Canadian PH researchers identify a gene leading to heart failure in PAH

This week is Heart Failure Awareness Week. As this year's awareness campaign says, it's not normal to be breathless!

Heart failure is, unfortunately, one of the consequences of pulmonary hypertension. The right side of the heart can adapt for a while by getting thicker and stronger, but it's hard to tell why it eventually starts to fail, and this happens at different times for different patients. Raising awareness about this serious condition is important: early detection helps people get the care they need, potentially slowing disease progression and improving quality of life.

Fortunately, researchers are working to identify pulmonary hypertension patients at higher risk of heart failure, so treatment can be adapted for them. One theory was that muscle cells in the heart ran out of energy as the right side of the heart enlarged and there weren’t enough new blood vessels to supply energy to the heart muscle. This would lead heart muscle cells to die, forming scar tissue and changing the heart’s structure. But this theory didn’t explain why the right side of the heart could recover after, for example, lung transplantation, so they kept looking for other causes.

Recently, 2023 PHA Canada Paroian Family Pulmonary Hypertension Research Scholarship winner Yongneng Zhang, along with Canadian pulmonary hypertension specialists Steeve Provencher and Sébastien Bonnet at IUCPQ and other collaborators, found that heart failure accelerated when certain support cells (myofibroblasts) became overactive, rather than when the heart muscles were not receiving enough energy to pump. They identified a particular variation of the UCP2 gene in about 30% of patients with severe pulmonary arterial hypertension (PAH)—a variation which led to lower levels of the UCP2 protein in those support cells. People with this form of the UCP2 gene experienced heart failure sooner, compared to pulmonary arterial hypertension patients with other variants of the UCP2 gene. Testing patients for this gene variation could help identify those at higher risk earlier, allowing care teams to tailor monitoring and treatment more proactively. These patients might require “more intense PAH/supportive therapies, frequent follow-ups, earlier referral for transplantation, and anticipating slower recovery after transplantation.”

Heart Failure Awareness Week is a reminder that even symptoms—like shortness of breath and fatigue—that are hard to attach to a particular diagnosis should never be ignored or dismissed. It’s also a reminder that researchers are making terrific progress in understanding and treating heart failure. By learning more about heart failure and pulmonary hypertension, we can encourage earlier diagnosis, support ongoing research, and help ensure that patients receive the right care at the right time.