Myocardial blood flow is reduced in patients with long COVID-19, according to a Houston Methodist study that could shift the focus on the virus' lingering heart effects from the muscle itself to the vascular system.

The study found that patients with heart-related long COVID-19 have a 20% decrease in their coronary arteries' ability to vasodilate, the widening of blood vessels that normally occurs in response to low oxygen levels or increases in body temperature.

"The signal that blood flow in post-COVID patients was reduced was very consistent in people with lingering COVID-19," says Dr. Mouaz Al-Mallah, director of cardiovascular positron emission tomography at Houston Methodist DeBakey Heart & Vascular Center and the study's primary investigator. "Doctors need to be on the lookout for vascular signs of the virus' residual effect."

Patients with a prior COVD-19 infection were twice as likely to have unhealthy endothelial cells, the study also showed. Patients with unhealthy endothelial cells — cells that line the inside of the heart and blood vessels — have a higher risk of heart failure, hospitalization, bypass surgery and death.

The study, published online in JACC: Cardiovascular Imaging in August, is the first to link reduced blood flow and COVID-19.

Long COVID-19, which involve a variety of symptoms that persist well after the virus has resolved, is one of the unexplained mysteries of the pandemic, afflicting an estimated 16 million Americans. There is no standard test or treatment for it.

The lingering effects often include heart-related symptoms — some studies estimate as many as 1 in 4 patients with severe COVID-19 have markers of cardiac injury and a 5- to 10-fold increase in the risk of death. Former COVID-19 patients commonly report palpitations, dizziness, chest pains and shortness of breath, and studies have found higher risks of arrhythmias, atrial fibrillation, stroke, blood clots, heart failure and heart attacks.

Initial studies suggested COVID-19's effect on the heart muscle itself was quite common. But subsequent research, larger and including more randomly selected patients, found myocarditis was actually only the cause in a very small percentage of patients.

So Dr. Al-Mallah's team investigated blood flow as a cause of heart-related long COVID-19 issues. The team analyzed PET imaging data from 393 patients, 101 of whom had lingering symptoms well after a prior COVID-19 infection. The other patients had never been diagnosed with COVID-19.

The most common reasons the patients underwent PET imaging were chest pain and difficulty breathing. Two-thirds of the long COVID-19 patients and 54% of the control patients had chest pain; 41% and 37%, respectively, had difficulty breathing.

The mean age of patients was 65. For those previously diagnosed with COVID-19, the median number of days between diagnosis and undergoing PET imaging was 190 days.

The study found patients with long COVID-19 were more likely to have reduced myocardial flow reserve (MFR), the capacity for blood flow to the heart under exertion compared to such flow at rest. MFR is a marker for poor prognosis and a higher risk of adverse cardiovascular events.

The study found reduced MFR in 58% of long COVID-19 patients and 28% of control patients. MFR normalized to the patients' rate of systolic blood pressure was seen in 44% of long COVID-19 patients and 26% of control patients.

In addition, the study showed that after a median follow-up period of 323 days, the annualized rate of major cardiovascular events was higher among former COVID-19 patients.

Dr. Al-Mallah, president elect of the American Society of Nuclear Cardiology, says he was surprised by the study findings, noting that endothelial dysfunction is a known condition in, say, diabetics, but hadn't previously been described in COVID-19 survivors.

"Doctors and patients need to be aware of the vascular system's possible role in long COVID-19," says Dr. Al-Mallah. "If you have a patient with lingering COVID-19 heart symptoms and the echocardiogram was normal and there are no blockages in the arteries of the heart, you should probably consider doing a PET stress with myocardial blood flow to assess the blood flow to the heart."

Dr. Al-Mallah acknowledges that further studies are needed to document the magnitude of microvascular dysfunction and identify possible strategies for early diagnosis and intervention. He notes that reduced MFR can determine risk when the patient presents with symptoms of coronary artery disease over and above more established factors.

Next up for Dr. Al-Mallah's team will be prospective, clinical studies, aimed at discovering longer-term outcomes in patients whose microvascular health has been affected by COVID-19, particularly long COVID-19.

The JAAC study was supported, in part, by grants from the National Institutes of Health.