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Atrial arrhythmias (AA) are common in patients with pulmonary hypertension (PH) and contribute to morbidity and mortality. Given the growing PH population, understanding the pathophysiology, clinical impact, and management of AA in PH is important. AA occurs in PH with a 5-year incidence of 10% to 25%. AA confers a higher morbidity and mortality, and restoration of normal sinus rhythm improves survival and functionality. AA is thought to develop because of structural alterations of the right atrium caused by changes to the right ventricle (RV) due to elevated pulmonary artery pressures. AA can subsequently worsen RV function. Current guidelines do not provide comprehensive recommendations for the management of AA in PH. Robust evidence to favor a specific treatment approach is lacking. Although the role of medical rate or rhythm control, and the use of cardioversion and ablation, can be inferred from other populations, evidence is lacking in the PH population. Much remains to be determined regarding the optimal management strategy. We present here our institutional approach and discuss areas for future research. This review highlights the epidemiology and pathophysiology of AA in patients with PH, describes the relationship between AA and RV dysfunction, and discusses current management practices. We outline our institutional approach and offer directions for future investigation. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a frequent complication of interstitial lung disease (ILD). Although PH has mostly been described in idiopathic pulmonary fibrosis, it can manifest in association with many other forms of ILD. Associated pathogenetic mechanisms are complex and incompletely understood but there is evidence of disruption of molecular and genetic pathways, with panvascular histopathologic changes, multiple pathophysiologic sequelae, and profound clinical ramifications. While there are some recognized clinical phenotypes such as combined pulmonary fibrosis and emphysema and some possible phenotypes such as connective tissue disease associated with ILD and PH, the identification of further phenotypes of PH in ILD has thus far proven elusive. This statement reviews the current evidence on the pathogenesis, recognized patterns, and useful diagnostic tools to detect phenotypes of PH in ILD. Distinct phenotypes warrant recognition if they are characterized through either a distinct presentation, clinical course, or treatment response. Furthermore, we propose a set of recommendations for future studies that might enable the recognition of new phenotypes. [ABSTRACT FROM AUTHOR]

Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PHdiseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis. Glutaminolysis, an anaplerotic pathway, replenished aspartate for anabolic biosynthesis, which was critical for sustaining proliferation and migration within stiff ECM. In vitro, GLS1 inhibition blocked aspartate production and reprogrammed cellular proliferation pathways, while application of aspartate restored proliferation. In the monocrotaline rat model of PH, pharmacologic modulation of pulmonary vascular stiffness and YAP- dependent mechanotransduction altered glutaminolysis, pulmonary vascular proliferation, and manifestations of PH. Additionally, pharmacologic targeting of GLS1 in this model ameliorated disease progression. Notably, evaluation of simian immunodeficiency virus-infected nonhuman primates and HIV-infected subjects revealed a correlation between YAP/TAZ-GLS activation and PH. These results indicate that ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis and anaplerosis, and thereby link mechanical stimuli to dysregulated vascular metabolism. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in PH., Introduction Pulmonary hypertension (PH) and its particularly severe subtype pulmonary arterial hypertension (PAH) are poorly understood vascular diseases, characterized by pro-proliferative cellular phenotypes and adverse pulmonary vascular remodeling. Alterations of [...]

Background: Emergent endotracheal intubations (ETI) in pulmonary hypertension (PH) patients are associated with increased mortality. Post-intubation interventions that could increase survivability in this population have not been explored. We evaluate early clinical characteristics and complications following emergent endotracheal intubation and seek predictors of adverse outcomes during this post-intubation period. Methods: Retrospective cohort analysis of adult patients with groups 1 and 3 PH who underwent emergent intubation between 2005-2021 in medical and liver transplant ICUs at a tertiary medical center. PH patients were compared to non-PH patients, matched by Charlson Comorbidity Index. Primary outcomes were 24-h post-intubation and inpatient mortalities. Various 24-h post-intubation secondary outcomes were compared between PH and control cohorts. Results: We identified 48 PH and 110 non-PH patients. Pulmonary hypertension was not associated with increased 24-h mortality (OR 1.32, 95%CI 0.35-4.94, P =.18), but was associated with inpatient mortality (OR 4.03, 95%CI 1.29-12.5, P =.016) after intubation. Within 24 h post-intubation, PH patients experienced more frequent acute kidney injury (43.5% vs. 19.8%, P =.006) and required higher norepinephrine dosing equivalents (6.90 [0.13-10.6] mcg/kg/min, vs. 0.20 [0.10-2.03] mcg/kg/min, P =.037). Additionally, the median P/F ratio (PaO2/FiO2) was lower in PH patients (96.3 [58.9-201] vs. 233 [146-346] in non-PH, P =.001). Finally, a post-intubation increase in PaCO2 was associated with mortality in the PH cohort (post-intubation change in PaCO2 +5.14 ± 16.1 in non-survivors vs. −18.7 ± 28.0 in survivors, P =.007). Conclusions: Pulmonary hypertension was associated with worse outcomes after emergent endotracheal intubation than similar patients without PH. More importantly, our data suggest that the first 24 hours following intubation in the PH group represent a particularly vulnerable period that may determine long-term outcomes. Early post-intubation interventions may be key to improving survival in this population. [ABSTRACT FROM AUTHOR]

