
- Xuzhou Central Hospital, Xuzhou, China
| | | | - Ruoran Li
- Bengbu Medical College, Bengbu, China
- Xuzhou Central Hospital, Xuzhou, China
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Öngen HG, Akdeniz B, Düzenli MA, Chernyavsky A, Dabar G, Idrees M, Khludeeva E, Kültürsay H, Lukianchikova V, Martynyuk T, Moğulkoç N, Mukarov MA, Mutlu B, Okumuş G, Omarov A, Önen ZP, Sakkijha H, Shostak N, Simakova M, Tokgözoğlu L, Tomskaya T, Yildirim H, Zateyshchikov D, Hechenbichler K, Kessner S, Schauerte I, Turgut N, Vogtländer K, Aldalaan A. Diagnosis and Treatment Patterns of Chronic Thromboembolic Pulmonary Hypertension in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia: A Registry Study. Drugs Real World Outcomes 2024; 11:149-165. [PMID: 38381283 DOI: 10.1007/s40801-023-00407-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2023] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. OBJECTIVE This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. METHODS A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3 years' observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. RESULTS The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142 patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. CONCLUSIONS These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. CLINICALTRIALS gov: NCT02637050; registered December 2015.
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Affiliation(s)
- Hürrem Gül Öngen
- Cerrahpasa Faculty of Medicine, Istanbul University, 34098, Istanbul, Turkey.
| | - Bahri Akdeniz
- Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey
| | | | - Alexander Chernyavsky
- E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
| | | | - Majdy Idrees
- Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Elena Khludeeva
- State Budgetary Healthcare Institution, Primorskaya Regional Clinical Hospital No. 1, Vladivostok, Russia
| | | | - Vera Lukianchikova
- Regional State Budgetary Healthcare Institution, Regional Clinical Hospital No. 1, Khabarovsk, Russia
| | - Tamila Martynyuk
- Federal State Budget Institution, National Medical Center of Cardiology, Moscow, Russia
| | | | - Murat A Mukarov
- National Research Cardiac Surgery Center, Astana, Kazakhstan
| | - Bülent Mutlu
- Faculty of Medicine, Marmara University, Istanbul, Turkey
| | - Gülfer Okumuş
- Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Anuar Omarov
- Institute of Cardiology in Almaty, Almaty, Kazakhstan
| | | | | | - Nadezhda Shostak
- State Budgetary Healthcare Institution, Pirogov City Clinical Hospital No. 1 of Moscow City, Moscow, Russia
| | - Maria Simakova
- Federal State Budgetary Institution, Almazov National Medical Research Center, Saint Petersburg, Russia
| | | | - Tatyana Tomskaya
- State Budgetary Institution of the Republic of Sakha (Yakutia), Republican Hospital No. 1, Yakutsk, Russia
| | | | - Dmitry Zateyshchikov
- State Budgetary Healthcare Institution, City Clinical Hospital No. 51 of Moscow Health Department, Moscow, Russia
| | | | | | | | | | | | - Abdullah Aldalaan
- Department of Pulmonary Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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Tsuchiya N, Xu YY, Ito J, Yamashiro T, Ikemiyagi H, Mummy D, Schiebler ML, Yonemoto K, Murayama S, Nishie A. Chronic thromboembolic pulmonary hypertension is associated with a loss of total lung volume on computed tomography. World J Radiol 2023; 15:146-156. [PMID: 37275304 PMCID: PMC10236971 DOI: 10.4329/wjr.v15.i5.146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 04/04/2023] [Accepted: 04/24/2023] [Indexed: 05/23/2023] Open
Abstract
BACKGROUND Although lung volumes are usually normal in individuals with chronic thromboembolic pulmonary hypertension (CTEPH), approximately 20%-29% of patients exhibit a restrictive pattern on pulmonary function testing.
AIM To quantify longitudinal changes in lung volume and cardiac cross-sectional area (CSA) in patients with CTEPH.
METHODS In a retrospective cohort study of patients seen in our hospital between January 2012 and December 2019, we evaluated 15 patients with CTEPH who had chest computed tomography (CT) performed at baseline and after at least 6 mo of therapy. We matched the CTEPH cohort with 45 control patients by age, sex, and observation period. CT-based lung volumes and maximum cardiac CSAs were measured and compared using the Wilcoxon signed-rank test and the Mann-Whitney u test.
RESULTS Total, right lung, and right lower lobe volumes were significantly reduced in the CTEPH cohort at follow-up vs baseline (total, P = 0.004; right lung, P = 0.003; right lower lobe; P = 0.01). In the CTEPH group, the reduction in lung volume and cardiac CSA was significantly greater than the corresponding changes in the control group (total, P = 0.01; right lung, P = 0.007; right lower lobe, P = 0.01; CSA, P = 0.0002). There was a negative correlation between lung volume change and cardiac CSA change in the control group but not in the CTEPH cohort.
CONCLUSION After at least 6 mo of treatment, CT showed an unexpected loss of total lung volume in patients with CTEPH that may reflect continued parenchymal remodeling.
