What are the 4 groups of pulmonary hypertension?
Abstract. Pulmonary hypertension continues to be a life-threatening illness with debilitating physical and emotional consequences affecting around 1% of global population. The progression of this devastating disease is characterized by increase in pulmonary vascular resistance resulting in elevated pulmonary pressure, eventually leading to ...
What are the European Society of Cardiology/European Respiratory Society guidelines for pulmonary hypertension?
May 01, 2018 · Better understanding of pathophysiology has led to substantial improvements in terms of availability of treatment options. The purpose of this review is to summarize the currently available treatment options along with pertinent trials and possible future therapies of pulmonary hypertension group II-V.
What is the pathophysiology of Group 2 pulmonary hypertension (PH)?
Mar 21, 2022 · Three drug classes are FDA-approved for chronic treatment of WHO Group 1 PH (pulmonary arterial hypertension), whereas no drugs have been approved for Groups 2–5. Current treatments Prostacyclin analogs are the only drug class that have demonstrated a mortality benefit in pulmonary arterial hypertension, but are plagued by a poor side-effect ...
What are the guidelines for diagnosis and treatment of pulmonary hypertension?
Mar 01, 2009 · Past decades have witnessed an increasing interest in the field of pulmonary arterial hypertension (PAH). The large number of publications related to PAH reflects this interest. As a result, in contrast to 15 yrs ago, there are now at least seven different drugs as specific therapy targeting the pulmonary circulation that are approved for use in the USA and European …
What is CTEPH in pulmonary hypertension?
Chronic thromboembolic pulmonary hypertension (CTEPH) occurs due to chronic nonresolving thromboembolic occlusion of pulmonary vasculature and is defined as mPAP > 25 mm Hg lasting for more than 6 months following treatment with anticoagulation.39 In a study, its incidence and prevalence are found to be 0.9 cases and 3.2 cases per million per year, respectively. 40 It is estimated that almost around 2500 new cases of CTEPH are diagnosed yearly in the United States.41 The pathophysiology remains complex and it is still debatable why some patients tend to develop CTEPH following acute PE while others do not.42 Some thrombophilic factors such as increased level of factor VIII 43 antiphospholipid antibodies 42 are statistically related to increased incidence of CTEPH. One hypothesis suggests that blockage of pulmonary vasculature is followed by secondary vasculopathy resulting in increased localized inflammation, endothelial dysfunction, and disruption of angiogenesis resulting in PH.42 Even with advances in diagnostic modalities such as computed tomography and magnetic resonance imaging, Ventilation-Perfusion (VQ) scan remains the screening test for the diagnosis of CTEPH.14
What is balloon pulmonary artery angioplasty?
Balloon pulmonary artery angioplasty (BPA), is an alternative option for patients who are not amenable for PTE and with recurrent disease following PTE. In 2001, Feinstein et al reported improvement in 6MWD and mPAP in 18 patients with inoperable CTEPH following BPA,54 but 11 patients developed reperfusion injury. In an another study with 68 patients with inoperable CTEPH, BPA was performed in a staged approach, with an average of 4 procedure in each patient in order to reduce the risk of reperfusion injury.55 The study showed improvement in WHO-FC and mPAP following procedures; however, around 41 (60%) patients suffered reperfusion injury. As BPA requires multiple procedures, radiation exposure, and risk of reperfusion injury, it should only be performed in an expertise experienced center. Additional studies are needed to better delineate the role of BPA in CTEPH patients and reduce the risk of reperfusion injuries.
What is the PH of a patient?
PH is defined as mean pulmonary artery pressure (mPAP) of 25 mm Hg or greater at rest, requiring confirmation of the diagnosis with right heart catheterization (RHC).1 With the upper limit of mPAP of up to 20 mm Hg, 2 the data on classification and management of patients for mPAP between 21 and 24 mm Hg remain unclear. The 6-minute walking distance (6MWD) is considered as an independent determinant of mortality in Pulmonary arterial Hypertension (PAH). 3
What is Group 3 PH?
