Chest pain, shortness of breath and profound fatigue. Every year, thousands of women experience these symptoms despite having no obstructed coronary arteries. Many leave the hospital without a diagnosis, even though they have an underlying cardiovascular condition. Researchers at UMC Utrecht aim to change this. Supported by the international Wellcome Leap VISIBLE program, they are developing an AI-powered blood test to enable faster, less invasive diagnosis of coronary microvascular dysfunction (CMD).
When patients present with chest pain, physicians first evaluate whether a major coronary artery is narrowed or obstructed. However, in many women the problem does not lie in these larger vessels, but in the heart’s smallest blood vessels. This type of chest pain is known as ANOCA (angina with no obstructive coronary arteries).
“The frustrating part is that problems in these tiny blood vessels cannot be detected using standard diagnostic tests,” says postdoctoral researcher Tim Sakkers. “As a result, many women have spent years being told that their symptoms were probably caused by stress or menopause, while they actually have cardiovascular disease.” As a result, many patients remain undiagnosed for years and do not receive the treatment that best matches their condition.
The UMC Utrecht team is therefore developing a new diagnostic test for coronary microvascular dysfunction (CMD), one of the leading causes of ANOCA. In CMD, the small blood vessels within the heart muscle do not function properly, leading to symptoms such as chest pain and shortness of breath.
Diagnosing CMD currently requires specialized invasive coronary function testing. During this procedure, physicians insert a catheter into the coronary arteries and administer medication to temporarily provoke symptoms. “This diagnostic procedure is invasive, costly, painful, and not widely available,” Sakkers explains.
The REVEAL-CMD project aims to replace this procedure with a simple blood test. “From a single blood sample, we can measure millions of biological molecules,” Assistant Professor Ernest Diez Benavente explains. “Using artificial intelligence, we can identify the combination of biomarkers that most accurately predicts whether a patient has CMD.”
The researchers also aim to distinguish between different subtypes of CMD. “The most effective treatment depends on the specific subtype a patient has,” says Diez Benavente. “By using multiple subsets of biomarkers, we not only make diagnosis easier but also help physicians select the most appropriate treatment more quickly.”
Hester den Ruijter, Tim Sakkers and Ernest Diez Benavente
The development of this novel diagnostic test brings together expertise from multiple disciplines at UMC Utrecht under the leadership of Hester den Ruijter, Professor of Cardiovascular Disease in Women.
Interventional cardiologist Tim van de Hoef provides the clinical expertise. He treats patients with CMD and leads the clinical studies that will validate the new blood test. Diez Benavente develops the AI algorithms that identify the most promising combinations from millions of biological molecules.
Sakkers investigates the biomarkers and focuses on translating the technology into a spin-off company. “My ultimate goal is to bring our scientific discoveries into society,” he says. “That is how we can ultimately make this test available to patients. With the combined expertise of our team, I’m convinced we can make that happen.”
The REVEAL-CMD project is part of the international Wellcome Leap VISIBLE program. Within the program, twelve research teams from around the world are working together to develop new ways to improve the diagnosis and treatment of cardiovascular disease in women. “This allows us to share our knowledge and data with the other research teams, accelerating the development and validation of this diagnostic test,” says Diez Benavente.
The researchers hope that a simple blood test will end the years-long search for a diagnosis. “With this project, we are addressing an important blind spot in women’s cardiovascular care,” Sakkers concludes. “Our goal is to improve women’s quality of life and prevent them from spending years without the right diagnosis and treatment.”
UMC Utrecht is one of twelve research teams worldwide participating in the Wellcome Leap VISIBLE program. A total of 55 million dollars in funding is available across the participating research teams, which are working to improve the diagnosis and treatment of cardiovascular disease in women.