Development of the vascular disease pulmonary hypertension (PH) involves disparate molecular pathways that span multiple cell types. MicroRNAs (miRNAs) may coordinately regulate PH progression, but the integrative functions of miRNAs in this process have been challenging to define with conventional approaches. Here, analysis of the molecular network architecture specific to PH predicted that the miR-130/301 family is a master regulator of cellular proliferation in PH via regulation of subordinate miRNA pathways with unexpected connections to one another. In validation of this model, diseased pulmonary vessels and plasma from mammalian models and human PH subjects exhibited upregulation of miR-130/301 expression. Evaluation of pulmonary arterial endothelial cells and smooth muscle cells revealed that miR130/301 targeted PPARγ with distinct consequences. In endothelial cells, miR-130/301 modulated apelin-miR-424/503FGF2 signaling, while in smooth muscle cells, miR-130/301 modulated STAT3-miR-204 signaling to promote PH-associated phenotypes. In murine models, induction of miR-130/301 promoted pathogenic PH-associated effects, while miR-130/301 inhibition prevented PH pathogenesis. Together, these results provide insight into the systems-level regulation of miRNAdisease gene networks in PH with broad implications for miRNA-based therapeutics in this disease. Furthermore, these findings provide critical validation for the evolving application of network theory to the discovery of the miRNA-based origins of PH and other diseases., Introduction Pulmonary hypertension (PH) is an enigmatic vascular disease with poorly defined molecular origins. It is driven by various disparate triggers (hypoxia and inflammation, among others); it is marked by [...]

Venovenous (VV) extracorporeal membrane oxygenation (ECMO) has been used as a bridge to lung transplantation with acceptable outcomes. We hypothesized that venoarterial (VA) ECMO, as part of a multidisciplinary ECMO program, yields similar outcomes as VV ECMO as a bridge in lung transplantation. Records of all patients who had undergone ECMO with the intention to bridge to lung transplantation at University of California, Los Angeles, from January 1, 2012, to March 31, 2020, were reviewed. Baseline characteristics, in-hospital outcomes, long-term survival, and freedom from bronchiolitis obliterans syndrome were assessed. During this interval, 58 patients were placed on ECMO with the intention to bridge to lung transplantation: 27 on VV ECMO, and 31 on VA ECMO, with a median duration of 7 and 17 days of support, respectively (P =.01). Successful bridge to lung transplantation occurred in 21 VV patients (78%) and in 26 VA patients (84%). Incidence of primary graft dysfunction III at 72 hours in the VV and the VA cohorts was 0% and 4%, respectively (P =.99). In-hospital and 90-day survival of the VV and VA groups was 100% and 96%, respectively (P =.99). Survival of the 2 groups at 3 years was not significantly different from a contemporary cohort of lung transplant recipients not bridged with ECMO. VA and VV ECMO can both be used as a bridge to lung transplantation with high success, with short and medium-term survival similar to non-bridged lung transplant recipients. Both modes should be considered effective at bridging select candidates to lung transplantation. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) has been linked to worse outcomes in chronic lung diseases. The presence of PH in the setting of underlying Interstitial Lung Disease (ILD) is strongly associated with decreased exercise and functional capacity, an increased risk of hospitalizations and death. Examining the scope of this issue and its impact on patients is the first step in trying to define a roadmap to facilitate and encourage future research in this area. The aim of our working group is to strengthen the communities understanding of PH due to lung diseases and to improve the care and quality of life of affected patients. This introductory statement provides a broad overview and lays the foundation for further in‐depth papers on specific topics pertaining to PH‐ILD. [ABSTRACT FROM AUTHOR]

The follow-up of patients with acute pulmonary embolism is an essential component of their comprehensive care. This manuscript will discuss the critical components involved in the outpatient follow-up of pulmonary embolism, including the development of post hospitalization follow-up clinics, assessment of functional capacity and residual right ventricular function, anticoagulation, recurrence risk of venous thromboembolism, and retrieval of inferior vena cava filters. In addition to these listed topics, the epidemiology of chronic thromboembolic pulmonary hypertension will be discussed, including the spectrum of postpulmonary embolism syndrome (PPES), risk factors for the development of chronic thromboembolic pulmonary hypertension, and the incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. [ABSTRACT FROM AUTHOR]