RESEARCH

Scientific Sessions

Stay informed about the latest pulmonary hypertension research with summaries from our annual National Pulmonary Hypertension Scientific Sessions

The National Pulmonary Hypertension Scientific Sessions convenes pulmonary hypertension experts and other academic researchers to share the latest in PH research from across Canada and beyond.

In 2027, the National PH Scientific Sessions will be held in Halifax on September 24, as part of the 2027 Pulmonary Hypertension Community Conference. A virtual option will be available. Specialists and non-specialists are welcome! Registration will open in the spring of 2027.

Sharing good quality research news with the pulmonary hypertension community is a top priority for PHA Canada. Here are a few summaries from previous sessions. See our Research News page for more research-related updates.

2026 Scientific Sessions

Endothelial senescence as a therapeutic target in PAH

Presented by Dr. Duncan Stewart, Ottawa Heart Institute

Background: Pulmonary arterial hypertension (PAH) has many different things going on at different times. The initial triggering injury initiates a repair response. However, in patients who develop PAH, the repair is incomplete and is overwhelmed by persistent vascular injury, which eventually leads to maladaptive remodelling and PAH.

What are the mechanisms in a chronic hypoxia mouse model of severe PAH? Single-cell RNA sequencing at different time points helped define what was happening at each stage.

Current status: Disease-specific endothelial cell populations appear during the onset and progression of PAH. “Activated arterial” endothelial cells are involved in obliterative arterial remodelling due to uncontrolled cell proliferation. Surprisingly, senescent endothelial cells are found in these activated cells, even very early in the disease.

Senescent cells are resistant to cell death and secrete cytokines and other pro-inflammatory molecules which could contribute to the progression of PAH. But, senescent cells are also vital for tissue repair. Senescence can be modified either by modifying the senescence-associated secretory phenotype (SASP) or by targeting senolytic pathways.

So, is senolytic therapy with the drug ABT-263 beneficial in PAH models? One paper that used ABT-263 late in PAH concluded that it was beneficial. Another paper used ABT-263 early in the disease and found it actually worsened disease progression.

How can this apparent paradox be explained? It could depend on timing of treatment, so an experiment tested ABT-263 senolytic therapy at different points in disease development.

Early (1 week) ABT-263 worsened PAH, endothelial senescence, and inflammation, likely by interfering with repair.
Mid and late (8 weeks) ABT-263 had a significant beneficial effect on hemodynamics and arterial remodelling, associated with reductions in senescent cells and inflammation.

The population of Natural Killer T (NKT) cells went up dramatically at 8 weeks in the PAH model. NKTs recognize and clear senescent cells and seem to be activated by the lipid antigen α-Gal-Cer.

As with ABT-263 therapy, activation of iNKT cells later in disease improved PAH, but the effect was very brief (~1 week). On the other hand, early NKT cell stimulation worsened PAH, consistent with differential effects on endothelial cells in early and late disease.

Therefore, in the early stages, endothelial senescence contributes to microvascular repair, but in later stages, it promotes inflammation and vascular remodelling.

Future: Senolytic therapy in PAH is critically dependent on disease stage. Since most PAH patients present with advanced disease, this still may be a beneficial strategy, but it is clearly complicated.

Exploring integrin α5β1 as a potential therapeutic target for PAH

Presented by Sarah-Ève Lemay, MSc, Laval University

Background: The extracellular matrix (ECM), a network of materials that supports and surrounds cells, plays an important role in pulmonary arterial hypertension (PAH) and other diseases. In PAH, the ECM builds up around blood vessels, making them stiffer and causing changes to the structure of the arteries.

Integrins are proteins that help cells attach to the ECM. They also control important cell activities, including survival, growth, movement, and division. However, their role in PAH has not been well studied.

Current status: Researchers studied integrins in pulmonary artery smooth muscle cells (PASMCs) from people with PAH. They found that integrin α5β1 was the most abundant integrin in these cells. Higher levels of α5β1 were also linked to more severe PAH.

The researchers then investigated what would happen if α5β1 activity were reduced. They tested a new drug, MRT1, which mainly targets α5β1. The drug reduced the growth of PASMCs and made the cells less resistant to programmed cell death, a natural process that removes damaged or unnecessary cells.

