How a Growing Research Registry Is Shedding Light on a Hidden Heart Condition.

Our registry is helping more people get care for an underrecognized heart condition that sometimes causes patients years of unexplained pain and discomfort. 

Imagine experiencing chest pain, shortness of breath, and fatigue for years, only to be told your heart tests look normal. That's the reality for many people living with coronary microvascular dysfunction, an often-overlooked condition affecting the heart's smallest blood vessels.

For decades, cardiologists have known that some symptoms of a serious problem with the heart’s blood supply don’t show up on standard testing. We called it “chest pain syndrome X,” and we couldn’t give patients a good explanation for their symptoms. 

That began to change when we started offering a specialized test called coronary functional testing in 2022. Unlike traditional heart tests, it allows us to evaluate the heart's smallest blood vessels—areas where problems can exist even when larger arteries appear normal. For many patients, the test provides answers that standard testing cannot.

Today, we know that “chest pain syndrome X” is actually coronary microvascular dysfunction (CMD). Patients come to our centers from throughout the East Coast to get this test, and we can often give them answers they’ve been seeking for years. 

MedStar Cardiovascular Research Network, a division of both the MedStar Health Research Institute and the MedStar Heart and Vascular Instituteare supporting us as we build a secure database called the Coronary Microvascular Disease Registry. This data has already helped us shed light on this once-mysterious condition. 

By teaming up with patients and researchers across the country, we’re learning more about CMD so we can spot it sooner and treat it more effectively.

A condition hidden in the heart’s smallest vessels.

Cardiologists are very good at diagnosing conditions that affect the heart and its major blood vessels. But CMD affects a smaller part of the heart’s plumbing: the microscopic vessels that supply the heart muscle with oxygen-rich blood.

When these tiny vessels malfunction, tighten, or spasm, the heart can’t get the blood flow it needs. This can cause symptoms such as:
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• Chest pain

• Difficulty sleeping

• Discomfort in the jaw, neck, or abdomen

• Severe shortness of breath

• Unexplained fatigue

A coronary angiogram is a special X-ray that looks for blockages in the heart's larger arteries. But for about 40% to 50% of patients who undergo the test because of chest pain, the results show no major blockages—even though their symptoms are very real.

When an angiogram comes back clear, CMD is the culprit about half the time. Studies estimate that could add up to as many as 4 million people in the U.S. with the condition, two thirds of them women.

Related: Read “Coronary Microvascular Dysfunction: New Diagnostic Tools Offer Quick Answers and Treatment.”

Finding answers when standard heart tests come back normal.

A standard angiogram is great at spotting major blockages in large heart arteries. But if your symptoms are caused by CMD, those arteries often look completely clear. Traditional testing can miss CMD because the problem isn’t caused by a clogged main artery.

Coronary functional testing fills the gap. Instead of taking a picture of your large arteries, this specialized test evaluates how the smallest vessels react and function. It uncovers hidden issues that other scans can overlook, giving patients a clear diagnosis. For some people, it can rule out the heart as the cause of chest pain.

Now that we can spot CMD more easily, we’re tracking patients over the long term to study the condition on a larger scale.

Building a registry to answer big questions.

What started at two hospitals has grown to a national network of eight sites with about 750 participants. International locations will soon join us. Expanding this registry is about more than growing our numbers. A larger, more diverse group of patients gives us a much clearer picture of how CMD behaves across different people. This helps us answer bigger questions about the disease much faster. 

My colleagues Dr. Hayder Hashim and Dr. Ron Waksman were instrumental in creating the registry. Together, we recognized the need for a larger, collaborative effort to better understand CMD and improve care for patients living with this often-overlooked condition.

Any patient undergoing coronary functional testing at a participating site can join, even if testing shows they don’t have CMD. By tracking participants’ health histories, test results, and annual checkups over five years, we can see how symptoms evolve over time. 

Analyzing these patterns across hundreds of real-world cases helps us improve diagnosis, evaluate treatments, and make sure future patients get the accurate answers they deserve much sooner. 

Related: Read “Global CMD Registry Research Helps Understand Chest Pain Before Tragedy Strikes.”

What the registry is helping us learn about CMD.