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Affiliation(s)
- Nanae Tsuchiya
- Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara 903-0125, Okinawa, Japan
| | - Yan-Yan Xu
- Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Junji Ito
- Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara 903-0125, Okinawa, Japan
| | - Tsuneo Yamashiro
- Department of Radiology, Yokohama City University, Yokohama 2360027, Japan
| | - Hidekazu Ikemiyagi
- Department of Cardiovascular Medicine, Nephrology and Neurology, Graduate School of Medicine, University of the Ryukyus, Nishihara 9030125, Okinawa, Japan
| | - David Mummy
- Center for In Vivo Microscopy and Department of Radiology, Duke University, Durham, NC 27710, United States
| | - Mark L Schiebler
- Department of Radiology, University of Wisconsin-Madison, Madison, WI 53792, United States
| | - Koji Yonemoto
- Department of Biostatistics, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Nishihara 903-0215, Okinawa, Japan
| | - Sadayuki Murayama
- Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara 903-0125, Okinawa, Japan
| | - Akihiro Nishie
- Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara 903-0125, Okinawa, Japan
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Butler O, Ju S, Hoernig S, Vogtländer K, Bansilal S, Heresi GA. Assessment for residual disease after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension. ERJ Open Res 2022; 8:00572-2021. [PMID: 35651369 PMCID: PMC9149390 DOI: 10.1183/23120541.00572-2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 03/29/2022] [Indexed: 11/08/2022] Open
Abstract
Objectives Pulmonary endarterectomy (PEA) is recommended for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH) and is potentially curative. However, persistent/recurrent CTEPH post-PEA can occur. Here we describe symptom and diagnostic assessment rates for residual disease post-PEA and longitudinal diagnostic patterns before and after riociguat approval for persistent/recurrent CTEPH after PEA. Methods This US retrospective cohort study analysed MarketScan data (1 January 2002–30 September 2018) from patients who underwent PEA following a CTEPH/pulmonary hypertension (PH) claim with at least 730 days of continuous enrolment post-PEA. Data on pre-specified PH symptoms and the types and timings of diagnostic assessments were collected. Results Of 103 patients (pre-riociguat approval, n=55; post-riociguat approval, n=48), residual PH symptoms >3 months after PEA were reported in 89% of patients. Overall, 89% of patients underwent one or more diagnostic tests (mean 4.6 tests/patient), most commonly echocardiography (84%), with only 5% of patients undergoing right heart catheterisation (RHC). In the post- versus pre-riociguat approval subgroup, assessments were more specific for CTEPH with an approximately two-fold increase in 6-min walk distance and N-terminal prohormone of brain natriuretic protein measurements and ventilation/perfusion scans, and a four-fold increase in RHCs. Conclusions Low RHC rates suggest that many patients with PH symptoms post-PEA are not being referred for full diagnostic workup. Changes to longitudinal diagnostic patterns may indicate increased recognition of persistent/recurrent CTEPH post-PEA; however, there remains a need for greater awareness around the importance of continued follow-up for patients with residual PH symptoms post-PEA. Rates of residual PH symptoms are high after PEA but referral of patients with suspected persistent/recurrent CTEPH following PEA for CTEPH-specific diagnostic assessments is suboptimal, highlighting potential gaps in CTEPH patient care post-PEAhttps://bit.ly/3jfUZlO
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7
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Liu Z, Zhen Y, Lin F, Zheng X, Liu X, Sun G, Ye Z, Wen J, Liu P. Resting heart rate as a preoperative predictor of postoperative atrial fibrillation after pulmonary thromboendarterectomy. J Card Surg 2022; 37:1644-1650. [PMID: 35274764 DOI: 10.1111/jocs.16407] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/13/2022] [Accepted: 02/17/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND As a marker of the autonomic nervous system, resting heart rate is a predictor of postoperative atrial fibrillation (POAF). However, its predictive value for POAF after pulmonary thromboendarterectomy (PTE) has not been adequately studied. METHODS We enrolled 97 patients who underwent PTE in our hospital from December 2016 to November 2021 in this retrospective study. Almost all preoperative characteristics, including electrocardiogram, demographics, hematologic and biochemical indices, echocardiography, and pulmonary hemodynamics, were compared between patients with and without POAF. Multivariate logistic regression analysis was used to identify the independent risk factors for POAF after PTE. RESULTS Overall, 21 patients (21.6%) suffered from POAF after PTE. Compared with patients without POAF, those with POAF were older (p = .049), with a higher resting heart rate (p = .012), and higher platelet count (p = .040). In the binary logistic regression analysis, the resting heart rate (odds ratio [OR] = 1.043, 95% confidence interval [CI] = 1.009-1.078, p = .012) and age (OR = 1.051, 95% CI = 1.003-1.102, p = .037) were independent risk factors for POAF after PTE. The optimal cutoff point of resting heart rate was 89.5 with sensitivity and specificity of 47.6% and 77.6%. When the cutoff value of the age was 54.5, its sensitivity for predicting POAF was 71.4%, with a specificity of 59.2%. CONCLUSIONS POAF is common after PTE surgery, and the incidence may be underestimated. The resting heart rate and age are independent preoperative risk factors for POAF after PTE. Considering the lower predictive power of the resting heart and age, further large-scale studies are needed.
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Affiliation(s)
- Zhan Liu
- Departmen of Cardiovascular Surgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.,Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Yanan Zhen
- Departmen of Cardiovascular Surgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.,Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Fan Lin
- Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Xia Zheng
- Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Xiaopeng Liu
- Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Guang Sun
- Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Zhidong Ye
- Departmen of Cardiovascular Surgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.,Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Jianyan Wen
- Departmen of Cardiovascular Surgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.,Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Peng Liu
- Departmen of Cardiovascular Surgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.,Department of Cardiovascular Surgery, China-Japan Friendship Hospital, Beijing, China
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8
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Julià-Torras J, Almeida Felipe JM, Gándara Del Castillo Á, González-Barboteo J, Forero D, Alegre S, Cuervo-Pinna MÁ, Serna J, Muñoz-Unceta N, Alonso-Babarro A, Miró Catalina Q, Moreno-Alonso D, Porta-Sales J. Prevalence, Clinical Characteristics, and Management of Episodic Dyspnea in Advanced Lung Cancer Outpatients: A Multicenter Nationwide Study-The INSPIRA-DOS Study. J Palliat Med 2022; 25:1197-1207. [PMID: 35196465 DOI: 10.1089/jpm.2021.0562] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background: Episodic dyspnea (ED) is a common problem in patients with advanced lung cancer (LC). However, the prevalence of ED and other related aspects in this patient population is not known. Objectives: To assess and describe the prevalence, clinical features, treatment, and risk factors for ED in outpatients with advanced LC. Design: Multicenter cross-sectional study. Subjects: Consecutive sample of adult outpatients with advanced LC. Measurements: We assessed background dyspnea (BD), the characteristics, triggers, and management of ED. Potential ED risk factors were assessed through multivariate logistic regression. Results: A total of 366 patients were surveyed. Overall, the prevalence of ED was 31.9% (90% in patients reporting BD). Patients reported a median of one episode per day (interquartile range [IQR]: 1-2), with a median intensity of 7/10 (IQR: 5-8.25). ED triggers were identified in 89.9% of patients. ED was significantly associated with chronic obstructive pulmonary disease (p = 0.011), pulmonary vascular disease (p = 0.003), cachexia (p = 0.002), and palliative care (p < 0.001). Continuous oxygen use was associated with higher risk of ED (odds ratio: 9.89; p < 0.001). Opioids were used by 44% patients with ED. Conclusions: ED is highly prevalent and severe in outpatients with advanced LC experiencing BD. The association between intrathoracic comorbidities and oxygen therapy points to alveolar oxygen exchange failure having a potential etiopathogenic role in ED in this population. Further studies are needed to better characterize ED in LC to better inform treatments and trial protocols.
