Flow-based phenotypes of coronary microvascular dysfunction and cardiovascular risk
L Seidelin, M Rauf, R Haahr, R S Ripa, M Krakauer, T Holmager, E PrescottAbstract
Background
Coronary microvascular dysfunction (CMD), quantified by reduced myocardial flow reserve (MFR), is a robust predictor of adverse cardiovascular outcomes. Reduced MFR may result from impaired hyperaemic myocardial blood flow (classical CMD) or elevated resting flow (here defined as endogenous CMD), reflecting potentially distinct microvascular phenotypes. Whether these mechanisms carry similar prognostic significance remains unclear.
Purpose
To investigate the prognostic impact of flow-based CMD phenotypes in patients with suspected coronary artery disease referred for clinical 82Rb-PET and to evaluate the prognostic relevance of resting and hyperaemic myocardial blood flow in patients with preserved MFR.
Methods
A multicentre cohort from three Danish centres included patients referred for a clinically indicated 82Rb-PET myocardial perfusion imaging between January 2018 and August 2020 (N=7323), with complete follow-up through nationwide registries. Patients with reversible perfusion defects > 4% were excluded. CMD was defined as MFR < 2.0 and subclassified by resting myocardial blood flow (MBF) into ‘classical CMD’ (≤ 1.2 mL/min/g) and elevated resting-flow CMD’ (>1.2 mL/min/g). Patients with preserved MFR (≥ 2) were characterized as true normal or grey-zone based on resting and hyperaemic MBF. The primary outcome was a composite of myocardial infarction, ischaemic stroke, heart failure, unstable angina, cardiovascular death with follow-up until 14 May 2024. Competing risk and Cox regression models adjusted for age and sex were applied.
Results
A total of 3,223 patients were included. Patients with classical CMD were older, more often male and had a higher burden of risk factors (table). Using true normal patients as reference, classical CMD showed the strongest association with the composite endpoint (subdistribution hazard ratio (SHR) 3.14, 95% CI: 2.50–3.95), with particularly high risks of heart failure (SHR 4.95, 95% CI: 3.42-7.15), cardiovascular death (SHR 6.18, 95% CI: 2.77-13.75), and all-cause death (HR 2.96, 95% CI: 2.15-4.09) (figure 1). CMD driven by elevated resting myocardial blood flow was also independently associated with the composite endpoint, though with lower effect sizes mainly driven by all-cause death (HR 3.04, 95% CI: 2.23-4.16) and cardiovascular death (SHR 3.35, 95% CI: 1.43-7.81). Among patients with preserved MFR, grey-zone abnormalities were associated with modestly increased risk, primarily for heart failure (SHR 1.74, 95% CI: 1.20-2.54) and all-cause death (HR 1.59, 95% CI: 1.16-2.18.
Conclusions
CMD driven by impaired hyperaemic flow carries substantially higher cardiovascular risk than CMD driven by elevated resting flow. Even in patients with preserved MFR, abnormalities in resting or hyperaemic MBF identify subgroups at increased risk.Table1_baselineFigure_cummulative