In several rat models of PAH, MRT1 reduced the severity of the disease and was well tolerated. Its effects were similar to those of the standard treatments macitentan and tadalafil. When MRT1 was combined with standard treatment, the results improved further. MRT1 also reduced the structural changes in the blood vessels associated with PAH.

Blocking α5β1 with MRT1 interfered with two important steps in cell division: the separation of centrosomes, which help organize cell division, and the completion of mitosis, when one cell divides into two. This may help explain why MRT1 slows the growth of smooth muscle cells in PAH.

The team then developed a targeted antibody called mAB4, which blocks integrin α5. Tests in rats showed that this antibody improved blood flow and pressure measurements and reduced harmful changes in blood vessel structure. Combining the α5-blocking antibody with sotatercept produced even greater benefits.

Further experiments using human cells and thin slices of right-ventricle tissue also showed reduced cell growth, less resistance to programmed cell death, and less fibrosis (the buildup of scar-like tissue).

Future: Integrin α5β1 could be a promising target for new PAH treatments. By blocking this protein, researchers may be able to reduce the excessive growth of smooth muscle cells, limit damage to blood vessels, and improve the effects of existing treatments.

Spotting CTEPH

Presented by Dr. Micheal McInnis, University of Toronto

Background: In radiological analysis of people with known or suspected pulmonary hypertension, groups 2, 3, and 5 can be easily eliminated, but how can we distinguish between groups 1 (pulmonary arterial hypertension) and 4 (CTEPH)?

Current status: Radiographical signs of CTEPH include:

Signs of pulmonary hypertension
- Right ventricle is larger than left ventricle (ratio greater than 1)
- The muscular wall of the right ventricle is thicker than 4 mm
- The main pulmonary artery carrying blood from the heart to the lungs is wider than 2.9cm
Signs of chronic pulmonary embolisms
- Eccentric thrombus: a clot attached to the side of a pulmonary artery, often crescent-shaped, that partially blocks blood flow
- Slits and webs: thin, line-shaped or web-like structures inside a pulmonary artery that indicate previous blood clots
- Complete blockages and pouch-like defects: sudden changes in the width of a pulmonary artery, where the vessel ends in a complete blockage or a pouch-like shape
Signs in the lungs and bronchi
- Mosaic lung attenuation: a patchwork appearance, with areas of the lung showing different levels of blood flow or air supply
- Pulmonary infarcts: damaged areas of lung tissue caused by the loss of blood supply, often due to a blocked blood vessel
- Enlarged (wider than 1.5mm) and twisted bronchial arteries usually arising from the descending thoracic aorta or arch
- Enlarged bronchi.

Proximal CTEPH (in the main pulmonary arteries) can often be surgically removed, but clots in smaller, more distant arteries are more difficult to treat. CT scans overestimated and underestimated surgical disease levels at similar rates.

To distinguish between CTEPH and chronic thromboembolic pulmonary disease without PH, look at the right ventricle to left ventricle ratio, the main pulmonary artery diameter, and the presence of mosaic lung attenuation.

Ongoing research using non-contrast CT densitometry shows that CTEPH patients had lower lung density compared to PAH patients, and that centrilobular ground-glass opacities are a distinctive signature of PAH and account for the difference.

Future: Machine learning to find relationships and predict disease severity has not worked well yet. Spotting CTEPH takes skill and experience!

2025 Medical Think Tank

Why is my patient short of breath? Dyspnea after pulmonary embolism

Presented by: Dr. Devin Phillips, York University

Background: Some people continue to feel short of breath (dyspnea) even after recovering from a pulmonary embolism (PE). In fact, a study found that about one in three PE patients who did not have pulmonary hypertension still experienced significant breathlessness. This ongoing symptom often limits exercise ability and lowers quality of life.

Current status: When we exercise, our body automatically tells us to breathe more. For people who have had a PE, this “drive to breathe” is often stronger than normal. That means they may feel breathless more quickly than others, sometimes reaching severe breathlessness at only half the activity level of people without PE. This shortness of breath is thought to come from the body being more aware of the extra effort needed to breathe. Researchers are exploring different ways to help: exercise programs can improve fitness and quality of life (though not always the breathlessness itself), pulmonary endarterectomy (PEA) surgery has been shown to reduce symptoms and improve breathing capacity, and new medications are showing early promise in helping patients breathe easier and tolerate more activity.