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Affiliation(s)
- Joaquim Julià-Torras
- Palliative Care Department, Institut Català d'Oncologia, Badalona, Spain.,School of Medicine and Health Science, Universitat Internacional de Catalunya, Barcelona, Spain
| | - J M Almeida Felipe
- Palliative Care Unit, Complejo Hospitalario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain
| | | | - Jesús González-Barboteo
- Palliative Care Department, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Spain.,Palliative Care Research Group, EPIBELL Programme, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat (Barcelona), Spain
| | - Diana Forero
- Palliative Care Department, Hospital Universitari Arnau de Vilanova, Lleida, Spain
| | - Salvador Alegre
- Internal Medicine Department, Hospital de San Lázaro, Sevilla, Spain
| | | | - Judit Serna
- Support and Palliative Care Unit, Hospital Universitari Campus Vall d'Hebron, Barcelona, Spain
| | - Nerea Muñoz-Unceta
- Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.,Medical Oncology Department, Hospital Universitario Marqués de Valdecilla and Instituto de Investigación Marqués de Valdecilla (IDIVALL), Santander, Spain
| | | | - Queralt Miró Catalina
- Unitat de Suport a la Recerca de la Catalunya Central, Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina, Sant Fruitós de Bages, Spain.,Servei d'Atenció Primària Bages-Berguedà-Moianès, Gerència Territorial de Barcelona, Institut Català de la Salut, Manresa, Spain
| | - Deborah Moreno-Alonso
- School of Medicine and Health Science, Universitat Internacional de Catalunya, Barcelona, Spain.,Palliative Care Department, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Spain
| | - Josep Porta-Sales
- School of Medicine and Health Science, Universitat Internacional de Catalunya, Barcelona, Spain.,Universitat Internacional de Catalunya, Sant Cugat del Vallès-Barcelona, Spain
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9
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Taweel H, Haddadin I, Heresi G. Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. JAAPA 2022; 35:21-27. [PMID: 34908560 DOI: 10.1097/01.jaa.0000803620.44399.46] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
ABSTRACT Chronic thromboembolic pulmonary hypertension (CTEPH) remains significantly underdiagnosed in patients with a history of pulmonary embolism. These patients complain of persistent shortness of breath and present with hypoxemia despite proper anticoagulation. Further investigation reveals evidence of right ventricular dysfunction on echocardiogram, which progresses to right heart failure. CTEPH is associated with a significant increase in patient morbidity and mortality if left untreated. This article offers an approach for the timely recognition of this condition, in addition to suggesting a management protocol with an emphasis on the role of interventional radiology and balloon pulmonary angioplasty.
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Affiliation(s)
- Helwa Taweel
- At the Cleveland (Ohio) Clinic, Helwa Taweel practices in Interventional radiology, Ihab Haddadin is an interventional radiologist, and Gustavo Heresi is director of the pulmonary vascular and chronic thromboembolic pulmonary hypertension program. The authors have disclosed no potential conflicts of interest, financial or otherwise
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10
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Fathala A, Aldurabi A. Frequency of computed tomography abnormalities in patients with chronic thromboembolic pulmonary hypertension: a comparative study between lung perfusion scan and computed tomography pulmonary angiography. Multidiscip Respir Med 2021; 16:753. [PMID: 34322231 PMCID: PMC8273626 DOI: 10.4081/mrm.2021.753] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 05/31/2021] [Indexed: 12/12/2022] Open
Abstract
Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of pulmonary hypertension. Diagnosis of CTEPH can be established using various imaging techniques, including ventilation-perfusion scintigraphy (VQ) and multidetector computed tomography pulmonary angiography (CTPA). The aim of this study was to determine the frequency of direct pulmonary vascular, parenchymal lung, and cardiac abnormalities on CTPA in patients with CTEPH and to compare the diagnostic accuracy of both VQ scan CTPA in detecting CTEPH. Methods We retrospectively included 54 patients who had been referred for pulmonary hypertension service (20 males, 34 females). All patients had VQ scan and CTPA within 15 days and underwent pulmonary artery endarterectomy (PEA) thereafter. VQ scans were reported according to modified PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) criteria. CTPA was considered as diagnostic for CTEPH if it showed presence of thrombus, webs, stenosis, or perfusion lung abnormalities. Results The mean age of the study population was 41±10 years. The mean pulmonary artery pressure was 53±13 mmHg. Fifty-three out of 54 patients in the study population had high probability VQ scan and one patient had intermediate probability. CTPA was suggestive of CTEPH in all patients. The most frequent CTPA findings in the central pulmonary arteries and peripheral arteries were presence of thrombotic materials, abnormal vessel tapering and abrupt vessels-cut off (76% vs 65%, 67% vs 48%, and 48% vs 22%), respectively. The mosaic lung perfusion was present in 78% of the patients, and various cardiac morphology abnormalities were present and most common was abnormal right to left ventricle ratio (69%). Conclusion Our findings indicate that both VQ scan and CTPA are highly sensitive for the detection of CTEPH confirmed by PEA. Most CTEPH patients had several pulmonary vascular, parenchymal lung and cardiac abnormalities. There was no sign with 100% sensitivity on CTPA for CTEPH detection.
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Affiliation(s)
- Ahmed Fathala
- Department of Radiology, Nuclear Medicine and Cardiovascular Imaging, King Faisal Specialist Hospital and Research Center, Riyadh
| | - Alaa Aldurabi
- Department of Radiology, College of Medicine, Qassim University, Buraidah, Saudi Arabia
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11
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Alba GA, Samokhin AO, Wang RS, Zhang YY, Wertheim BM, Arons E, Greenfield EA, Lundberg Slingsby MH, Ceglowski JR, Haley KJ, Bowman FP, Yu YR, Haney JC, Eng G, Mitchell RN, Sheets A, Vargas SO, Seo S, Channick RN, Leary PJ, Rajagopal S, Loscalzo J, Battinelli EM, Maron BA. NEDD9 Is a Novel and Modifiable Mediator of Platelet-Endothelial Adhesion in the Pulmonary Circulation. Am J Respir Crit Care Med 2021; 203:1533-1545. [PMID: 33523764 PMCID: PMC8483217 DOI: 10.1164/rccm.202003-0719oc] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 01/29/2021] [Indexed: 12/16/2022] Open
Abstract
Rationale: Data on the molecular mechanisms that regulate platelet-pulmonary endothelial adhesion under conditions of hypoxia are lacking, but may have important therapeutic implications. Objectives: To identify a hypoxia-sensitive, modifiable mediator of platelet-pulmonary artery endothelial cell adhesion and thrombotic remodeling. Methods: Network medicine was used to profile protein-protein interactions in hypoxia-treated human pulmonary artery endothelial cells. Data from liquid chromatography-mass spectrometry and microscale thermophoresis informed the development of a novel antibody (Ab) to inhibit platelet-endothelial adhesion, which was tested in cells from patients with chronic thromboembolic pulmonary hypertension (CTEPH) and three animal models in vivo. Measurements and Main Results: The protein NEDD9 was identified in the hypoxia thrombosome network in silico. Compared with normoxia, hypoxia (0.2% O2) for 24 hours increased HIF-1α (hypoxia-inducible factor-1α)-dependent NEDD9 upregulation in vitro. Increased NEDD9 was localized to the plasma-membrane surface of cells from control donors and patients with CTEPH. In endarterectomy specimens, NEDD9 colocalized with the platelet surface adhesion molecule P-selectin. Our custom-made anti-NEDD9 Ab targeted the NEDD9-P-selectin interaction and inhibited the adhesion of activated platelets to pulmonary artery endothelial cells from control donors in vitro and from patients with CTEPH ex vivo. Compared with control mice, platelet-pulmonary endothelial aggregates and pulmonary hypertension induced by ADP were decreased in NEDD9-/- mice or wild-type mice treated with the anti-NEDD9 Ab, which also decreased chronic pulmonary thromboembolic remodeling in vivo. Conclusions: The NEDD9-P-selectin protein-protein interaction is a modifiable target with which to inhibit platelet-pulmonary endothelial adhesion and thromboembolic vascular remodeling, with potential therapeutic implications for patients with disorders of increased hypoxia signaling pathways, including CTEPH.
