Hidden Heart Risk Detected in Patients With Normal Cardiac Stress Tests

Millions of patients undergo cardiac PET stress tests each year and receive reassurance when results appear normal. But a large multicenter study published in Circulation reveals that a subset of these 'normal' patients actually carry substantially elevated cardiovascular risk — detectable only through a more refined measure of heart muscle blood flow.

The study examined 6,603 patients from an international PET registry, all of whom had normal perfusion on standard rubidium-82 stress PET imaging. Researchers compared the conventional transmural myocardial flow reserve (MFR) against a newer metric: subendocardial MFR (MFRSE), which specifically measures flow to the inner, most oxygen-vulnerable layer of the heart wall. Patients were divided into three groups — concordant-normal, discordant (normal transmural but low subendocardial MFR), and abnormal transmural MFR.

Over a median follow-up of nearly five years, 1,661 major adverse cardiovascular events (MACE) occurred. The 885 discordant patients — those with normal standard results but reduced subendocardial flow — faced a 41% higher risk of MACE and a 36% higher risk of all-cause mortality compared to the concordant-normal group. Their annualized event rate of 5.79% fell squarely between the normal group (3.99%) and the overtly abnormal group (8.35%), suggesting a genuine intermediate-risk phenotype.

For clinicians, this is a meaningful advance. These discordant patients were older and more likely to have hypertension, diabetes, and peripheral artery disease — comorbidities that may impair subendocardial microcirculation before macrovascular disease becomes apparent on conventional imaging.

The key implication: adding MFRSE analysis to standard PET reports could identify higher-risk patients currently sent home with false reassurance, enabling earlier preventive strategies. Caveats include the observational design and that the full text was unavailable for detailed review.