The data we’re collecting is doing more than expanding research. It’s actively changing how we care for patients. By uncovering what drives CMD, we can better predict who is at risk and find more effective ways to protect their health, for example:
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• CMD affects more than just the heart: We’ve discovered strong links between microvascular damage and conditions such as type 2 diabetes, chronic kidney disease, and aging. Recognizing these patterns helps doctors spot CMD earlier in patients who are already managing other health conditions.

• Inflammation plays a role: Patients with autoimmune diseases such as lupus or rheumatoid arthritis are more likely to have stiff, narrow microvessels. Connecting these dots allows us to explore the role of anti-inflammatory therapies in treatment. 

• Cancer therapies can trigger hidden heart issues: Certain modern cancer drugs (such as immune checkpoint inhibitors) can cause inflammation in the tiny vessels. This means cancer survivors with unexplained chest pain could have CMD, opening the door to targeted cardiac care.

• CMD explains complex symptoms like irregular heartbeats: When tiny vessels malfunction, they starve the heart muscle of oxygen. This doesn’t just cause chest discomfort, it can alter how the heart beats. Understanding this helps us intervene early to protect long-term heart function and improve quality of life.

Beyond ‘normal’ tests: One patient’s search for a diagnosis.

Morton Sherman is used to solving complex problems. A retired school superintendent, the 76-year-old father, grandfather, and lifelong athlete from Virginia didn’t expect a COVID-19 infection in 2022 to become the start of a long and frustrating search for answers.

After recovering from COVID, Sherman began experiencing severe dizziness, cold hands and feet, shortness of breath, and chest pain during everyday activities. As his symptoms escalated, he went to the emergency room more than once. Yet all the standard cardiac tests showed his heart was normal. 

Month after month, Sherman visited specialists and emergency rooms looking for an explanation. Despite ongoing symptoms, he continued leaving appointments without answers.

“Nobody knows your body better than you,” he said recently. “If you’re not feeling well, don’t accept ‘we don’t know’ as an answer.”

As Sherman kept searching, he found that specialists at many leading medical centers across the country had very long waitlists. Then he found Brian Case, MD, at MedStar Health.

“Dr. Case made an appointment within a couple of days,” Sherman explained. “He was this amazing breath of fresh air.”

Using coronary functional testing, Dr. Case evaluated the tiny blood vessels in Sherman's heart, areas that standard heart tests often cannot fully assess. The test revealed the cause of his symptoms: coronary microvascular dysfunction (CMD). For Sherman, the diagnosis provided something he had been seeking for months: answers.

It also provided a path forward. With a diagnosis in hand, he was able to begin targeted treatment and better understand what was happening in his body.

Sherman also enrolled in the CMD Registry. He wanted to contribute his health data so researchers can spot patterns and help future patients get diagnosed sooner.

“Knowing that Dr. Case and his team are actively researching it makes a world of difference,” Sherman said. “It gives you peace of mind knowing capable people are looking closely at this.”

Growing toward screening and improved treatment.

Reaching our goal of 2,000 participants in the registry is key to transforming how we manage CMD. A registry of this size gives us the statistical power to spot subtle patterns across diverse groups of people.

Instead of reacting to symptoms after they begin, having more participant data allows us to build predictive models. With this data we can identify who is at high risk and step in with preventive care before CMD can disrupt their lives.

For example, we’re zeroing in on early biological markers that could signal trouble ahead. Our research reveals that high levels of fat around the heart we can see on a standard CT scan can be an early warning sign of CMD. Spotting these warning flags across a larger patient population gives us a crucial window to help before severe symptoms develop.

A larger pool of participants also helps us compare how different sub-groups of people respond to specific treatments. The registry enables us to match each patient with the treatment most likely to bring them relief, including:
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• Weight and blood sugar medications: Options like Ozempic and Wegovy could reduce inflammation and improve blood vessel function

• Heart and kidney drugs: Medications such as Jardiance and Farxiga can protect the heart muscle and improve circulation

• Medical devices: A specialized implanted device called a coronary sinus reducer redirects blood flow inside the heart when medications aren’t enough

Partnering with patients to find answers.

Every patient with unexplained heart symptoms deserves answers and options. That's why we've built this registry and why we're continuing to expand it. By working alongside patients, doctors, and researchers across the country, we’re turning unique stories into collected data that can advance science and help more people get accurate answers and targeted heart care.