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Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond
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Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Respiratory Medicine".

Deadline for manuscript submissions: closed (26 August 2022) | Viewed by 22540

Special Issue Editor

Dr. Andrea Dell'Amore

E-Mail Website
Guest Editor
Division of Thoracic Surgery, Padua University Hospital, 35128 Padua, Italy
Interests: heart transplantation; lung transplantation; heart and lung transplantation; pulmonary artery hypertension; pulmonary thromboendoarterctomy; ECMO; cardiac assistance devices; tracheal surgery; robotic surgery; minimally invasive cardiothoracic surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic pulmonary hypertension of thromboembolic origin represents a rare form of pulmonary hypertension, but it is certainly underestimated compared to the real incidence of this disease. Chronic thromboembolic pulmonary hypertension is one of the only diseases that can be treated surgically with an intervention known as pulmonary artery thromboendoarterectomy. This represents a complex intervention burdened by significant morbidity and mortality, but which is able to definitively recover from this disease. The correct surgical indication is essential to obtain good and long-lasting results. Alternatively, or in cases where surgery has not been feasible in the last few years, endovascular treatment methods have found their way, with equally good results. To date, drug therapy remains the least effective therapy for this form of pulmonary hypertension, but even in this field, progress is being made with the introduction of drugs that are more effective and that can be used in those patients who cannot be treated. in another way. Finally, lung transplantation and, more rarely, combined heart–lung transplantation can be considered the definitive therapy for this disease. The aim of this special monothematic edition is to treat this topic in an extensive way, starting from its epidemiology and etiopathogenesis and ending with the most modern therapeutic alterations in the treatment of chronic thromboembolic pulmonary hypertension.

Dr. Andrea Dell'Amore
Guest Editor

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Keywords

  • pulmonary artery hypertension
  • chronic thromboembolic pulmonary artery hypertension
  • right heart failure
  • pulmonary artery thromboendoarterectomy
  • acute pulmonary embolism
  • pulmonary catheterization
  • pulmonary artery angioplasty

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Published Papers (8 papers)