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Affiliation(s)
- George A Alba
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, and
| | - Andriy O Samokhin
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
| | - Rui-Sheng Wang
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
| | - Ying-Yi Zhang
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Elena Arons
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
| | | | | | | | | | - Frederick P Bowman
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
| | - Yen-Rei Yu
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
| | - John C Haney
- Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
| | - George Eng
- Division of Pulmonary and Critical Care Medicine, Department of Medicine
| | - Richard N Mitchell
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, and
| | - Anthony Sheets
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, and
| | - Sara O Vargas
- Division of Cardiology, Department of Medicine, Duke University Medical Center, Duke University, Durham, North Carolina
| | - Sachiko Seo
- Department of Pathology, Boston Children's Hospital, Boston, Massachusetts
| | - Richard N Channick
- Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan
| | - Peter J Leary
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Ronald Reagan UCLA Medical Center, University of California, Los Angeles, Los Angeles, California; and
| | - Sudarshan Rajagopal
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, Washington
| | - Joseph Loscalzo
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - Bradley A Maron
- Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts
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12
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Tanabe N, Fukuda K, Matsubara H, Nakanishi N, Tahara N, Ikeda S, Kishi T, Satoh T, Hirata KI, Inoue T, Kimura H, Okano Y, Okazaki O, Sata M, Tsujino I, Ueno S, Yamada N, Yao A, Kuriyama T. Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients - A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study. Circ J 2020; 84:1866-1874. [PMID: 32879152 DOI: 10.1253/circj.cj-20-0438] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index. CONCLUSIONS Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).
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Affiliation(s)
- Nobuhiro Tanabe
- Department of Respirology, Graduate School of Medicine, Chiba University
| | - Keiichi Fukuda
- Department of Cardiology, Keio University School of Medicine
| | - Hiromi Matsubara
- Director of Entire Medical Departments, National Hospital Organization Okayama Medical Center
| | | | - Nobuhiro Tahara
- Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine
| | - Satoshi Ikeda
- Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences
| | - Takuya Kishi
- Department of Cardiology, Graduate School of Medical Sciences, International University of Health and Welfare
| | - Toru Satoh
- Department of Cardiovascular Medicine, Kyorin University Hospital
| | - Ken-Ichi Hirata
- Cardiovascular Medicine, Kobe University Graduate School of Medicine
| | - Teruo Inoue
- Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine
| | | | - Yoshiaki Okano
- Department of Intermal Medicine, Hanwa Dai-ni Senboku Hospital
| | - Osamu Okazaki
- Department of Cardiology, National Center for Global Health and Medecine
| | - Masataka Sata
- Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences
| | - Ichizo Tsujino
- The First Department of Medicine, Hokkaido University School of Medicine
| | - Shuichi Ueno
- Department of Internal Medicine Division of Cardiovascular Medicine, Jichi Medical University School of Medicine
- Ueno Clinic
| | | | - Atsushi Yao
- Department of Cardiovascular Medicine, The University of Tokyo Hospital
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Tanabe N, Ogo T, Hatano M, Kigawa A, Sunaya T, Sato S. Safety and effectiveness of riociguat for chronic thromboembolic pulmonary hypertension in real-world clinical practice: interim data from post-marketing surveillance in Japan. Pulm Circ 2020; 10:2045894020938986. [PMID: 32754307 PMCID: PMC7378726 DOI: 10.1177/2045894020938986] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 05/22/2020] [Indexed: 12/24/2022] Open
Abstract
This multicenter, prospective, non-interventional study (ClinicalTrials.gov:
NCT02117791) evaluated the safety and effectiveness of riociguat for chronic
thromboembolic pulmonary hypertension in Japanese clinical practice, registering
all patients with chronic thromboembolic pulmonary hypertension treated with
riociguat following its launch in Japan in April 2014. Safety was assessed by
analyzing the adverse drug reactions. Effectiveness measurements included the
assessment of change in World Health Organization functional class, six-minute
walk test, and hemodynamics. Overall, 1031 patients were included in the safety
analysis with 811 (78.7%) patients in World Health Organization functional class
II/III. The mean treatment duration was 591.4 days (median 441.0 days). Adverse
drug reactions were reported in 19.5% of patients, the most common being
hypotension (5.9%), headache (3.0%), dizziness (1.9%), and gastroesophageal
reflux disease (1.5%). Serious adverse drug reactions were reported in 2.1% of
patients. Estimated survival was 97.0% at one year, 95.8% at two years, and
94.4% at three years. The effectiveness analysis (n = 1027)
showed significant increases from baseline in six-minute walking distance, and
significant reductions from baseline in mean pulmonary arterial pressure and
pulmonary vascular resistance. These interim results of riociguat in Japanese
patients with chronic thromboembolic pulmonary hypertension demonstrated a
safety profile that was generally consistent with those of pivotal clinical
studies. The study is ongoing, and will continue to provide insights into the
safety and effectiveness of riociguat in real-world practice.
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Affiliation(s)
| | - Takeshi Ogo
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Masaru Hatano
- Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Ayaka Kigawa
- Medical Affairs Pulmonology and Cardiology, Bayer Yakuhin, Ltd, Osaka, Japan
| | - Toshiyuki Sunaya
- Data Sciences and Analytics, Research and Development Japan, Bayer Yakuhin, Ltd, Osaka, Japan
| | - Shoichiro Sato
- Pharmacovigilance and Medical Governance, Medical Affairs, Bayer Yakuhin, Ltd, Osaka, Japan
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14
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Moradi F, Morris TA, Hoh CK. Perfusion Scintigraphy in Diagnosis and Management of Thromboembolic Pulmonary Hypertension. Radiographics 2020; 39:169-185. [PMID: 30620694 DOI: 10.1148/rg.2019180074] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication of acute pulmonary embolism (PE). Because the treatment of CTEPH is markedly different from that of other types of pulmonary hypertension, lung ventilation-perfusion (V/Q) scintigraphy is recommended for the workup of patients with unexplained pulmonary hypertension. Lung V/Q scintigraphy is superior to CT pulmonary angiography for detecting CTEPH. Perfusion defect findings of CTEPH can be different from those of acute PE. Familiarity with the patterns of perfusion defects seen during the initial workup of CTEPH and the expected posttreatment changes seen at follow-up imaging is essential for accurate interpretation of V/Q scintigraphy findings. ©RSNA, 2019.