Future: Researchers are now using new exercise testing methods to better understand how the heart and lungs interact in people who still struggle with breathlessness after a PE.

Hemodynamic phenotyping of pulmonary hypertension

Presented by: Dr. Susanna Mak, UHN Pulmonary Hypertension Program, Toronto

Background: Phenotypes are patterns of characteristics that tend to remain consistent. In pulmonary hypertension (PH), this often refers to blood flow measurements, called hemodynamics. Over the past 15 years, the way PH is defined has changed. Most importantly, PH is now diagnosed when mean pulmonary artery pressure (mPAP) is greater than 20 mmHg, rather than the older cutoff of 25 mmHg.

Current: The current definitions of PH have both strengths and challenges. The new threshold of 20 mmHg is well supported by research showing that healthy individuals do not exceed this level. Another advance is the reintroduction of an “exercise PH” definition, which helps identify patients whose pressures rise abnormally during activity and provides important information about prognosis. On the other hand, there are ongoing challenges in how certain pressures are measured, and the “normal” cut-off values may not be as precise as once thought. These definitions also work better for PH specialists than for heart failure specialists, since patients with left heart disease often show hemodynamic patterns that are harder to interpret and can look similar to those of healthy individuals.

Future: Looking ahead, refining hemodynamic measurements could help doctors better estimate prognosis, especially in patients at intermediate risk. Expanding phenotyping to include heart function and other features of the pulmonary vessels may also provide a more complete picture of PH.

Inflammatory mechanisms in pulmonary arterial hypertension

Presented by Dr. Neil Goldenberg, SickKids Research Institute, Toronto

Background: Pulmonary arterial hypertension (PAH) involves ongoing inflammation in the blood vessels of the lungs. This chronic inflammation causes the vessel walls to thicken and narrow. Researchers are exploring whether controlling inflammation could slow or even reverse these changes in PAH patients.

Current: In PAH, certain stressors—like low oxygen levels—trigger cells to release proteins that increase inflammation and cause some cells to die in a process called pyroptosis. Blood cells from PAH patients are more sensitive to this response, which may worsen inflammation and damage in the lungs. Reactive oxygen molecules appear to contribute to this heightened sensitivity. Early research shows that targeting a key protein involved in this process, called gasdermin D, can reduce both inflammation and cell damage, offering a possible way to protect lung vessels.

Future: Researchers are now developing a drug that specifically blocks gasdermin D to see whether this approach can help reduce inflammation and improve outcomes for people with PAH.

Biomarkers in pulmonary hypertension

Presented by Dr. Athénaïs Boucly, Université Paris-Saclay

Background: Biomarkers are objective indicators of medical status which can be measured accurately and reproducibly. They can be tissue biomarkers or circulating biomarkers and can be cellular or molecular.

Current: There are three types of biomarkers: diagnostic, prognostic (anticipating clinical events), or theranostic (predicting response to a specific drug).

Diagnostic biomarkers: We can screen for pulmonary hypertension using the DETECT algorithm, using biomarkers serum ACA, serum NT-proBNP, and serum urate. This helps move through the diagnosis algorithm, although no specific biomarker informs a pulmonary hypertension diagnosis. Once a diagnosis is made, biomarkers can be used in a more focused way or in screening. Proteomic profiles can identify pulmonary hypertension subgroups, but this is not used in clinical practice (yet).

Prognostic biomarkers:

A proteomic prognosis score identified six prognostic proteins, independent of 6MWT and NT-proBNP.
Inflammatory cytokines have been validated as prognostic biomarkers independent of functional class, 6MWT and NT-proBNP.
Activin A is a predictive factor of residual pulmonary hypertension after pulmonary endarterectomy (PEA) in CTEPH.
A study in ICU for patients with right heart failure found interleukin-6 and uric acid can be used as prognostic biomarkers.

