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Pulmonary Arterial Hypertension: Old Drugs and New Treatment Strategies
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Pulmonary Arterial Hypertension: Old Drugs and New Treatment Strategies

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

Deadline for manuscript submissions: closed (10 October 2023) | Viewed by 8596

Special Issue Editor

Prof. Dr. Rosalinda Madonna

E-Mail Website
Guest Editor
Department of Pathology, University of Pisa, 56124 Pisa, Italy
Interests: cardio-oncology; heart failure; pulmonary hypertension; ischemia/reperfusion injury; cell therapy and cardiac stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pulmonary Hypertension (PH) is a hemodynamic condition characterized by an increase in pressure in the pulmonary artery secondary to various pathological conditions. A correct diagnosis and a correct clinical framing of PH are prerequisites for adequate treatment able to improve not only the symptoms and quality of life, but also the survival rates of patients. The implementation of aggressive therapy protocols focused on the combination of drugs with synergistic action from the beginning and the availability of new molecules acting on alternative cellular and molecular targets are now changing the outcomes of the disease, and are crucial challenges on which research and clinical practice must focus efforts and resources. In this Special Issue, we welcome authors to submit papers on the clinical advance of PH in terms of both diagnosis, risk assessment and treatment.

Prof. Dr. Rosalinda Madonna
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pulmonary hypertension
  • drugs
  • prostanoids
  • endothelin receptor antagonist
  • prostacyclin
  • cardiac imaging

Published Papers (6 papers)

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Editorial

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2 pages, 178 KiB  
Editorial
Pulmonary Arterial Hypertension in Genetic and Comorbid Settings: A Step Forward for Precision Medicine
by Rosalinda Madonna
J. Clin. Med. 2022, 11(22), 6671; https://doi.org/10.3390/jcm11226671 - 10 Nov 2022
Viewed by 825
Abstract
The editorial refers to the Special Issue “Pulmonary Arterial Hypertension: Old Drugs and New Treatment Strategies” [...] Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension: Old Drugs and New Treatment Strategies)