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Affiliation(s)
- Farshad Moradi
- From the Department of Radiology, Division of Nuclear Medicine (F.M., C.K.H.); and Division of Pulmonary, Critical Care, and Sleep Medicine (T.A.M.), University of California, San Diego, San Diego, Calif
| | - Timothy A Morris
- From the Department of Radiology, Division of Nuclear Medicine (F.M., C.K.H.); and Division of Pulmonary, Critical Care, and Sleep Medicine (T.A.M.), University of California, San Diego, San Diego, Calif
| | - Carl K Hoh
- From the Department of Radiology, Division of Nuclear Medicine (F.M., C.K.H.); and Division of Pulmonary, Critical Care, and Sleep Medicine (T.A.M.), University of California, San Diego, San Diego, Calif
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15
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Sepúlveda C, Repolho D, Antunes AM, Taulaigo AV, Carreiro F, Ferreira RC, Moraes-Fontes MF, Loureiro MJ. Dyspnea in antiphospholipid syndrome: Beyond pulmonary embolism. Rev Port Cardiol 2020; 39:47.e1-47.e5. [PMID: 32173092 DOI: 10.1016/j.repc.2018.01.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Accepted: 01/15/2018] [Indexed: 11/15/2022] Open
Abstract
Pulmonary embolism due to primary antiphospholipid syndrome is rarely associated with chronic thromboembolic pulmonary hypertension, and therefore according to the latest guidelines on pulmonary hypertension, routine screening is not recommended. We describe a young patient with a late diagnosis of chronic thromboembolic pulmonary hypertension in the context of pulmonary embolism, primary antiphospholipid syndrome and suboptimal anticoagulation. Of note, mild cardiopulmonary symptoms were consistently misattributed to a depressive disorder because physical examination was normal, serial Doppler echocardiography failed to show pulmonary hypertension, and all other diagnostic tests were normal. Once symptoms became severe, positive screening tests led to the correct diagnosis and surgical referral, and bilateral pulmonary endarterectomy was successfully performed. This case demonstrates the need for extra awareness in patients with antiphospholipid syndrome and pulmonary embolism.
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Affiliation(s)
- Carolina Sepúlveda
- Unidade de Doenças Autoimunes, Medicina 7.2, Hospital Curry Cabral - Centro Hospitalar Lisboa Central (CHLC), Lisboa, Portugal; Serviço de Medicina Interna, Hospital de Abrantes - Centro Hospitalar Médio Tejo (CHMT), Abrantes, Portugal.
| | - Débora Repolho
- Unidade de Hipertensão Pulmonar, Serviço de Cardiologia - Hospital Garcia de Orta (HGO), Almada, Portugal
| | - Ana Margarida Antunes
- Unidade de Doenças Autoimunes, Medicina 7.2, Hospital Curry Cabral - Centro Hospitalar Lisboa Central (CHLC), Lisboa, Portugal
| | - Anna Viola Taulaigo
- Unidade de Doenças Autoimunes, Medicina 7.2, Hospital Curry Cabral - Centro Hospitalar Lisboa Central (CHLC), Lisboa, Portugal
| | - Filipa Carreiro
- Unidade de Doenças Autoimunes, Medicina 7.2, Hospital Curry Cabral - Centro Hospitalar Lisboa Central (CHLC), Lisboa, Portugal; Serviço de Medicina Interna - Hospital do Divino Espírito Santo (HDES), Ponta Delgada, Portugal
| | - Rui Cruz Ferreira
- Serviço de Cardiologia, Hospital de Santa Marta - CHLC, Lisboa, Portugal
| | - Maria Francisca Moraes-Fontes
- Unidade de Doenças Autoimunes, Medicina 7.2, Hospital Curry Cabral - Centro Hospitalar Lisboa Central (CHLC), Lisboa, Portugal
| | - Maria José Loureiro
- Unidade de Hipertensão Pulmonar, Serviço de Cardiologia - Hospital Garcia de Orta (HGO), Almada, Portugal
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16
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Sepúlveda C, Repolho D, Antunes AM, Taulaigo AV, Carreiro F, Ferreira RC, Moraes-Fontes MF, Loureiro MJ. Dyspnea in antiphospholipid syndrome: Beyond pulmonary embolism. REVISTA PORTUGUESA DE CARDIOLOGIA (ENGLISH EDITION) 2020. [DOI: 10.1016/j.repce.2018.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Narechania S, Renapurkar R, Heresi GA. Mimickers of chronic thromboembolic pulmonary hypertension on imaging tests: a review. Pulm Circ 2020; 10:2045894019882620. [PMID: 32257112 PMCID: PMC7103595 DOI: 10.1177/2045894019882620] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 09/21/2019] [Indexed: 12/20/2022] Open
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by mechanical obstruction of large pulmonary arteries secondary to one or more episodes of pulmonary embolism. Ventilation perfusion scan is the recommended initial screening test for this condition and typically shows multiple large mismatched perfusion defects. However, not all patients with an abnormal ventilation perfusion scan have CTEPH since there are other conditions that be associated with a positive ventilation perfusion scan. These conditions include in situ thrombosis, pulmonary artery sarcoma, fibrosing mediastinitis, pulmonary vasculitis and sarcoidosis, among others. Although these conditions cannot be distinguished from CTEPH using a ventilation perfusion scan, they have certain characteristic radiological features that can be demonstrated on other imaging techniques such as computed tomography scan and can help in differentiation of these conditions. In this review, we have summarized some key clinical and radiological features that can help differentiate CTEPH from the CTEPH mimics.
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Affiliation(s)
| | - Rahul Renapurkar
- Department of Diagnostic Radiology,
Cleveland
Clinic, Cleveland, OH, USA
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18
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Zhang Y, Wu M, Cao Y, Guo F, Li Y. Linking lncRNAs to regulation, pathogenesis, and diagnosis of pulmonary hypertension. Crit Rev Clin Lab Sci 2019:1-15. [PMID: 31738606 DOI: 10.1080/10408363.2019.1688760] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Pulmonary hypertension (PH) is a syndrome characterized by a persistent increase in pulmonary vascular resistance. Due to the lack of specificity in clinical manifestations, patients are usually diagnosed at the late stage of PH, which is hard to treat and often causes right heart failure and death. Furthermore, the regulation and pathogenesis of PH remain obscure. Recently, long noncoding RNAs (lncRNAs), a type of transcript longer than 200 nt that lacks protein-coding ability, have been found to substantially influence the incidence and progression of various diseases through regulating gene expression at the chromatin, transcriptional, post-transcriptional, translational, and even post-translational levels. The crucial roles of lncRNAs in PH have started to draw widespread attention. This review summarizes the regulatory, pathogenic, and diagnostic roles of lncRNAs in PH, in the hope to facilitate the search for early diagnostic markers of and effective therapeutic targets for this devastating disease.
