RESEARCH

Medical Think Tank

Stay informed about the latest pulmonary hypertension research with summaries from our annual National Pulmonary Hypertension Medical Think Tank

The National Pulmonary Hypertension Medical Think Tank convenes pulmonary hypertension experts and other academic researchers for a think tank focused on facilitating collaboration among pulmonary hypertension clinicians and scientists, accompanied by a full day of scientific sessions sharing the latest in PH research from across Canada and beyond.

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

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.