Research

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15 pages, 1219 KiB  
Article
Impact of Parenteral Prostanoids in Pulmonary Arterial Hypertension: The Relevance of Timing
by Silvia Papa, Gianmarco Scoccia, Giorgia Serino, Francesca Ileana Adamo, Jean Pierre Jabbour, Annalisa Caputo, Michela Boromei, Domenico Filomena, Domenico Laviola, Enrico Maggio, Giovanna Manzi, Alexandra Mihai, Tommaso Recchioni, Alexandra Sabusco, Livia Valeri, Sara Vinciullo, Carmine Dario Vizza and Roberto Badagliacca
J. Clin. Med. 2023, 12(21), 6840; https://doi.org/10.3390/jcm12216840 - 29 Oct 2023
Viewed by 1062
Abstract
Parenteral prostanoids are being recommended in pulmonary arterial hypertension (PAH) treatment, but the prognostic relevance of delayed treatment initiation is still debated. This study assessed the impact of the timing of prostacyclin treatment initiation on reducing PVR and achieving a low-risk profile in [...] Read more.
Parenteral prostanoids are being recommended in pulmonary arterial hypertension (PAH) treatment, but the prognostic relevance of delayed treatment initiation is still debated. This study assessed the impact of the timing of prostacyclin treatment initiation on reducing PVR and achieving a low-risk profile in PAH patients. The study enrolled 151 patients who started on parenteral prostanoids with different treatment strategies. All patients underwent right heart catheterization, clinical evaluation, and risk assessments at baseline and after 1-year follow-up. Patients with an upfront strategy including parenteral prostanoid plus one oral drug had −5.3 ± 6.2 WU (−50 ± 19%) reduction in PVR, patients with an upfront strategy including parenteral prostanoid plus double oral drug had −12.8 ± 5.9 WU (−68 ± 17%) reduction in PVR, while patients with an add-on strategy including parenteral prostanoid after oral drugs had −3.9 ± 3.5 WU (−23 ± 19%) reduction in PVR. An upfront strategy including parenteral prostanoids was independently associated with an increased likelihood of achieving the greater reduction of PVR compared with an add-on strategy. Additionally, the greater the severity of PH at the time of diagnosis, in terms of PVR and RV reverse remodeling, the higher the probability of treatment failure. An upfront strategy including a parenteral prostanoid is associated with the highest likelihood of achieving a low-risk profile and a greater reduction of PVR compared with parenteral prostanoid as an add-on to oral treatment. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension: Old Drugs and New Treatment Strategies)
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10 pages, 644 KiB  
Article
Left Heart Disease Phenotype in Elderly Patients with Pulmonary Arterial Hypertension: Insights from the Italian PATRIARCA Registry
by Matteo Toma, Roberta Miceli, Edoardo Bonsante, Davide Colombo, Marco Confalonieri, Andrea Garascia, Stefano Ghio, Mariangela Lattanzio, Carlo Maria Lombardi, Giuseppe Paciocco, Cristina Piccinino, Irene Rota, Caterina Santolamazza, Laura Scelsi, Piermario Scuri, Davide Stolfo, Antonella Vincenzi, Lorenzo Volpiano, Marco Vicenzi and Pietro Ameri
J. Clin. Med. 2022, 11(23), 7136; https://doi.org/10.3390/jcm11237136 - 30 Nov 2022
Cited by 5 | Viewed by 1532
Abstract
Pulmonary arterial hypertension (PAH) in the elderly is often associated with left heart disease (LHD), prompting concerns about the use of pulmonary vasodilators. The PATRIARCA registry enrolled ≥70 year-old PAH or chronic thromboembolic pulmonary hypertension (CTEPH) patients at 11 Italian centers from 1 [...] Read more.
Pulmonary arterial hypertension (PAH) in the elderly is often associated with left heart disease (LHD), prompting concerns about the use of pulmonary vasodilators. The PATRIARCA registry enrolled ≥70 year-old PAH or chronic thromboembolic pulmonary hypertension (CTEPH) patients at 11 Italian centers from 1 December 2019 through 15 September 2022. After excluding those with CTEPH, post-capillary PH at the diagnostic right heart catheterization (RHC), and/or incomplete data, 23 (33%) of a total of 69 subjects met the criteria proposed in the AMBITION trial to suspect LHD. Diabetes [9 (39%) vs. 6 (13%), p = 0.01] and chronic kidney disease [14 (61%) vs. 12 (26%), p = 0.003] were more common, and the last RHC pulmonary artery wedge pressure [14 ± 5 vs. 10 ± 3 mmHg, p < 0.001] was higher and pulmonary vascular resistance [5.56 ± 3.31 vs. 8.30 ± 4.80, p = 0.02] was lower in LHD than non-LHD patients. However, PAH therapy was similar, with 13 (57%) and 23 (50%) subjects, respectively, taking two oral drugs. PAH medication patterns remained comparable between LHD and non-LHD patients also when the former [37, 54%] were identified by atrial fibrillation and echocardiographic features of LHD, in addition to the AMBITION criteria. In this real-world snapshot, elderly PAH patients were treated with pulmonary vasodilators, including combinations, despite a remarkable prevalence of a LHD phenotype. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension: Old Drugs and New Treatment Strategies)
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14 pages, 12143 KiB  
Article
Risk Stratification of Patients with Pulmonary Arterial Hypertension: The Role of Echocardiography
by Valentina Mercurio, Hussein J. Hassan, Mario Naranjo, Alessandra Cuomo, Jeremy A. Mazurek, Paul R. Forfia, Aparna Balasubramanian, Catherine E. Simpson, Rachel L. Damico, Todd M. Kolb, Stephen C. Mathai, Steven Hsu, Monica Mukherjee and Paul M. Hassoun
J. Clin. Med. 2022, 11(14), 4034; https://doi.org/10.3390/jcm11144034 - 12 Jul 2022
Cited by 7 | Viewed by 1781
Abstract
Background: Given the morbidity and mortality associated with pulmonary arterial hypertension (PAH), risk stratification approaches that guide therapeutic management have been previously employed. However, most patients remain in the intermediate-risk category despite initial therapy. Herein, we sought to determine whether echocardiographic parameters could [...] Read more.
Background: Given the morbidity and mortality associated with pulmonary arterial hypertension (PAH), risk stratification approaches that guide therapeutic management have been previously employed. However, most patients remain in the intermediate-risk category despite initial therapy. Herein, we sought to determine whether echocardiographic parameters could improve the risk stratification of intermediate-risk patients. Methods: Prevalent PAH patients previously enrolled in observational studies at 3 pulmonary hypertension centers were included in this study. A validated PAH risk stratification approach was used to stratify patients into low-, intermediate-, and high-risk groups. Right ventricular echocardiographic parameters were used to further stratify intermediate-risk patients into intermediate-low- and intermediate-high-risk groups based on transplant-free survival. Results: From a total of 146 patients included in our study, 38 patients died over a median follow-up of 2.5 years. Patients with intermediate-/high-risk had worse echocardiographic parameters. Tricuspid annular plane systolic excursion (TAPSE) and the degree of tricuspid regurgitation (TR) were highly associated with survival (p < 0.01, p = 0.04, respectively) and were subsequently used to further stratify intermediate-risk patients. Among intermediate-risk patients, survival was worse for patients with TAPSE < 19 mm compared to those with TAPSE ≥ 19 mm (estimated one-year survival 74% vs. 96%, p < 0.01) and for patients with moderate/severe TR compared to those with no/trace/mild TR (estimated one-year survival 70% vs. 93%, p < 0.01). Furthermore, among intermediate-risk patients, those with both TAPSE < 19 mm and moderate/severe TR had an estimated one-year survival (56%) similar to that of high-risk patients (56%), and those with both TAPSE ≥ 19 mm and no/trace/mild TR had an estimated one-year survival (97%) similar to that of low-risk patients (95%). Conclusions: Echocardiography, a routinely performed, non-invasive imaging modality, plays a pivotal role in discriminating distinct survival phenotypes among prevalent intermediate-risk PAH patients using TAPSE and degree of TR. This can potentially help guide subsequent therapy. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension: Old Drugs and New Treatment Strategies)
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15 pages, 428 KiB  
Article
Exercise-Induced Pulmonary Hypertension Is Associated with High Cardiovascular Risk in Patients with HIV
by Rosalinda Madonna, Silvia Fabiani, Riccardo Morganti, Arianna Forniti, Filippo Biondi, Lorenzo Ridolfi, Riccardo Iapoce, Francesco Menichetti and Raffaele De Caterina
J. Clin. Med. 2022, 11(9), 2447; https://doi.org/10.3390/jcm11092447 - 27 Apr 2022
Cited by 3 | Viewed by 1593
Abstract
Background and Aim: Pulmonary hypertension (PH) at rest can be preceded by the onset of exercise-induced PH (ExPH). We investigated its association with the cardiovascular (CV) risk score in patients with human immunodeficiency virus (HIV). Methods: In 46 consecutive patients with HIV with [...] Read more.
Background and Aim: Pulmonary hypertension (PH) at rest can be preceded by the onset of exercise-induced PH (ExPH). We investigated its association with the cardiovascular (CV) risk score in patients with human immunodeficiency virus (HIV). Methods: In 46 consecutive patients with HIV with low (n = 43) or intermediate (n = 3) probability of resting PH, we evaluated the CV risk score based on prognostic determinants of CV risk. Diagnosis of ExPH was made by cardiopulmonary exercise test (CPET) and exercise stress echocardiogram (ESE). Results: Twenty-eight % (n = 13) of the enrolled patients had ExPH at both CPET and ESE, with good agreement between the two methods (Cohen’s kappa = 0.678). ExPH correlated directly with a higher CV score (p < 0.001). Patients with a higher CV score also had lower CD4+ T-cell counts (p = 0.001), a faster progression to acquired immunodeficiency syndrome (p < 0.001), a poor immunological response to antiretroviral therapy (p = 0.035), higher pulmonary vascular resistance (p = 0.003) and a higher right atrial area (p = 0.006). Conclusions: Isolated ExPH is associated with a high CV risk score in patients with HIV. Assessment of ExPH may better stratify CV risk in patients with HIV. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension: Old Drugs and New Treatment Strategies)
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Review