Theranostic biomarkers:

Currently, no biomarkers predict response to therapies targeting the nitric oxide, endothelin 1, and prostacyclin pathways.
Three biomarkers that predict rituximab response in systemic sclerosis-associated pulmonary arterial hypertension have been identified.
One study looking at the effect of sotatercept on 3000 circulating biomarkers in PAH found 23 proteins expressed differently over time with sotatercept vs. placebo. Another study used a similar approach looking at seralutinib.
Using the plasma proteome and looking at proteins that differ between pulmonary hypertension patients and controls, a study identified 4 clusters strongly associated with survival. Patients in different clusters had different pathways upregulated, which might indicate which treatments will target their disease most effectively.

Future: The ultimate goal is to find theranostic biomarkers that can be used to tell who will respond to which treatment.

Group 3 pulmonary hypertension: A focus on PH-ILD

Presented by Dr. Sarah MacIsaac, Dalhousie University

Background: There are evolving definitions of group 3 pulmonary hypertension (pulmonary hypertension associated with interstitial lung disease, or PH-ILD). ILD is complex and includes many distinct disorders, but the key feature for those that relate to pulmonary hypertension is fibrosis. Some 80% of ILD patients will develop pulmonary hypertension; this is not a small problem. It affects the whole vasculature, not just the arteries.

Current status:

PH-ILD patients experience many barriers to reaching a PH clinic. However, it is crucial to distinguish PH-ILD patients, as this diagnosis fundamentally alters the therapeutic approach and patient management. PH-targeted therapies can harm patients with specific disease characteristics that predispose them to ventilation-perfusion mismatch.

We need a better approach to select patients for targeted therapy:

Using advanced imaging techniques for quantifying vasculature.
Assessing right heart morphology and function that appears disproportionate to the severity of lung disease.
Analyzing the FVC/DLCO ratio to isolate gas transfer defects from parenchymal vs. vascular causes.
Identifying the degree of fibrotic restriction that may limit response to treatment.
Investigating serum biomarkers.

Patients with severe pulmonary hypertension but only mild ventilatory impairment show the most favourable responses to pulmonary arterial hypertension medications, leading to a better prognosis.

The 7th World Symposium on Pulmonary Hypertension suggested six domains across which, considered together, a patient might tend to fibrosis (favouring no PH therapy) or vasculopathy (favouring PH therapy). Suggested treatments are PDE5 inhibitors (a study shows longer survival) and inhaled treprostinil.

Future: From a biochemical pathway perspective, there’s a substantial impetus to try sotatercept in PH-ILD patients.

2024 Medical Think Tank

Risky Business: How can Risk Scores Inform Clinical Practice

Presented by Dr. Ray Benza, FACC FAHA

Background: Average survival in pulmonary hypertension has improved, but we still need to do better. Further changes in survival may depend on changes in how pulmonary hypertension is managed as well as new drugs. The goal of risk assessment is to have patients achieve low risk status.

Current status: Develop a strategy with tools to stratify risk, predict survival, and guide disease management decisions in pulmonary arterial hypertension. Looking at risk affects real-life decisions that affect the aggressiveness of treatment -- this supplements clinical gestalt in experienced providers and serves as a decision tool for less experienced providers. Identifying issues in patients before symptoms become noticeable allows proactive treatment and prevents hospitalizations. However, there are several ways of calculating risk scores, and different methods tend to either over- or under-estimate risk in different risk populations. The REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) tool for risk assessment has relatively good predictive power and monitoring this score continuously helps assess a patient’s relative risk of clinical worsening.

Future: Advanced statistical approaches, including Bayesian analysis, can enhance predictive abilities and amplify clinical experience. Also being explored are ways to include right ventricular (RV) imaging, genomics and biomarkers, and remote real-time monitoring in risk stratification.

Tough Conversations: Patient Insights and Clinical Implications

Presented by Andrea Gardner, RN BSN, & Brooke Paulin

Background: As pulmonary hypertension is a serious and progressive disease, patients with pulmonary hypertension sometimes need to have "tough conversations" with their healthcare providers -- conversations that are emotional and with potentially negative content, such as at diagnosis. What can make these conversations better, from a patient perspective?

Current: Taking the time and space to build a relationship with patients, making eye contact, listening to patients' experiences and opinions, and not rushing visits are all appreciated by patients. Research shows that healthcare provider compassion is an evidence-based intervention (in conjunction with usual medical therapies) with many positive outcomes. It is not time-consuming -- in one study, a compassionate appointment script was only 40 seconds longer than a strictly fact-based script.

