PET Heart Scan Finds Low Flow Reserve Strongly Linked to Death and Heart Failure Risk

A single value from a cardiac scan may help identify which patients are more likely to die, suffer a heart attack, need hospitalization for heart failure, or develop a dangerous heart rhythm, even when standard ischemia measures appear reassuring. That is the key finding of a new study from Nippon Medical School in Tokyo, published in the European Journal of Nuclear Medicine and Molecular Imaging. Using nitrogen-13 ammonia positron emission tomography, or ¹³N-ammonia PET, the researchers found that patients with chronic coronary syndrome whose global myocardial flow reserve fell below 2.0 had more than four times the risk of a major cardiac event compared with those above that level, and the association remained even after accounting for relative ischemia seen on the same scan.

Myocardial flow reserve, or MFR, measures how well the heart’s small blood vessels can increase blood flow under stress. It is calculated by dividing myocardial blood flow during pharmacological stress, often induced with vasodilators such as adenosine or dipyridamole, by flow at rest. A healthy coronary system can raise flow several-fold when demand increases; an MFR of 2.0 means perfusion can only double, which is generally considered abnormal. Unlike visual perfusion images, which show regional defects only when differences in blood flow are large enough to create contrast, quantitative MFR can detect diffuse and microvascular disease that conventional relative imaging may miss.

The ¹³N-ammonia tracer has a special role in this area. Although it is short-lived and must be produced on-site with a cyclotron because of its roughly ten-minute half-life, it offers excellent extraction characteristics and has a long history in quantitative myocardial perfusion imaging. The Japanese team, led by Yoshimitsu Fukushima of the Department of Radiology, retrospectively reviewed consecutive adults with suspected or established chronic coronary syndrome who underwent ¹³N-ammonia PET/CT at their center. The study included patients scanned on two generations of PET systems, and the authors built that difference into their statistical design by stratifying the main model by scanner generation.

Among the 168 patients analyzed, 102, or just over 60 percent, had a global MFR below 2.0. These patients showed a distinct hemodynamic pattern: higher resting blood flow and lower stress blood flow than those with preserved reserve. That pattern makes physiological sense. Higher resting flow can reflect compensatory changes or altered hemodynamics, while a weaker stress response suggests the coronary microcirculation cannot increase delivery when the heart needs it. The reserve metric condenses that gap into a single number.

Over a median follow-up of 3.5 years, the study’s primary endpoint, a hard composite that excluded revascularization procedures, occurred in 28 of the 102 patients with low MFR, or 27.5 percent, compared with 5 of the 66 patients with preserved reserve, or 7.6 percent. The composite included all-cause death, non-fatal myocardial infarction, hospitalization for heart failure, and malignant ventricular arrhythmia. By leaving out revascularization, the endpoint avoided the circular problem that can affect imaging studies, where a scan finding leads to an intervention that is then counted as an event. The Kaplan-Meier curves separated clearly between the two groups, with a log-rank P value below 0.001.

A pre-specified Cox proportional hazards model adjusted for age, sex, and the summed difference score, a standard semi-quantitative measure of relative ischemia derived from the perfusion images. Even after that adjustment, low MFR remained independently linked to the composite endpoint, with a hazard ratio of about 4.52 and a 95 percent confidence interval of 1.71 to 11.92. That independence from the summed difference score is the study’s most important result: it suggests that MFR adds prognostic information beyond visible ischemia and likely reflects the status of the microvasculature and the myocardium itself.

Because the composite endpoint was heavily influenced by heart-failure hospitalization, the researchers also ran a sensitivity analysis excluding patients who already had heart failure at baseline. The association still held, with a hazard ratio of 4.17 and a P value of 0.011. This finding suggests that reduced flow reserve is not simply a marker of existing pump failure. It fits with broader evidence connecting coronary microvascular dysfunction to later heart failure, including heart failure with preserved ejection fraction, in which the heart muscle becomes stiff and fills poorly despite a seemingly normal ejection fraction. Earlier work by Taqueti and colleagues showed that global coronary flow reserve predicts adverse events independently of angiographic stenosis severity, and meta-analyses have reinforced the prognostic value of PET-based flow measurements across tracers and patient groups.