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21 pages, 993 KiB  
Review
The Current Role of Cardiopulmonary Exercise Test in the Diagnosis and Management of Pulmonary Hypertension
by Beatrice Pezzuto and Piergiuseppe Agostoni
J. Clin. Med. 2023, 12(17), 5465; https://doi.org/10.3390/jcm12175465 - 23 Aug 2023
Cited by 1 | Viewed by 1081
Abstract
Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis if left untreated. Despite remarkable achievements in understanding disease pathophysiology, specific treatments, and therapeutic strategies, we are still far from a definitive cure for the disease, and numerous evidences have underlined [...] Read more.
Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis if left untreated. Despite remarkable achievements in understanding disease pathophysiology, specific treatments, and therapeutic strategies, we are still far from a definitive cure for the disease, and numerous evidences have underlined the importance of early diagnosis and treatment to improve the prognosis. Cardiopulmonary exercise testing (CPET) is the gold standard for assessing functional capacity and evaluating the pathophysiological mechanisms underlying exercise limitation. As effort dyspnea is the earliest and one of the main clinical manifestations of PAH, CPET has been shown to provide valid support in early detection, differential diagnosis, and prognostic stratification of PAH patients, being a useful tool in both the first approach to patients and follow-up. The purpose of this review is to present the current applications of CPET in pulmonary hypertension and to propose possible future utilization to be further investigated. Full article
(This article belongs to the Special Issue Pulmonary Arterial Hypertension: Old Drugs and New Treatment Strategies)
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