New Perspectives on Pulmonary Hypertension (PH)

The activation of pulmonary adventitial fibroblasts (PAFs) is one of the key components of pulmonary arterial remodelling in pulmonary arterial hypertension (PAH). Emerging evidence indicates that lncRNAs may play fibrotic roles in a range of diseases. In this present study, we identified a novel lncRNA, LNC_000113, in pulmonary adventitial fibroblasts (PAFs) and characterised its role in the Galectin-3-induced activation of PAFs in rats. Galectin-3 led to elevated expression of lncRNA LNC_000113 in PAFs. The expression of this lncRNA was primarily PAF enriched. A progressive increase in lncRNA LNC_000113 expression was observed in rats with monocrotaline (MCT)-induced PAH rats. Knockdown of lncRNA LNC_000113 cancelled the Galectin-3′s fibroproliferative effect on PAFs and prevented the transition of fibroblasts to myofibroblasts. The loss-of-function study demonstrated that lncRNA LNC_000113 activated PAFs through the PTEN/Akt/FoxO1 pathway. These results propose lncRNA LNC_000113 drives the activation of PAFs and promotes fibroblast phenotypic alterations. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5–2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary artery obstruction, heart failure, and poor prognosis. Little is known about involvement of autonomic nervous system (ANS) in the mechanisms of CTEPH. This study was aimed at evaluation of the effect of vagal and sympathetic denervation, as well as stimulation of the parasympathetic nervous system, on the outcomes of CTEPH in rats. CTEPH was induced by multiple intravenous injections of alginate microspheres. Sympathetic and vagal denervation was performed using unilateral surgical ablation of the stellate ganglion and vagotomy, respectively. Stimulation of the parasympathetic nervous system was carried out by administering pyridostigmine. The effect of neuromodulatory effects was assessed in terms of hemodynamics, histology, and gene expression. The results demonstrated the key role of ANS in the development of CTEPH. Sympathetic denervation as well as parasympathetic stimulation resulted in attenuated pulmonary vascular remodeling. These salutary changes were associated with altered MMP2 and TIMP1 expression in the lung and decreased FGFb level in the blood. Unilateral vagotomy had no effect on physiological and morphological outcomes of the study. The data obtained contribute to the identification of new therapeutic targets for CTEPH treatment. Full article

(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m² (n = 81), and absence as a PA/BSA < 16.6 mm/m² (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m² showed significantly higher levels of BNP (p = <0.001), GDF-15 (p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m², cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585–0.857; p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590–0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA < 16.6 mm/m² and patients with PA/BSA ≥ 16.6 mm/m² was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS. Full article

Pulmonary hypertension (PH) refers to a pathologic elevation of the mean pulmonary artery pressure (mPAP) and is associated with increased morbidity and mortality in a wide range of medical conditions. These conditions are classified according to similarities in pathophysiology and management in addition to their invasive hemodynamic profiles. The 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension present the newest clinical classification system and includes significant updates to the hemodynamic definitions. Pulmonary hypertension is now hemodynamically defined as an mPAP > 20 mmHg, reduced from the previous threshold of ≥25 mmHg, due to important insights from both normative and prognostic data. Pulmonary vascular resistance has been extended into the definition of pre-capillary pulmonary hypertension, with an updated threshold of >2 Wood Units (WU), to help differentiate pulmonary vascular disease from other causes of increased mPAP. Exercise pulmonary hypertension has been reintroduced into the hemodynamic definitions and is defined by an mPAP/cardiac output slope of >3 mmHg/L/min between rest and exercise. While these new hemodynamic thresholds will have a significant impact on the diagnosis of pulmonary hypertension, no evidence-based treatments are available for patients with mPAP between 21–24 mmHg and/or PVR between 2–3 WU or with exercise PH. This review highlights the evidence underlying these major changes and their implications on the diagnosis and management of patients with pulmonary hypertension. Full article

Pulmonary hypertension is a well-established independent risk factor for perioperative complications after elective non-cardiac surgery. Patients undergoing cardiac surgery are routinely evaluated for the presence of pulmonary hypertension in the preoperative period. Better monitoring in the postoperative critical care setting leads to more efficient management of potential complications. Data among patients with pulmonary hypertension undergoing elective non-cardiac surgery are scant. Moreover, the condition may be unidentified at the time of surgery. Also, monitoring after non-cardiac surgery can be very limited in the PACU setting, as opposed to the critical care setting. All these factors can result in a higher postoperative complication rate and poor outcomes. Full article

Pulmonary hypertension (PH) was once a devastating and fatal disease entity, the outlook of which has been significantly improved by the continued progress of medical treatment algorithms. However, some patients still ultimately fail to achieve an adequate clinical response despite receiving maximal medical treatment. Historically, lung transplantation (LTx) has been the only effective therapeutic option that could lead to satisfactory outcomes and save these advanced patients’ lives. However, patients with PH tend to have the highest mortality rates on the transplant waiting list; especially after comprehensive medical treatment, they continue to deteriorate very rapidly, eventually missing optimal transplantation windows. Balancing optimized medical treatment with the appropriate timing of referral and listing has been highly controversial in LTx for patients with PH. The 2021 consensus document for the selection of lung transplant candidates from the International Society for Heart and Lung Transplantation (ISHLT) updated the specific recommendations for the LTx referral and listing time for patients with PH based on objective risk stratification. Herein, we review the evolving PH-related concepts and highlight the optimization of LTx referral and listing for patients with PH, as well as their management on the waiting list. Full article

The management of chronic thromboembolic pulmonary hypertension has significantly changed over the last decade with the availability of both specific therapies and interventional treatments. In parallel, implantable pumps for intravenous administration of treprostinil have broadened the spectrum of continuous prostanoid infusion. We evaluated the course of 17 consecutive patients with inoperable chronic thromboembolic pulmonary hypertension treated with treprostinil by means of an implantable infusion pump between 2011 and 2023 at our center. Complications associated with the infusion system were rare, leading to 0.4 unplanned surgical interventions during 17,160 patient days. No additional safety signals were detected, and clinical benefits achieved with subcutaneous treprostinil before pump implantation could be maintained in all patients. No catheter-related infections or thromboembolic events were observed. Implantable infusion pumps offer an attractive alternative to subcutaneous treprostinil for patients intolerant to the subcutaneous route, including those with chronic thromboembolic pulmonary hypertension. Full article