Aussie researchers target first female-specific treatment for invisible heart disease

An Australian research team has secured support through Wellcome Leap’s VISIBLE programme, a global initiative investing more than US$75 million in advancing women’s cardiovascular health. The funding will underpin a new clinical trial targeting one of cardiology’s most persistent blind spots.

Associate Professor Erin Howden from UNSW Medicine & Health will lead the RESTORE trial, designed to evaluate a female-specific therapeutic approach for coronary microvascular dysfunction (CMD), a condition often described as “invisible heart disease”.

CMD affects the heart’s smallest blood vessels, which are too fine to be detected on standard angiograms. It is significantly more prevalent in women, particularly after menopause, and remains both poorly understood and inadequately treated within current cardiovascular practice.

“Up to 70% of women with chest pain who undergo angiography are told their arteries are clear, yet many will continue to live with debilitating angina, breathlessness and fatigue that limits daily life,” explained A/Professor Howden.

Despite its burden, diagnostic pathways for CMD are limited, and testing often requires invasive procedures that are not widely accessible in routine care.

“The condition can have a huge impact on women’s day-to-day lives. In addition to having debilitating symptoms, women with CMD carry an up to four-fold higher risk of major cardiovascular events,” A/Professor Howden said. “At a day-to-day level, experiencing angina or chest pain limits a women’s ability to work, with many reporting that they reduce hours or retire early. There are additional negative effects on mental health and social lives.”

At present, most women diagnosed with CMD are managed with symptom-relieving medications originally developed for men with obstructive coronary artery disease, rather than therapies tailored to the underlying microvascular dysfunction.

“Our trial will investigate whether treating oestrogen deficiency in post-menopausal women, combined with structured exercise, can improve the function of the heart’s smallest blood vessels,” A/Professor Howden said.

The study will run over 16 weeks and enrol 132 post-menopausal women across Sydney, Melbourne, and Adelaide. Participants will receive one or both interventions, with advanced cardiac MRI used to assess changes in the function of the heart’s smallest vessels.

“If RESTORE shows that transdermal oestrogen and structured exercise can repair the heart’s smallest blood vessels and improve symptoms, it could lead to the first female-specific treatment for a condition that affects millions of women worldwide. It would also change the way CMD is understood and treated from a condition often dismissed as ‘nothing serious’, to one that can be actively managed,” she explained.

Professor Cheryl Jones, Dean of UNSW Medicine & Health, said the implications extend well beyond a single trial.

“CMD has too often gone unrecognised and undertreated in women. By investigating this female-specific treatment approach for this condition, the RESTORE trial has the potential to transform care for millions of women worldwide and position Australia at the forefront of women’s heart health research.”

A/Professor Howden said the backing from the VISIBLE programme, founded by the Wellcome Trust, marks a turning point for the field.

“For decades, coronary microvascular dysfunction has been one of the clearest examples of how women’s cardiovascular disease has been overlooked,” she emphasised. “VISIBLE provides the resources to change that, and just as importantly, brings our research into a global community working on the same problem with shared data and shared research protocols. For the field more broadly, this signals something overdue – women’s cardiovascular health is now a scientific priority of the highest order, not a sub-speciality concern.”

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