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Open research questions in Pulmonary Hypertension Research and Treatments

642 gap statements mined from Pulmonary Hypertension Research and Treatments papers in our 7.9M-paper local library, which holds 2,635 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The small and heterogeneous cohort of the study may limit the generalizability of the results. The lack of standardized procedures, such as the use of oxygen and inhaled nitric oxide, may affect the accuracy of the findings. The exclusion of certain patient groups, such as those with Eisenmenger syndrome, in previous studies may limit the applicability of the results to the broader pediatric PAH population.

    Sotatercept in Pediatric Pulmonary Hypertension: Promising Hemodynamic Findings, but Are We Extrapolating Too Far? · 2026 · DOI

  • The authors note that the lack of standardized procedures and the small sample size of the study may limit the generalizability of the results. The paper highlights the need for further research to fully understand the effects of sotatercept in pediatric pulmonary hypertension.

    Sotatercept in Pediatric Pulmonary Hypertension: Promising Hemodynamic Findings, but Are We Extrapolating Too Far? · 2026 · DOI

  • The effects of SGLT2 inhibitors on right ventricular function in acute pulmonary embolism remain largely unexplored. There is a lack of studies investigating the association between pre-existing SGLT2 inhibitor use and RV function and biomarker profile at presentation among patients with PE.

    Association between chronic sodium-glucose cotransporter 2 inhibitors use and right ventricular function in hemodynamically stable patients with acute pulmonary embolism · 2026 · DOI

  • Prior PAH bibliometric studies have not treated the stem-cell-to-cell-free arc as a dedicated research front. Manufacturing standardization, targeting efficiency, and large-scale clinical evidence remain unresolved. No phase III trial has been completed for any stem cell- or EV-based product.

    Stem cells, extracellular vesicles, and cell-free strategies in pulmonary arterial hypertension: a bibliometric study, 2006–2026 · 2026 · DOI

  • The accurate measurement of PCWP, especially in patients with HFpEF or atrial fibrillation, can be technically challenging. The limitations of right heart catheterization, including its invasiveness and procedural risks. The need for a comprehensive understanding of the molecular pathways that lead to irreversibility of PH in LHD.

    Hemodynamic Definitions, Phenotypes, Pathophysiology, and Evaluation of Pulmonary Hypertension Related to Left Heart Disease · 2025 · DOI

  • There is a lack of comprehensive evidence on exercise training for patients with CTEPH. CTEPH cases represent only 10-30% of the total research cases on pulmonary hypertension.

    The Efficacy and Safety of Outpatient Exercise Training for Patients with Chronic Thromboembolic Pulmonary Hypertension After Balloon Pulmonary Angioplasty · 2025 · DOI

  • The efficacy and safety of DOACs in CTEPH are unclear. There is a lack of robust randomized trials in CTEPH. There is limited data on the use of DOACs in high-risk subgroups, such as antiphospholipid syndrome and severe renal impairment.

    Oral Anticoagulants in Chronic Thromboembolic Pulmonary Hypertension: Tradition or Innovation? · 2025 · DOI

  • Limited treatment options for PH-COPD patients. Unclear efficacy of inhaled treprostinil in PH-COPD. Need for precision phenotyping in PH-COPD treatment.

    Right Ventricular Phenotyping Can Lead to Pulmonary Vascular Therapy Response in Those with Pulmonary Hypertension with COPD: A Single-Center Cohort Study · 2025 · DOI

  • The role of Urolithin A in mitigating hypoxia-induced pulmonary hypertension was unknown. The underlying mechanisms of Urolithin A in inhibiting PASMC pyroptosis were not fully understood.

    Urolithin A Protects against Hypoxia-Induced Pulmonary Hypertension by Inhibiting Pulmonary Arterial Smooth Muscle Cell Pyroptosis via AMPK/NF-κB/NLRP3 Signaling · 2024 · DOI

  • Chronic asthma can be associated with secondary pulmonary vascular dysfunction, however, the detailed functional profiling of the asthmatic pulmonary artery remains understudied.

    Chronic Mixed-Allergen Exposure Induces Pulmonary Arterial Remodeling and Vascular Dysfunction in Mice · 2026 · DOI

  • Pulmonary arterial hypertension (PAH) is a lethal vascular disorder characterized by irreversible remodeling of the pulmonary arteries, but the systematic role of the integrated stress response (ISR)-related genes (ISR-RGs) in its pathogenesis remains unexplored.

    Bulk and single-cell transcriptomics for identification of potential diagnostic biomarkers associated with pulmonary arterial hypertension and integrated stress response and experimental validation · 2026 · DOI

  • In patients presenting with severe PAH, therapeutic decision-making remains challenging because precise and individualized assessment criteria are lacking.

    Preliminary study of individualized therapy for ventricular septal defect with severe pulmonary arterial hypertension · 2026 · DOI

  • Further investigation into the relationship between gut microbial Lactobacillus, circulating metabolites, disease severity, and clinical outcomes in pulmonary arterial hypertension may be warranted.