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Research

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11 pages, 3202 KiB  
Article
Effectiveness and Safety of Balloon Pulmonary Angioplasty for the Treatment of Patients with Persistent Pulmonary Hypertension after Pulmonary Endarterectomy
by Nicolas M. Maneiro Melon, Maite Velazquez Martin, Sergio Huertas Nieto, Agustin Albarran Gonzalez-Trevilla, Fernando Sarnago Cebada, Alejandro Cruz Utrilla, Williams Hinojosa Camargo, Ricardo Aguilar Colindres, Maria Melendo Viu, Maria Jesus Lopez Gude, Rafael Morales Ruiz, Marta Perez Nuñez, Fernando Arribas Ynsaurriaga and Pilar Escribano Subias
J. Clin. Med. 2023, 12(3), 905; https://doi.org/10.3390/jcm12030905 - 23 Jan 2023
Cited by 3 | Viewed by 2149
Abstract
(1) Background: Pulmonary endarterectomy (PEA) is the “gold standard” treatment for operable patients with chronic thromboembolic pulmonary hypertension (CTEPH). Persistent pulmonary hypertension (PH) after PEA confers a worse prognosis. Balloon pulmonary angioplasty (BPA) could represent a useful therapy in this setting, but evidence [...] Read more.
(1) Background: Pulmonary endarterectomy (PEA) is the “gold standard” treatment for operable patients with chronic thromboembolic pulmonary hypertension (CTEPH). Persistent pulmonary hypertension (PH) after PEA confers a worse prognosis. Balloon pulmonary angioplasty (BPA) could represent a useful therapy in this setting, but evidence about its effectiveness and safety in patients with previous PEA is limited. (2) Methods: A total of 14 patients with persistent PH after PEA were treated with BPA in a single PH center. Hemodynamic and clinical effects of BPA and complications of the procedure were retrospectively collected. (3) Results: After BPA, the mean pulmonary arterial pressure fell from 50.7 ± 15.3 mmHg to 38.0 ± 7.9 mmHg (25.0% decrease; 95% confidence interval (CI) 14.0–35.5%; p = 0.01). Pulmonary vascular resistances were reduced from 8.5 ± 3.6 WU to 5.3 ± 2.2 WU (37.6% decrease; 95% CI 18.8–56.5%; p = 0.01). WHO functional class was also improved with BPA. Severe BPA-related complications were infrequent and no periprocedural deaths were observed. (4) Conclusions: BPA is an effective and safe therapy for patients with CTEPH and persistent PH after PEA. Full article
(This article belongs to the Special Issue Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond)
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11 pages, 2386 KiB  
Article
Clinicopathological Correlation of Chronic Thromboembolic Pulmonary Hypertension: A Retrospective Study
by Ziyi Chang, Jixiang Liu, Bei Wang, Honglei Zhang, Ling Zhao, Yunchao Su, Wanmu Xie, Qiang Huang, Yanan Zhen, Fan Lin, Min Liu, Qian Gao, Wenyi Pang, Zhu Zhang, Han Tian, Yishan Li, Peiran Yang, Zhenguo Zhai and Dingrong Zhong
J. Clin. Med. 2022, 11(22), 6659; https://doi.org/10.3390/jcm11226659 - 10 Nov 2022
Cited by 1 | Viewed by 2706
Abstract
The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. Although pulmonary endarterectomy (PEA) is potentially curative, inoperable patients and persistent pulmonary hypertension (PH) following surgery remain a significant problem. In this study, we aim to describe the histopathological characteristics of CTEPH [...] Read more.
The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. Although pulmonary endarterectomy (PEA) is potentially curative, inoperable patients and persistent pulmonary hypertension (PH) following surgery remain a significant problem. In this study, we aim to describe the histopathological characteristics of CTEPH and explore the potential relationship between pulmonary arterial lesions, radiological parameters, and clinical manifestations. Endarterectomized tissues from 81 consecutive patients of CTEPH were carefully collected, sectioned, and examined by experienced pathologists. Pertinent clinical and radiological data were obtained from medical records and operative reports. Neointima, fresh/organized thrombi, recanalized regions, and atherosclerotic lesions were microscopically examined as previously described. Thrombi and atherosclerosis were dominant in UCSD classification level I PEA materials, while recanalized neo-vessels were more frequently observed in UCSD classification level III cases. Degenerative changes of the extracellular matrix were also noticed in the vascular bed. Atherosclerotic lesions were more frequently observed in cases with higher ratio of the pulmonary artery diameter to ascending aorta diameter (PA/AA) reflected by computed tomographic pulmonary arterial scanning. Furthermore, the removal of pulmonary artery complex lesions (with the combination of three to four types of lesions) by PEA was associated with lower postoperative mean pulmonary arterial pressure (mPAP) and decreased incidences of persistent PH. Our study demonstrates that the histopathological features of CTEPH are strongly linked with clinical manifestations and the postoperative outcome after PEA. These data may provide possible evidence for further studies in searching for appropriate causal factors underlying this disease. Full article
