Cardiovascular interventions, such as open-heart surgery, stents and medications, have undoubtedly improved the lives of many patients. Still, heart problems like coronary microvascular disease (MVD), or microcirculatory disease, often go undiagnosed.
Even the heart’s smallest blood vessels can malfunction, causing restricted blood flow and oxygen to the heart muscle. This mismatch between oxygen supply and demand can lead to ischemia.
Approximately one-third of patients who present with chest pain and all the hallmarks of heart blockages don’t actually have obstructive disease.
Thinking differently about ischemic heart disease evaluation
Angina with nonobstructive coronary arteries (ANOCA) is a cluster of microvascular conditions that challenges traditional definitions of heart disease. In ANOCA, damage to the inner walls of tiny microvessels causes spasms that disrupt blood flow, whether or not physical exertion is involved.
“When a patient has perfectly normal arteries with no blockages, but their vessels suddenly spasm, it can feel like a heart attack,” says interventional cardiologist Amarnath Annapureddy, MBBS. “Frequently, by the time they are tested, everything can look normal again. This makes diagnosis and management quite challenging.”
While anyone can experience ANOCA, women are at higher risk, especially between the ages of 30 and 60. Women are frequently misdiagnosed or dismissed, often spending years searching for answers to their mysterious symptoms. Standard testing like stress tests, scans and angiograms can miss ANOCA, leading to repeat testing, ineffective medications and life-altering impacts.
“Some of these women are high-functioning people who suddenly can’t perform daily activities, resulting in a devastating impact on their lives,” says Dr. Annapureddy. “Conventional diagnostics have been limited in these cases, leaving both doctor and patient frustrated. I realized the need for additional specialized testing to help these patients get their lives back.”
For many patients, the inability to receive a definitive diagnosis has led to disability, early retirement and poor quality of life.
It was because of this gap in diagnostics and research that Dr. Annapureddy decided it was time to dig deeper, ask more complex questions and look beyond what standard diagnostic imaging could reveal.
The Comprehensive Coronary Physiology Program
In 2024, UNMC acquired the Abbott Coroventis CoroFlow System, an advanced platform that measures coronary microvascular function in real time. The first of its kind in Nebraska, it uses advanced, comprehensive coronary function testing to diagnose ANOCA.
“We are pioneering in this space and take it very seriously,” says Dr. Annapureddy. “This diagnostic approach takes a lot of time and persistence, but the goal is to help patients regain control. When patients receive clarity, often after years of testing, it can change their lives.”
To date, the program has successfully diagnosed approximately 80% of more than 70 patients, enabling targeted treatment. Case studies show positive outcomes, including meaningful symptom improvement. Depending on the patient, this may mean the ability to stop unnecessary medications and make timely referrals to the appropriate specialist to achieve successful treatment.
Testing protocol includes:
- An acetylcholine challenge test to induce vessel spasm and confirm microvascular dysfunction.
- A pressure wire test to measure blood flow, pressure and assess microvascular resistance.
Patient candidates: Who to refer
Early referral can make all the difference. Patients often present with atypical symptoms, including pain at rest with high disability. About 90% of patients in the program have been middle-aged women, which is consistent with global data.
Referral guidelines:
- Stable angina: After one to two failed medication trials for persistent, debilitating symptoms.
- Acute, unstable presentation: Immediately after a heart attack (MINOCA-Myocardial infarction with no obstructive coronary artery disease).
While the program has seen positive outcomes in many patients, Dr. Annapureddy notes that some cases remain challenging to manage. “But if you have a patient where symptoms persist, and findings don’t explain them, avoid repeating the same tests. Consider invasive coronary function testing.”
Consider referring a patient if they:
- Present with persistent, unexplained angina-equivalent symptoms after a standard workup.
- Need multiple medications without clarity on a diagnosis.
- Have atypical rest-pain angina patterns, dyspnea or fatigue without classic exertional triggers.
- Have MINOCA or ANOCA scenarios.
- Have had dramatic events without obstructive CAD.
- Have frequent or disabling symptoms (daily or several times weekly), requiring three or more medications without a firm diagnosis
- If presentation is dramatic (ACS-like episodes, cardiac arrest) even without obstructive disease.
Leading the way as a regional referral hub
The Nebraska Medicine Comprehensive Coronary Physiology Program offers a dedicated invasive coronary function testing protocol, including:
- Acetylcholine vasoreactivity and pressure and flow wire, with comprehensive follow-up.
- Team-based management, including surgery for myocardial bridging and collaboration with anesthesia for stellate or ganglion blockade when needed.
- A strong referral center ethos, emphasizing thorough phenotyping, cross-institution consults and persistence on management even when challenging.
- A program motivated by patient outcomes that is mission-driven, with a nonprofit academic approach.
The evolution of evaluation, diagnosis and management of complex conditions like ANOCA is rapidly changing the landscape for patients seeking answers to their elusive cardiac symptoms.
Dr. Annapureddy is excited to contribute to further knowledge. “I desire to bring together clinical care and research so we can not only effectively treat patients, but also generate data that will change the field and shape the future of cardiovascular care.”
Meet the specialist
Dr. Annapureddy is an assistant professor in the UNMC Division of Cardiovascular Medicine and is passionate about solving complex cardiovascular problems. His goal is to continue innovative research to improve the evaluation of ischemic heart disease and advance the understanding of ANOCA. Outside of work, Dr. Annapureddy enjoys spending time with his two active children.