    Lactobacillus Is Associated With Disease in Pulmonary Arterial Hypertension: A Prospective Cohort Study · 2026 · DOI

  • The liver's contribution to pulmonary arterial hypertension (PAH) pathogenesis remains unclear.

    Exploring the Lung–Liver Axis in Pulmonary Arterial Hypertension · 2026 · DOI

  • Methamphetamine (MA) use is a recognized risk factor for drug-associated pulmonary arterial hypertension (PAH), yet mechanisms driving methamphetamine-associated PAH (MA-PAH) remain unclear due to the lack of reproducible animal models demonstrating hemodynamic changes.

    Exposure Pattern Determines Methamphetamine‐Induced Right Ventricular Dysfunction and Vascular Remodeling · 2026 · DOI

  • Limited availability of RV-focused 4ACH views for RV strain analysis. Suboptimal image quality and high exclusion rate due to poor echocardiographic quality.

    Right Ventricular Strain in Healthy Children: Insights from Speckle-Tracking Echocardiography · 2025 · DOI

  • Although mtASIC1a has not been described in vascular cells, its role in PASMCs may be relevant to mitochondrial dysfunction and apoptosis resistance in PH.

    Mitochondrial acid-sensing ion channel 1a deficiency induces mitochondrial dysfunction in pulmonary arterial smooth muscle cells · 2026 · DOI

  • Precision-oriented, mechanism-driven investigations are needed, - Engineering toolbox incorporating surface functionalization, pharmacological preconditioning, and genetic cargo modulation for targeted therapy, - Clinical translation of stem cell- and EV-based…

    Stem cells, extracellular vesicles, and cell-free strategies in pulmonary arterial hypertension: a bibliometric study, 2006–2026 · 2026 · DOI

  • The availability of RHC is often limited to specialized centers, - RHC is also invasive and associated with procedural risks, particularly in elderly or frail patients, - The accurate measurement of PCWP can be technically challenging and subject to inter-operator…

    Hemodynamic Definitions, Phenotypes, Pathophysiology, and Evaluation of Pulmonary Hypertension Related to Left Heart Disease · 2025 · DOI

  • The high exclusion rate due to missing RV-focused A4CH views or suboptimal image quality, - The small sample size limited the ability to develop Z-score equations, - The low coefficients of determination (R 2) limited the reliability of the results, - The study was limited to GE Healthcare equipment…

    Right Ventricular Strain in Healthy Children: Insights from Speckle-Tracking Echocardiography · 2025 · DOI

  • Limited research on bradycardias in PH patients - Unclear prevalence and clinical relevance…

    Bradycardias in Patients with Pulmonary Hypertension—Prevalence, Pathophysiology and Clinical Relevance · 2025 · DOI

  • Further studies with larger sample sizes are needed, - Randomized controlled trials are needed to confirm the results, - Studies on the long-term effects of exercise training on patients with CTEPH…

    The Efficacy and Safety of Outpatient Exercise Training for Patients with Chronic Thromboembolic Pulmonary Hypertension After Balloon Pulmonary Angioplasty · 2025 · DOI

  • Limited large-scale RCTs in CTEPH - Higher VTE recurrence in some registries - Not suitable for APLS or severe CKD (GFR <15) - Most studies are observational…

    Oral Anticoagulants in Chronic Thromboembolic Pulmonary Hypertension: Tradition or Innovation? · 2025 · DOI

  • The study was conducted in a rat model, - The sample size was limited to 8 rats per…

    Transection of the cervical sympathetic trunk ameliorates pulmonary arterial hypertension by reprogramming transcription factor networks and alternative splicing in rat model · 2026 · DOI

  • Our observations support a lung-liver axis in PAH even in the absence of liver disease, warranting further study.

    Exploring the Lung–Liver Axis in Pulmonary Arterial Hypertension · 2026 · DOI

Most-cited papers in Pulmonary Hypertension Research and Treatments

Most recent work

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Open questions raised by papers listed on this page include: (1) The lack of standardized procedures, such as the use of oxygen and inhaled nitric oxide, may affect the accuracy of the findings (“Sotatercept in Pediatric Pulmonary Hypertension: Promising Hemodynamic…”, 2026); (2) The effects of SGLT2 inhibitors on right ventricular function in acute pulmonary embolism remain largely unexplored (“Association between chronic sodium-glucose cotransporter 2 inhibitors use and…”, 2026); (3) Manufacturing standardization, targeting efficiency, and large-scale clinical evidence remain unresolved (“Stem cells, extracellular vesicles, and cell-free strategies in pulmonary…”, 2026); (4) Chronic asthma can be associated with secondary pulmonary vascular dysfunction, however, the detailed functional profiling of the asthmatic pulmonary artery remains understudied (“Chronic Mixed-Allergen Exposure Induces Pulmonary Arterial Remodeling and…”, 2026); (5) In patients presenting with severe PAH, therapeutic decision-making remains challenging because precise and individualized assessment criteria are lacking (“Preliminary study of individualized therapy for ventricular septal defect with…”, 2026). 642 gap statements have been mined from Pulmonary Hypertension Research and Treatments papers in our 7.9M-paper local library, which holds 2,635 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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