Reduced myocardial flow reserve on ¹³N-Ammonia PET predicts adverse outcomes independent of heart failure status

Background Myocardial flow reserve (MFR) assessed by ¹³N-ammonia PET is a strong prognostic marker in ischemic heart disease (IHD). Although both heart failure (HF) and reduced MFR are associated with adverse outcomes, whether the prognostic value of MFR differs according to HF status across the spectrum of IHD remains unclear.Therefore, this study aimed to compare MFR distribution between HF and non-HF patients with IHD and to assess whether HF status modifies the prognostic value of MFR. Methods We conducted a single-center, retrospective, observational study including consecutive patients who underwent ¹³N-ammonia PET between 2013 and 2024. Patients with prior heart transplantation, non-ischemic cardiomyopathy, or unknown HF status were excluded. The primary endpoint was a composite of all-cause death, myocardial infarction, unstable angina, ischemic stroke, heart failure hospitalization, and unplanned revascularization ≥90 days after PET. Patients were stratified by HF status and MFR (cutoff 2.0). Cox regression and restricted cubic spline analyses were performed. Results A total of 675 patients were included (non-HF: n=573; HF: n=102). HF patients had lower stress myocardial blood flow and MFR compared with non-HF patients (both p<0.001).Reduced MFR (<2.0) was associated with higher event rates regardless of HF status (log-rank p<0.001). In multivariable analysis, global MFR was an independent predictor of adverse events, whereas HF status was not. Patients without HF but with reduced MFR had significantly increased risk compared with those without HF and preserved MFR (HR 2.13, p=0.005). The association between reduced MFR and adverse outcomes was consistent across all subgroups, with no significant interactions. Conclusion MFR is reduced in HF patients but retains its prognostic value independent of HF status. Functional assessment of coronary microvascular dysfunction using MFR may provide consistent risk stratification across IHD patients regardless of heart failure status.