Future: If you are a healthcare provider, incorporate expressions of compassion into your clinical practice. Tools and trainings are available. Read more at, for example, the Compassion Research Lab (https://www.compassionresearchlab.com/) and the Schwartz Centre for Compassionate Healthcare (https://www.theschwartzcenter.org/). What you say, how you say it, and where you say it matters.

Opportunities During Onboarding of Sotatercept

Presented by John Granton, MD FRCPC

Background: Now that sotatercept is approved, what data can we work together to collect to ensure we are equipped to contribute usefully to the state of knowledge about its effects?

Current: This is an opportunity for Canadian pulmonary arterial hypertension programs to work together to improve the understanding of the drug, the condition, and how sotatercept improves cardiac systems.

Some collaboration opportunities:

Examine what is happening at the tissue level with exposure to sotatercept. Unlike calcium channel blockers, with sotatercept no particular improvement in cardiac output was observed, although pulmonary arterial pressure and thus pulmonary vascular resistance improved. Other measures such as peak oxygen consumption (peak V02) and hemoglobin also improved. Sotatercept seems to increase the ability of exercising muscles to use oxygen.
Better understand the mechanisms contributing to telangiectasias.
Examine sotatercept's effects on right ventricular function, genomics, proteomics, and other -omics.
Examine whether there is any missing information around hemodynamics.
Understand why some people respond very well to sotatercept and others do not and develop ways to predict a patient's probable response.
Follow up on patient priorities.

It is critical to start collecting data now, as sotatercept is being introduced, so we can answer these important research questions.

Future: Canadian centres contribute to the state of knowledge about sotatercept's effects in patients with pulmonary arterial hypertension.

Comorbidities in Pulmonary Arterial Hypertension

Presented by Jason Weatherald, MD MSc

Background: The session discussed the different pulmonary arterial hypertension phenotypes and reviewed recent data on the important relationship between comorbidities, treatment selection, and response.

Current: The age of pulmonary arterial hypertension (PAH) patients at the time of diagnosis has increased over time, and as people age, they accumulate comorbidities, so it is not surprising that PAH patients may have other medical conditions.

Guidelines suggest that pulmonary arterial hypertension patients with cardiopulmonary comorbidities (obesity, diabetes, high blood pressure, heart disease, lung disease) at diagnosis should be treated differently regardless of the severity of the comorbidities, as it can be hard to distinguish PAH patients with these comorbidities from group 2/3 patients and they may have more adverse events and/or worse tolerance of treatments. A correct diagnosis is key. The guidelines recommend that patients with comorbidities start on one PAH therapy, while patients without comorbidities start with two PAH therapies (dual therapy).

However, recent studies have found that newly diagnosed people with only one or two comorbidities responded to dual therapy similarly to people without any comorbidities. Similarly, in patients with ongoing pulmonary arterial hypertension, having a couple of comorbidities didn't seem to have much effect on people’s response to additional treatments.

Treatment effects may be less in patients with comorbidities, but the effect is not zero and can still be quite meaningful.

Future: An individualized approach is needed for patients with pulmonary arterial hypertension and comorbidities. More work is still necessary, but right now it seems that for patients with group 1 pulmonary arterial hypertension and one or two cardiovascular comorbidities, the treatment approach should probably be the same as for patients without comorbidities.

2023 Medical Think Tank

These research summaries were written by Dr. Sanjay Mehta, MDCM, FRCPC, Founding Board Member, Past President and Eternal Friend of PHA Canada. Thank you to Dr. Mehta for volunteering to “translate” research updates from the 2023 meeting so that you can better understand some of the incredible pulmonary hypertension research taking place in Canada.

Canadian PH Registry (CPHR): Where We Are and Where We Are Going

Presented by Dr. John Swiston, MD, FRCPC, VGH Pulmonary Hypertension Clinic, Vancouver, BC

Background: A patient registry, such as the Canadian Pulmonary Hypertension Registry, is an organized system to collect data on a specific group of patients and serves as a vital tool for clinical research. CPHR could help PHA Canada and the Canadian pulmonary hypertension community better understand the nature of Canadian PH patients by finding out who is getting diagnosed, where they are in the country, and their treatment regimes, as well as capturing important real-world data on patients’ clinical status and outcomes.