(This article belongs to the Special Issue Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond)
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12 pages, 953 KiB  
Article
The Impact of New Treatments on Short- and MID-Term Outcomes in Bilateral Lung Transplant: A Propensity Score Study
by Annalisa Boscolo, Andrea Dell’Amore, Tommaso Pettenuzzo, Nicolò Sella, Alessandro De Cassai, Elisa Pistollato, Nicola Cacco, Andrea Manzan, Agnese De Carolis, Federico Geraldini, Giulia Lorenzoni, Federica Pezzuto, Giovanni Zambello, Marco Schiavon, Fiorella Calabrese, Dario Gregori, Emanuele Cozzi, Federico Rea and Paolo Navalesi
J. Clin. Med. 2022, 11(19), 5859; https://doi.org/10.3390/jcm11195859 - 3 Oct 2022
Cited by 6 | Viewed by 1800
Abstract
Background: Despite many efforts to improve organ preservation and recipient survival, overall lung transplant (LT) mortality is still high. We aimed to investigate the impact of ‘prophylactic’ veno-arterial extracorporeal membrane oxygenation (VA ECMO) and tacrolimus on 72-h primary graft dysfunction (PGD) and 30-day [...] Read more.
Background: Despite many efforts to improve organ preservation and recipient survival, overall lung transplant (LT) mortality is still high. We aimed to investigate the impact of ‘prophylactic’ veno-arterial extracorporeal membrane oxygenation (VA ECMO) and tacrolimus on 72-h primary graft dysfunction (PGD) and 30-day acute cellular rejection, respectively. Methods: All consecutive LT patients admitted to the Intensive Care Unit of the Padua University Hospital (February, 2016–2022) were screened. Only adult patients undergoing first bilateral LT and not requiring cardio-pulmonary bypass, invasive mechanical ventilation, and/or ECMO before LT, were included. A propensity score weighting analysis was employed to account for the non-random allocation of the subjects to different treatments. Results: A total of 128 LT recipients were enrolled. Compared to the ‘off-pump’-group (n.47, 37%), ‘prophylactic’ VA ECMO (n.51,40%) recorded similar 72-h PGD values, perioperative blood products and lower acute kidney dysfunction. Compared with cyclosporine (n.86, 67%), tacrolimus (n.42, 33%) recorded a lower risk of 30-day cellular rejection, kidney dysfunction, and bacteria isolation. Conclusions: ‘Prophylactic’ VA ECMO recorded 72-h PGD values comparable to the ‘off-pump’-group; while tacrolimus showed a lower incidence of 30-day acute cellular rejection. Full article
(This article belongs to the Special Issue Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond)
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10 pages, 1285 KiB  
Article
Is Pulmonary Artery Pulsatility Index (PAPi) a Predictor of Outcome after Pulmonary Endarterectomy?
by Sofia Martin-Suarez, Gregorio Gliozzi, Giulio Giovanni Cavalli, Valentina Orioli, Antonio Loforte, Saverio Pastore, Barbara Rossi, Davide Zardin, Nazzareno Galiè, Massimiliano Palazzini, Fabio Dardi, Francesco Saia, Fabio Niro and Davide Pacini
J. Clin. Med. 2022, 11(15), 4353; https://doi.org/10.3390/jcm11154353 - 27 Jul 2022
Cited by 5 | Viewed by 2880
Abstract
Background: Pulmonary endarterectomy (PEA) is the gold standard therapy for chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally, pulmonary vascular resistance (PVR) represents the main prognostic factor after surgery. The pulmonary artery pulsatility index (PAPi) has been proposed for the assessment of RV in advanced [...] Read more.
Background: Pulmonary endarterectomy (PEA) is the gold standard therapy for chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally, pulmonary vascular resistance (PVR) represents the main prognostic factor after surgery. The pulmonary artery pulsatility index (PAPi) has been proposed for the assessment of RV in advanced heart failure, but it has never been applied in CTEPH patients. The aim of the present study is to describe PAPi in patients who underwent PEA, before and after surgery, and to define its predictive impact on postoperative outcomes. Methods: We retrospectively reviewed 188 consecutive adult patients who underwent PEA, between December 2003 and December 2021. PAPi was calculated for 186 patients and reported. Patients were partitioned in two groups using median preoperative PAPi as cutoff value: Group 1 with PAPi ≤ 8.6 (n = 94) and Group 2 with PAPi > 8.6 (n = 92). The propensity-score-matched analysis identified 67 pairs: Early outcomes were compared between two groups. Results: Mean preoperative PAPi was 10.3 ± 7.2. Considering matched populations, no differences emerged in terms of postoperative hemodynamics; Group 1 demonstrated higher 90-day mortality significance (10.4% vs. 3.0%, p = 0.082); the need for mechanical circulatory support (MCS) was similar, but successful weaning was unlikely (25% vs. 85.7%, p = 0.032). Conclusions: Mean PAPi in the CTEPH population is higher than in other diseases. Low PAPi (≤8.6) seems to be associated with lower postoperative survival and successful weaning from MCS. Full article
(This article belongs to the Special Issue Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond)
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Review