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Affiliation(s)
- Yan Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Medical University Eye Hospital, School of Optometry and Ophthalmology & Eye Institute, Tianjin, China
| | - Mianmian Wu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Medical University Eye Hospital, School of Optometry and Ophthalmology & Eye Institute, Tianjin, China
| | - Yunshan Cao
- Department of Cardiology, Gansu Provincial Hospital, Lanzhou University, Lanzhou, China
| | - Fang Guo
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Medical University Eye Hospital, School of Optometry and Ophthalmology & Eye Institute, Tianjin, China
| | - Yahong Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Medical University Eye Hospital, School of Optometry and Ophthalmology & Eye Institute, Tianjin, China
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19
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Indications and potential pitfalls of anticoagulants in pulmonary hypertension: Would DOACs become a better option than VKAs? Blood Rev 2019; 37:100579. [DOI: 10.1016/j.blre.2019.05.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 04/29/2019] [Accepted: 05/14/2019] [Indexed: 01/23/2023]
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Jacqueroux E, Mercier C, Margelidon‐Cozzolino V, Hodin S, Bertoletti L, Delavenne X. In vitro assessment of P‐gp and BCRP transporter‐mediated drug–drug interactions of riociguat with direct oral anticoagulants. Fundam Clin Pharmacol 2019; 34:109-119. [DOI: 10.1111/fcp.12504] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 07/19/2019] [Accepted: 08/12/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Elodie Jacqueroux
- INSERM U1059 Laboratoire Sainbiose Equipe Dysfonctions Vasculaires et Hémostase Faculté de médecine de Saint‐Etienne Université de Lyon F‐42055 Saint‐Etienne France
| | - Clément Mercier
- INSERM U1059 Laboratoire Sainbiose Equipe Dysfonctions Vasculaires et Hémostase Faculté de médecine de Saint‐Etienne Université de Lyon F‐42055 Saint‐Etienne France
| | - Victor Margelidon‐Cozzolino
- INSERM U1059 Laboratoire Sainbiose Equipe Dysfonctions Vasculaires et Hémostase Faculté de médecine de Saint‐Etienne Université de Lyon F‐42055 Saint‐Etienne France
| | - Sophie Hodin
- INSERM U1059 Laboratoire Sainbiose Equipe Dysfonctions Vasculaires et Hémostase Faculté de médecine de Saint‐Etienne Université de Lyon F‐42055 Saint‐Etienne France
| | - Laurent Bertoletti
- INSERM U1059 Laboratoire Sainbiose Equipe Dysfonctions Vasculaires et Hémostase Faculté de médecine de Saint‐Etienne Université de Lyon F‐42055 Saint‐Etienne France
- Service de Médecine Vasculaire et Thérapeutique CHU de Saint‐Etienne F‐42055 Saint‐Etienne France
| | - Xavier Delavenne
- INSERM U1059 Laboratoire Sainbiose Equipe Dysfonctions Vasculaires et Hémostase Faculté de médecine de Saint‐Etienne Université de Lyon F‐42055 Saint‐Etienne France
- Laboratoire de Pharmacologie Toxicologie CHU de Saint‐Etienne F‐42055 Saint‐Etienne France
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21
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Watanabe K, Ito N, Ohata T, Kariya T, Inui H, Yamada Y. Preoperative balloon pulmonary angioplasty enabled noncardiac surgery of a patient with chronic thromboembolic pulmonary hypertension (CTEPH): A case report. Medicine (Baltimore) 2019; 98:e14807. [PMID: 30855499 PMCID: PMC6417548 DOI: 10.1097/md.0000000000014807] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
RATIONALE Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease with a poor prognosis, characterized by chronic thromboembolic obstruction of the pulmonary arteries and pulmonary hypertension. Balloon pulmonary angioplasty (BPA) is a newly emergent treatment for CTEPH, which may substitute pulmonary endarterectomy, the standard but more invasive treatment for CTEPH. Here, we report the case of a CTEPH patient who underwent 2 noncardiac surgeries without complications after preoperative intervention of BPA. PATIENT CONCERNS A 79-year-old man presented with severe osteoarthritis of bilateral knees, with adaptation of total knee arthroplasty (TKA). Transthoracic echocardiogram revealed severe pulmonary hypertension with estimated right ventricular systolic pressure of 140 mm Hg. DIAGNOSIS Pulmonary arteriography revealed total occlusion of the upper branch of the right pulmonary artery, and ventilation/perfusion scan showed multiple mismatched perfusion defects. His pulmonary artery pressure (PAP) was as high as 89/25 (46) mm Hg with normal range of pulmonary capillary wedge pressure. He was diagnosed with CTEPH. INTERVENTIONS Four BPA sessions for 8 branches of the bilateral pulmonary arteries were done, until the mean PAP (mPAP) went under 30 mm Hg. For the TKA, we selected spinal anesthesia in order to minimize intraoperative hemodynamic changes. Cardiac surgeons were standby in case extracorporeal membrane oxygenation (ECMO) initiation was required. OUTCOMES With appropriate pain management and use of intravenous vasopressors, intraoperative vital signs were stable. No symptoms of hemodynamic collapse were observed postoperatively. The patient was discharged on the 46th postoperative day following rehabilitation. Two years later, left-side unicompartment knee arthroplasty (UKA) was scheduled. Right heart catheterization study revealed the mPAP was 30 mm Hg, nearly the same value as the last study. The operation was performed under spinal anesthesia with continuous arterial pressure monitoring without need for intraoperative vasopressor. He was discharged without complications on the 24th postoperative day. LESSONS BPA can be an effective preoperative intervention for CTEPH patients undergoing noncardiac surgery.
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Affiliation(s)
- Kenji Watanabe
- Department of Anesthesiology, Faculty of Medicine, The University of Tokyo, Tokyo
- Department of Anesthesia, New Tokyo Hospital, Chiba
| | - Nobuko Ito
- Department of Anesthesiology, Faculty of Medicine, The University of Tokyo, Tokyo
| | - Takuya Ohata
- Department of Anesthesiology, Faculty of Medicine, The University of Tokyo, Tokyo
| | - Taro Kariya
- Department of Anesthesiology, Faculty of Medicine, The University of Tokyo, Tokyo
| | - Hiroshi Inui
- Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshitsugu Yamada
- Department of Anesthesiology, Faculty of Medicine, The University of Tokyo, Tokyo
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Trammell AW, Shah AJ, Phillips LS, Michael Hart C. Mortality in US veterans with pulmonary hypertension: a retrospective analysis of survival by subtype and baseline factors. Pulm Circ 2019; 9:2045894019825763. [PMID: 30638433 DOI: 10.1177/2045894019825763] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Pulmonary hypertension (PH) occurs when the pulmonary vasculature is itself diseased or becomes affected secondarily by comorbid conditions, commonly left heart or lung disease. The high prevalence of chronic cardiopulmonary conditions among patients served by Veterans Health Administration (VHA) suggests this population may be particularly susceptible to PH. We sought to identify clinical features and outcomes in veterans diagnosed with PH. We utilized the VHA Corporate Data Warehouse to identify veterans diagnosed between January 1, 2003 and September 30, 2015, assess relevant patient characteristics and their survival time. The effects of PH subtype and baseline factors on outcome were estimated by Cox modeling. There were 110,564 veterans diagnosed with PH during the study period. These veterans were predominantly male, had median age 70.2, and had a high burden of comorbid conditions. PH was frequently due to left heart and/or lung disease. Average survival after PH diagnosis was 3.88 years. Compared with other types, PH due to left heart disease, lung disease or both had shorter survival. This large retrospective study of veterans demonstrates the significance of PH due to left heart and/or lung disease which was common and had high risk of death. Multi-comorbidity was common and added to risk. These findings underscore the need for risk assessment tools for subjects with non-Group 1 PH and novel management strategies to improve their outcome. This study details the largest retrospective cohort assembled for evaluation of secondary PH and allows hypothesis-generating inquiries into these common conditions that are rarely prospectively studied.