Current status: CPHR already has data from more than 2,000 Canadian PH patients. These are largely WHO group 1 PAH and group 4 CTEPH patients from 13 Expert PH Centres, including 11 adult and two pediatric centres. 68% of enrolled PH patients are female, and most patients are aged 50 – 75. CPHR already supports Canadian PH research, including the publication of three research articles and six abstracts, and five ongoing studies using CPHR data. Most of these studies involve collaborative work across several Expert PH Centres. CPHR also permits Canadian PH researchers to collaborate globally, for example, through «PHederation,» a public-private partnership for PH scientific collaboration across a network of realworld data sources such as CPHR. CPHR also facilitates new projects and partnerships with corporate sponsors, which brings more research support.

Future. Funding from PHA Canada will support active efforts to capture data from patients in all 22 Canadian Expert PH Centres.

Chronic Thromboembolic PH (CTEPH): Patient Outcomes after Pulmonary Endarterectomy

Presented by Dr. Marc de Perrot, MD, MSc, FRCSC, UHN CTEPH Program, Toronto, ON

Background. CTEPH is a common and important cause of pulmonary hypertension which develops following recurrent or multiple pulmonary emboli (=blood clots in the lungs). CTEPH must be diagnosed— based on clear Canadian clinical practice guidelines—to provide patients with effective therapies, including potentially a complete cure of CTEPH using surgical pulmonary endarterectomy (PEA).

Current status. Since 2005, the UHN CTEPH Program in Toronto has performed PEA in more than 500 CTEPH patients, ranging in age from 3 – 89. PEA significantly improves the severity of PH and right-ventricular (RV) heart failure, and clinical benefits include fewer symptoms and functional limitations, a better quality of life, and markedly improved survival (e.g., 87% after five years; 79% after ten years). PEA is a major surgery, with an overall risk of death of 2.5 % and a higher risk in CTEPH patients with more severe PH and RV failure. PEA is most effective in CTEPH patients with larger blood clots in the main pulmonary arteries. PEA also benefits CTEPH patients with smaller clots, who are most often female; these patients may need PH-targeted medications before PEA and are two times more likely to need PH-targeted medications for persistent CTEPH following PEA.

Future. An increasing number of Canadian CTEPH patients are eligible for the dramatic benefits of PEA surgery, including a potential cure. However, some CTEPH patients with more severe PH and RV failure, or smaller blood clots, should be considered for PH-targeted medications before or after PEA, and possibly alternative therapies, such as Balloon Pulmonary Angioplasty (BPA) to open plugged pulmonary artery branches.

Future Therapies for PAH: What’s on the Horizon?

Presented by Dr. Sanjay Mehta, MDCM, FRCPC, Southwest Ontario PH Clinic, London, ON

Background. Over more than 25 years of research and drug development, ten different PH-targeted medications have become available in Canada. Many Canadians living with pulmonary hypertension have benefitted with fewer symptoms and limitations, better quality of life, and longer survival. Yet, many PH patients remain very ill and need new therapies. The current medications target three pathways in pulmonary arterial hypertension: the prostanoid, endothelin, and nitric oxide (NO).

Current status. Active research has identified other key scientific abnormalities in PAH, which are now being targeted in human clinical trials. For example, the thickening and blockages of the blood vessels in the lungs (=pulmonary arteries) are due to the uncontrolled growth of smooth muscle cells and endothelial cells. Many chemicals in the body stimulate the growth of cells and can be targeted by medications. The drug sotatercept, injected under the skin (=subcutaneously), soaks up some of these chemicals (GDFs, activins) and improves many aspects of PAH, possibly reducing cell growth. There are many other exciting new therapies in current clinical studies, including kinase inhibitors (inhaled seralutinib and imatinib) and several Canadian-developed potential therapies, including olaparib (PARP-1 inhibitor), apabetalone (BRD4 inhibitor), intravenously injected gene-enhanced endothelial stem cells.

Future. Ongoing research is already developing new therapies, and we expect many more advances in PH treatment over the next five years, helping us further improve the lives of all Canadians living with PH.