Group 3 PH is attributed to chronic lung diseases such as chronic obstructive airway disease (COPD) or hypoxia. Although severe PH is uncommon in the setting of COPD, however, its prevalence is high in combined pulmonary fibrosis and emphysema syndrome.28 The treatment of PH secondary to lung disease or hypoxia is focused on the treatment of underlying disease such as COPD, Idiopathic pulmonary fibrosis (IPF), based on current guidelines.29 Long-term oxygen treatment has shown to improve life expectancy in COPD patients with the partial pressure of oxygen <60 mm Hg. 29 Systemic vasodilators approved for PAH may worsen gas exchange in patients with lung disease by interfering with hypoxic vasoconstriction and diverting pulmonary blood flow to less affected part of the lung. However, inhaled vasodilators such as iloprost,30 nitric oxide 31 with their selective accumulation in better-ventilated areas of the lung, may serve as life-saving therapy in these patients and warrant further RCTs comparing their effect on hemodynamic variables. Endothelin Receptor Antagonists (ERAs) such as bosentan is found to be well tolerated in IPF patients but failed to delay IPF worsening or death.32 However, it will be interesting to see the results of bosentan trial in IPF-associated PH patients which is currently under phase 4 (B-PHIT trial, NCT00637065) trial. Unfavorable results were also seen with ambrisentan resulting in early termination of study as a result of increased rate of disease progression.33 A controlled trial of sildenafil on advanced IPF patients failed to improve the primary outcome (6MWD of 20% or more); however, secondary outcomes such as changes in oxygenation and the degree of dyspnea were achieved.34 Additional studies of sildenafil in IPF patients were currently being investigated (NCT00625079, phase 4). Another pilot trial assessing the safety and tolerability of riociguat in IPF-associated PH patients seemed to improve cardiac output and pulmonary vascular resistance (PVR) but mPAP remained unchanged from baseline necessitating further studies to evaluate the role of this drug in these patients.
Is pulmonary hypertension a life threatening disease?
Pulmonary hypertension continues to be a life-threatening illness with debilitating physical and emotional consequences affecting around 1% of global population. The progression of this devastating disease is characterized by increase in pulmonary vascular resistance resulting in elevated pulmonary pressure, eventually leading to right heart failure and death. Better understanding of pathophysiology has led to substantial improvements in terms of availability of treatment options. The purpose of this review is to summarize the currently available treatment options along with pertinent trials and possible future therapies of pulmonary hypertension group II-V.
What is the GRIPHON study?
The GRIPHON study was a multicenter, double-blind, randomized, parallel-group, placebo-controlled, event-driven, phase 3 study. The steering committee, in collaboration with the sponsor (Actelion Pharmaceuticals), designed the trial and oversaw its conduct and the analyses of the data. The study protocol, which is available with the full text of this article at NEJM.org, was approved by the review board or ethics committee at each participating site. The study was monitored by an independent data and safety monitoring committee (see the Supplementary Appendix, available at NEJM.org). The collection, management, and analysis of the data were performed by the sponsor according to a prespecified statistical analysis plan (available with the protocol) that was reviewed by two independent academic statisticians. All drafts of the manuscript were written by the first author and the last two (senior) authors, as well as the three authors affiliated with the sponsor, and were reviewed and edited by all the authors. The steering committee members, all of whom are authors of this article, and the three authors affiliated with Actelion Pharmaceuticals were involved in the decision to submit the manuscript for publication. All the authors had access to the data and vouch for the accuracy and completeness of the analyses and for the fidelity of this report to the study protocol.
What is the primary end point in a time-to-event analysis?
The primary end point in a time-to-event analysis was a composite of death or a complication related to pulmonary arterial hypertension, whichever occurred first, up to the end of the treatment period. Complications related to pulmonary arterial hypertension were disease progression or worsening of pulmonary arterial hypertension that resulted in hospitalization, initiation of parenteral prostanoid therapy or long-term oxygen therapy, or the need for lung transplantation or balloon atrial septostomy as judged by the physician. (Placement on a transplant waiting list represented an acute measure, as confirmed by the critical-event committee, and an actual lung transplantation would also meet this criterion.) Disease progression was defined as a decrease from baseline of at least 15% in the 6-minute walk distance (confirmed by means of a second test on a different day) accompanied by a worsening in WHO functional class (for the patients with WHO functional class II or III at baseline) or the need for additional treatment of pulmonary arterial hypertension (for the patients with WHO functional class III or IV at baseline). An independent critical-event committee whose members were unaware of the study-group assignments adjudicated all events up to the end of the study, including each death, to determine whether it was due to pulmonary arterial hypertension.