The study also addressed a technical dispute in cardiac PET: whether raw MFR should be corrected for the rate-pressure product, or RPP, the product of heart rate and systolic blood pressure used as a proxy for myocardial oxygen demand. Supporters of RPP correction say it helps account for hemodynamic differences between rest and stress imaging, while critics argue that it can alter the physiological meaning of reserve and hide true microvascular dysfunction. In this cohort, RPP correction moved 52 patients, or 31 percent of the sample, across the 2.0 cutoff, and most of those changes were downward, meaning correction pushed patients into the abnormal range. Event rates were consistent with that pattern: patients reclassified downward had a 7.0 percent event rate, while those abnormal by both the uncorrected and corrected values had a 29.0 percent event rate, with a four-group log-rank P value of 0.003.

Those reclassification numbers matter in practice. If nearly one-third of patients can change risk category depending on whether correction is used, laboratories need to be clear about which value they report. The authors conclude that uncorrected global MFR should be the main reported measure, with any RPP-corrected value clearly labeled. Their results indicate that uncorrected MFR below 2.0 identifies higher-risk patients independently of relative ischemia, and that correction, while potentially useful, should supplement rather than replace the raw physiological measure. That view aligns with recent comparative studies, including work from Houston and elsewhere on corrected versus uncorrected reserve in patients without obstructive coronary disease, as well as a multicenter analysis confirming the prognostic value of MFR for mortality in ¹³N-ammonia imaging.

The limitations are important. The study was retrospective and single-center, and the 168-patient cohort came from a Japanese population scanned across two PET scanner generations. The authors accounted for that heterogeneity statistically, but it still reflects real-world practice rather than a controlled trial. The composite endpoint, although hard, was dominated by heart-failure hospitalizations, so the findings speak most directly to heart-failure-related risk rather than sudden death or arrhythmia alone. Even so, the practical takeaway for clinicians is clear: when a quantitative ¹³N-ammonia PET study shows a global flow reserve below 2.0, that number deserves attention on its own, not just as a detail within the perfusion images. For patients with chronic coronary syndrome, microvascular reserve may be one of the strongest predictors of future outcomes.

Subject of Research: Prognostic value of ¹³N-ammonia PET myocardial flow reserve in chronic coronary syndrome

Article Title: Reduced ¹³N-Ammonia PET Myocardial Flow Reserve and Heart-Failure–Related Risk Independent of Relative Ischemia in Chronic Coronary Syndrome

Article References: Fukushima, Y., Kobayashi, R., Yodogawa, K., Shimizu, S., Imai, S., Hayashi, H., & Kumita, S. (2026). Reduced ¹³N-Ammonia PET Myocardial Flow Reserve and Heart-Failure–Related Risk Independent of Relative Ischemia in Chronic Coronary Syndrome. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-026-08183-9

Image Credits: AI Generated

Keywords: myocardial flow reserve, ¹³N-ammonia PET, chronic coronary syndrome, heart failure, coronary microvascular dysfunction, rate-pressure product, myocardial perfusion imaging, risk stratification, cardiac PET, prognosis, ischemia, nuclear cardiology

Cite Scienmag News

Ophelia Keating. (October 1, 2026). Heart Scan Warning: Low Flow Reserve on PET Quadruples Risk of Death and Heart Failure. Scienmag. https://scienmag.com/heart-scan-warning-low-flow-reserve-on-pet-quadruples-risk-of-death-and-heart-failure/

Ophelia Keating. "Heart Scan Warning: Low Flow Reserve on PET Quadruples Risk of Death and Heart Failure." Scienmag, 1 October 2026, https://scienmag.com/heart-scan-warning-low-flow-reserve-on-pet-quadruples-risk-of-death-and-heart-failure/. Accessed 1 October 2026.