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Affiliation(s)
- Aaron W Trammell
- 1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
- 2 Atlanta VA Medical Center, Decatur, Georgia, USA
| | - Amit J Shah
- 2 Atlanta VA Medical Center, Decatur, Georgia, USA
- 3 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Lawrence S Phillips
- 2 Atlanta VA Medical Center, Decatur, Georgia, USA
- 4 Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - C Michael Hart
- 1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
- 2 Atlanta VA Medical Center, Decatur, Georgia, USA
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Li C, Zhao J, Liu S, Song W, Zhu J, Hua L, Wang Q, Li M, Zeng X, Zhao Y. Pulmonary thromboendarterectomy is a curative resolution for chronic thromboembolic pulmonary hypertension associated with antiphospholipid syndrome: a retrospective cohort study. Lupus 2018; 27:2206-2214. [PMID: 30451640 DOI: 10.1177/0961203318810427] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening condition with poor prognosis in patients with antiphospholipid syndrome (APS). Pulmonary thromboendarterectomy (PTE) is the optimal surgical option for CTEPH. Objectives This retrospective cohort study aimed to evaluate the efficacy and risk of PTE in patients with APS-associated CTEPH. Methods Consecutive patients with APS-associated CTEPH diagnosed between January 2012 and September 2017 at Peking Union Medical College Hospital were retrospectively evaluated. Demographics, clinical manifestations, antiphospholipid antibody (aPL) profiles, and pulmonary arterial hypertension–targeted medications were collected. Deterioration of cardiac function and death were chosen as the endpoints, in order to assess the effect of PTE on short-term and long-term prognoses (evaluated by the change of cardiac function after treatment and cardiac deterioration or death in the follow-up, respectively). Results A total of 20 patients with APS-associated CTEPH were enrolled, and eight patients underwent PTE. Chi-square test ( p = 0.01) and Kaplan–Meier curves (log rank test, p = 0.04) showed that there were statistically significant differences in both short-term and long-term prognoses between patients with and without PTE. Conclusion These results provide strong evidence that PTE is a curative resolution in patients with APS-associated CTEPH. Following a full specialized and multidisciplinary risk-benefit evaluation to limit the risk of thrombosis or bleeding and to manage possible thrombocytopenia, PTE is at least a temporal curative resolution for CTEPH complicated with APS.
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Affiliation(s)
- C Li
- Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China
| | - J Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China
| | - S Liu
- Department of Cardiac Surgery, Fu Wai Hospital, Chinese Academy of Medical Science, Beijing, China
| | - W Song
- Department of Cardiac Surgery, Fu Wai Hospital, Chinese Academy of Medical Science, Beijing, China
| | - J Zhu
- Department of Cardiac Surgery, Fu Wai Hospital, Chinese Academy of Medical Science, Beijing, China
| | - L Hua
- Department of Cardiac Surgery, Fu Wai Hospital, Chinese Academy of Medical Science, Beijing, China
| | - Q Wang
- Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China
| | - M Li
- Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China
| | - X Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China
| | - Y Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China
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Abstract
PURPOSE OF REVIEW Acute pulmonary embolism is a major cause of morbidity and mortality in the USA and throughout the world. This review will summarize recent developments in short- and long-term mortality risk assessment after an acute pulmonary embolism. RECENT FINDINGS Recent guidelines have emphasized risk stratification of acute PE patients on the basis of blood pressure, right ventricular size, and biomarker status. Ongoing work is testing various acute treatment strategies for improvement of symptom burden, length of stay, quality of life, and possibly mortality risk reduction. Long-term outcomes among subjects with acute PE are less well studied. Long-term mortality largely correlates with baseline co-morbidity burden, although there may be an association between acute PE severity and long-term outcomes. Acute PE risk stratification and treatment, as well as long-term follow-up of patients with acute PE, are rapidly developing areas and many promising innovations are underway.
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Menon K, Sutphin PD, Bartolome S, Kalva SP, Ogo T. Chronic thromboembolic pulmonary hypertension: emerging endovascular therapy. Cardiovasc Diagn Ther 2018; 8:272-278. [PMID: 30057875 DOI: 10.21037/cdt.2018.06.07] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating but potentially reversible complication of chronic pulmonary thromboembolic disease characterized by progressive right heart dysfunction secondary to pulmonary arterial stenosis or occlusion. Balloon pulmonary angioplasty (BPA) has recently emerged as an alternative intervention for non-surgical candidates with CTEPH. Modern reperfusion angioplasty techniques relieve sequela of chronic pulmonary hypertension, ameliorate right ventricular failure, and improve functional status. This article will discuss the diagnosis and treatment of patients with CTEPH and the current state of endovascular management with BPA.
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Affiliation(s)
- Keshav Menon
- Department of Interventional Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Patrick D Sutphin
- Department of Interventional Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Sonja Bartolome
- Department of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Sanjeeva P Kalva
- Department of Interventional Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Takeshi Ogo
- Department of Advanced Medicine for Pulmonary Hypertension, National Cerebral and Cardiovascular Centre, Osaka, Japan
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Nishiyama KH, Saboo SS, Tanabe Y, Jasinowodolinski D, Landay MJ, Kay FU. Chronic pulmonary embolism: diagnosis. Cardiovasc Diagn Ther 2018; 8:253-271. [PMID: 30057874 DOI: 10.21037/cdt.2018.01.09] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of venous thromboembolic disease. Differently from other causes of pulmonary hypertension, CTEPH is potentially curable with surgery (thromboendarterectomy) or balloon pulmonary angioplasty. Imaging plays a central role in CTEPH diagnosis. The combination of techniques such as lung scintigraphy, computed tomography and magnetic resonance angiography provides non-invasive anatomic and functional information. Conventional pulmonary angiography (CPA) with right heart catheterization (RHC) is considered the gold standard method for diagnosing CTEPH. In this review, we discuss the utility of these imaging techniques in the diagnosis of CTEPH.