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19 pages, 1297 KiB  
Review
A Comprehensive Assessment of Right Ventricular Function in Chronic Thromboembolic Pulmonary Hypertension
by Stella Marchetta, Tom Verbelen, Guido Claessen, Rozenn Quarck, Marion Delcroix and Laurent Godinas
J. Clin. Med. 2023, 12(1), 47; https://doi.org/10.3390/jcm12010047 - 21 Dec 2022
Cited by 8 | Viewed by 2535
Abstract
While chronic thromboembolic pulmonary hypertension (CTEPH) results from macroscopic and microscopic obstruction of the pulmonary vascular bed, the function of the right ventricle (RV) and increased RV afterload are the main determinants of its symptoms and prognosis. In this review, we assess RV [...] Read more.
While chronic thromboembolic pulmonary hypertension (CTEPH) results from macroscopic and microscopic obstruction of the pulmonary vascular bed, the function of the right ventricle (RV) and increased RV afterload are the main determinants of its symptoms and prognosis. In this review, we assess RV function in patients diagnosed with CTEPH with a focus on the contributions of RV afterload and dysfunction to the pathogenesis of this disease. We will also discuss changes in RV function and geometry in response to treatment, including medical therapy, pulmonary endarterectomy, and balloon pulmonary angioplasty. Full article
(This article belongs to the Special Issue Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond)
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10 pages, 712 KiB  
Review
Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review of the Most Updated Literature
by Eleonora Faccioli, Vincenzo Verzeletti, Martina Perazzolo Marra, Annalisa Boscolo, Marco Schiavon, Paolo Navalesi, Federico Rea and Andrea Dell’Amore
J. Clin. Med. 2022, 11(23), 6976; https://doi.org/10.3390/jcm11236976 - 26 Nov 2022
Cited by 8 | Viewed by 2135
Abstract
Pulmonary endarterectomy (PEA) is the treatment of choice in case of chronic thromboembolic pulmonary hypertension (CTEPH). PEA is performed by an increasing number of surgeons; however, the reported outcomes are limited to a few registries or to individual centers’ experiences. This systematic review [...] Read more.
Pulmonary endarterectomy (PEA) is the treatment of choice in case of chronic thromboembolic pulmonary hypertension (CTEPH). PEA is performed by an increasing number of surgeons; however, the reported outcomes are limited to a few registries or to individual centers’ experiences. This systematic review focuses on pre-operative evaluation, intra-operative procedure and post-operative results in patients submitted to PEA for CTEPH. The literature included was searched using a formal strategy, combining the terms “pulmonary endarterectomy” AND “chronic pulmonary hypertension” and focusing on studies published in the last 5 years (2017–2022) to give a comprehensive overview on the most updated literature. The selection of the adequate surgical candidate is a crucial point, and the decision should always be performed by expert multidisciplinary teams composed of surgeons, pulmonologists and radiologists. In all the included studies, the surgical procedure was performed through a median sternotomy with intermittent deep hypothermic circulatory arrest under cardiopulmonary bypass. In case of residual pulmonary hypertension, alternative combined treatments should be considered (balloon angioplasty and/or medical therapy until lung transplantation in highly selected cases). Short- and long-term outcomes, although not homogenous across the different studies, are acceptable in highly experienced CTEPH centers. Full article
(This article belongs to the Special Issue Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond)
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11 pages, 4236 KiB  
Review
Clinical Presentations and Multimodal Imaging Diagnosis in Chronic Thromboembolic Pulmonary Hypertension
by Mi-Hyang Jung, Hae Ok Jung, Soo Jin Kwon and Suyon Chang
J. Clin. Med. 2022, 11(22), 6678; https://doi.org/10.3390/jcm11226678 - 10 Nov 2022
Cited by 4 | Viewed by 2730
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening pulmonary vascular disease caused by the presence of a prolonged thrombus in the pulmonary artery. CTEPH is a distinct disease entity classified as group 4 pulmonary hypertension according to the World Symposium on [...] Read more.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening pulmonary vascular disease caused by the presence of a prolonged thrombus in the pulmonary artery. CTEPH is a distinct disease entity classified as group 4 pulmonary hypertension according to the World Symposium on Pulmonary Hypertension. It is the only potentially curable cause of pulmonary hypertension. However, timely diagnosis and treatment are often hampered by nonspecific symptoms and signs and a lack of physician awareness regarding the condition. Thus, it is important to be familiar with the clinical features of CTEPH and the associated diagnostic processes. Herein, we cover the diagnostic approach for CTEPH using multimodal imaging tools in a clinical setting. Full article
(This article belongs to the Special Issue Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond)
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18 pages, 5851 KiB  
Review
Acute on Chronic Thromboembolic Pulmonary Hypertension: Case Series and Review of Management
by Isabelle Opitz, Miriam Patella, Olivia Lauk, Ilhan Inci, Dominique Bettex, Thomas Horisberger, Reto Schüpbach, Dagmar I. Keller, Thomas Frauenfelder, Nils Kucher, John Granton, Thomas Pfammatter, Marc de Perrot and Silvia Ulrich
J. Clin. Med. 2022, 11(14), 4224; https://doi.org/10.3390/jcm11144224 - 21 Jul 2022
Cited by 6 | Viewed by 4543
Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct form of precapillary pulmonary hypertension classified as group 4 by the World Symposium on Pulmonary Hypertension (WSPH) and should be excluded during an episode of acute pulmonary embolism (PE). Patients presenting to emergency departments with [...] Read more.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct form of precapillary pulmonary hypertension classified as group 4 by the World Symposium on Pulmonary Hypertension (WSPH) and should be excluded during an episode of acute pulmonary embolism (PE). Patients presenting to emergency departments with sudden onset of signs and symptoms of acute PE may already have a pre-existing CTEPH condition decompensated by the new PE episode. Identifying an underlying and undiagnosed CTEPH during acute PE, while challenging, is an important consideration as it will alter the patients’ acute and long-term management. Differential diagnosis and evaluation require an interdisciplinary expert team. Analysis of the clinical condition, the CT angiogram, and the hemodynamic situation are important considerations; patients with CTEPH usually have significantly higher sPAP at the time of index PE, which is unusual and unattainable in the context of acute PE and a naïve right ventricle. The imaging may reveal signs of chronic disease such as right ventricle hypertrophy bronchial collaterals and atypical morphology of the thrombus. There is no standard for the management of acute on chronic CTEPH. Herein, we provide a diagnostic and management algorithm informed by several case descriptions and a review of the literature. Full article
(This article belongs to the Special Issue Chronic Thromboembolic Pulmonary Hypertension: Medical, Surgical, Endovascular Treatment and Beyond)
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