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Affiliation(s)
- Katia Hidemi Nishiyama
- Department of Thoracic Imaging, Hospital do Coração and DASA (Diagnósticos da América), São Paulo, Brazil
| | - Sachin S Saboo
- Department of Radiology, UT Southwestern Medical Center, Florence Building, Dallas, TX, USA
| | - Yuki Tanabe
- Department of Radiology, UT Southwestern Medical Center, Florence Building, Dallas, TX, USA
| | | | - Michael J Landay
- Department of Radiology, UT Southwestern Medical Center, Florence Building, Dallas, TX, USA
| | - Fernando Uliana Kay
- Department of Radiology, UT Southwestern Medical Center, Florence Building, Dallas, TX, USA
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Benza RL, Farber HW, Frost A, Grünig E, Hoeper MM, Busse D, Meier C, Nikkho S, Ghofrani HA. REVEAL risk score in patients with chronic thromboembolic pulmonary hypertension receiving riociguat. J Heart Lung Transplant 2018; 37:836-843. [PMID: 29580746 DOI: 10.1016/j.healun.2018.02.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 02/23/2018] [Accepted: 02/23/2018] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND The REVEAL risk score (RRS) was developed to predict survival in patients with pulmonary arterial hypertension (PAH), based on multiple patient characteristics. Herein we calculated RRS for patients in the randomized CHEST-1 study and open-label CHEST-2 extension study of riociguat in inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). We investigated the effect of riociguat vs placebo on RRS in the CHEST-1 study, and the relationship between RRS and long-term outcomes in the CHEST-2 study. METHODS RRS was calculated post hoc for baseline and Week 16 of CHEST-1 and Week 12 of CHEST-2, based on 9 evaluable elements. Patients were grouped into risk strata by RRS. Relationships between RRS and both survival and clinical worsening-free survival were examined by Kaplan-Meier and Cox proportional hazards analyses. RESULTS Overall, 237 patients completed CHEST-1 and entered CHEST-2. In CHEST-1, riociguat significantly improved RRS (p < 0.0001) and risk stratum (p < 0.001) vs placebo from baseline to Week 16. RRS at baseline, and at Week 16, and change in RRS during CHEST-1 were significantly associated with survival (hazard ratios for a 1-point reduction in RRS: 0.702, 0.692, and 0.682, respectively) and clinical worsening-free survival (hazard ratios: 0.697, 0.719, and 0.754, respectively) over 2 years in CHEST-2. CONCLUSIONS Riociguat improved RRS in patients with inoperable and persistent/recurrent CTEPH. RRS at baseline and Week 16, and change in RRS from baseline, predicted survival and clinical worsening-free survival. This analysis of RRS in patients with inoperable or persistent/recurrent CTEPH suggests utility for the RRS in indications beyond PAH.
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Affiliation(s)
- Raymond L Benza
- Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA.
| | - Harrison W Farber
- Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA
| | - Adaani Frost
- Houston Methodist Hospital & Weill Cornell Medical College, Houston, Texas, USA
| | - Ekkehard Grünig
- Center for Pulmonary Hypertension, Thorax Clinic, University Hospital Heidelberg, Heidelberg, Germany
| | - Marius M Hoeper
- Clinic for Respiratory Medicine, Hannover Medical School, member of the German Center for Lung Research (DZL), Hannover, Germany
| | | | | | - Sylvia Nikkho
- Global Clinical Development, Bayer AG, Berlin, Germany
| | - Hossein-Ardeschir Ghofrani
- University of Giessen and Marburg Lung Center, member of the German Center for Lung Research (DZL), Giessen, Germany; Department of Medicine, Imperial College London, London, UK
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Iorianni C, Richter E. Anesthesia for Pulmonary Endarterectomy. Anesthesiology 2018. [DOI: 10.1007/978-3-319-74766-8_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Madani M, Ogo T, Simonneau G. The changing landscape of chronic thromboembolic pulmonary hypertension management. Eur Respir Rev 2017; 26:26/146/170105. [PMID: 29263176 PMCID: PMC9488650 DOI: 10.1183/16000617.0105-2017] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 11/25/2017] [Indexed: 01/09/2023] Open
Abstract
For patients with chronic thromboembolic pulmonary hypertension (CTEPH), the current standard of care involves surgical removal of fibro-thrombotic obstructions by pulmonary endarterectomy. While this approach has excellent outcomes, significant proportions of patients are not eligible for surgery or suffer from persistent/recurrent pulmonary hypertension after the procedure. The availability of balloon pulmonary angioplasty and the approval of the first medical therapy for use in CTEPH have significantly improved the outlook for patients ineligible for pulmonary endarterectomy. In this comprehensive review, we discuss the latest developments in the rapidly evolving field of CTEPH. These include improvements in imaging modalities and advances in surgical and interventional techniques, which have broadened the range of patients who may benefit from such procedures. The efficacy and safety of targeted medical therapies in CTEPH patients are also discussed, particularly the encouraging data from the recent MERIT-1 trial, which demonstrated the beneficial impact of using macitentan to treat patients with inoperable CTEPH, including those on background therapy. As the treatment options for CTEPH improve, hybrid management involving more than one intervention in the same patient may become a viable option in the near future. Management of CTEPH is evolving rapidly, leading to improved patient outcomeshttp://ow.ly/rHrt30gUQWX
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Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jaïs X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. THE LANCET. RESPIRATORY MEDICINE 2017; 5:785-794. [PMID: 28919201 DOI: 10.1016/s2213-2600(17)30305-3] [Citation(s) in RCA: 187] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 07/20/2017] [Accepted: 07/28/2017] [Indexed: 12/28/2022]
Abstract
BACKGROUND Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. FINDINGS Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 73·0% of baseline in the macitentan group and to 87·2% in the placebo group (geometric means ratio 0·84, 95% CI 0·70-0·99, p=0·041). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). INTERPRETATION In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. FUNDING Actelion Pharmaceuticals Ltd.
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Affiliation(s)
- Hossein-Ardeschir Ghofrani
- German Center for Lung Research (DZL), Giessen, Germany; University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; Department of Medicine, Imperial College London, London, UK.
| | - Gérald Simonneau
- Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France; INSERM U-999, Le Kremlin-Bicêtre, France
| | - Andrea M D'Armini
- Department of Cardio-Thoracic and Vascular Surgery, Heart and Lung Transplantation and Pulmonary Hypertension Unit, Foundation IRCCS Policlinico San Matteo, University of Pavia School of Medicine, Pavia, Italy
| | - Peter Fedullo
- Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, CA, USA
| | - Luke S Howard
- National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK; National Heart & Lung Institute, Imperial College London, London, UK
| | - Xavier Jaïs
- Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France; INSERM U-999, Le Kremlin-Bicêtre, France
| | - David P Jenkins
- Department of Cardiothoracic Surgery, Papworth Hospital, Cambridge, UK
| | - Zhi-Cheng Jing
- State Key Lab of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Michael M Madani
- Division of Cardiovascular and Thoracic Surgery, University of California San Diego Medical Center, San Diego, CA, USA
| | | | - Eckhard Mayer
- Department of Thoracic Surgery, Kerckhoff-Clinic, Bad Nauheim, Germany
| | | | | | - Nick H Kim
- Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, CA, USA
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Payares-Jardim C. Diagnóstico y tratamiento de la hipertensión pulmonar tromboembólica crónica. REVISTA COLOMBIANA DE CARDIOLOGÍA 2017. [DOI: 10.1016/j.rccar.2017.08.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Abstract
Pulmonary embolism is a major cause of mortality. Acute pulmonary embolism also encompasses a wide clinical spectrum of severity, ranging from asymptomatic silent disease to hemodynamic instability and shock. Echocardiography is a useful modality to improve treatment strategies for pulmonary embolus. Echocardiography plays a role in risk stratification at the time of diagnosis. The evaluation of the right ventricle (RV) has evolved over time. RV variables evaluated by echocardiography include RV size, RV/left ventricular ratio, RV fractional area of change, tricuspid annular plane systolic excursion, RV systolic pressure, and RV Tei index. It has also been used in determining treatment strategies and following the success of treatment. Multiple echocardiographic criteria have been studied to improve risk stratification and outcomes from pulmonary embolism. Further studies are needed to assess the appropriate quantitative echocardiographic parameters.
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Affiliation(s)
- Tanya Dutta
- From the Cardiology Division, Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY
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