Review Article

Non-invasive quantification of coronary vascular dysfunction for diagnosis and management of coronary artery disease

The coronary microvasculature is responsible for providing oxygen and nutrients to myocardial tissue. A healthy microvasculature with an intact and properly functioning endothelium accomplishes this by seemless changes in vascular tone to match supply and demand. Perturbations in the normal physiology of the microvasculature, including endothelial and/or vascular smooth muscle dysfunction, result in impaired function (vasoconstriction, antithrombotic, etc.) and structural (hypertrophic, fibrotic) abnormalities that lead to microvascular ischemia and potential organ damage. While coronary microvascular dysfunction (CMD) is the primary pathologic driving force in ischemia with non-obstructive coronary artery disease (INOCA), angina with no obstructive coronary arteries (ANOCA), and myocardial infarction with non-obstructed coronary arteries (MINOCA), it may be a bystander in many cardiac disorders which later become pathologically associated with signs and/or symptoms of myocardial ischemia. Importantly, regardless of the primary or secondary basis of CMD in the heart, it is associated with important increases in morbidity and mortality. In this review we discuss salient features pertaining to known pathophysiologic mechanisms driving CMD, the spectrum of heart diseases where it places a critical role, invasive and non-invasive diagnostic testing, management strategies, and the gaps in knowledge where future research efforts are needed.

Positron emission tomography and/or computed tomography (PET/CT) MPI is a powerful imaging modality for the assessment of cardiovascular diseases. It offers several advantages over single-photon emission computed tomography (SPECT) MPI including robust attenuation correction and absolute quantification of radiotracer activity. PET MPI has a large evidence base and is the only clinical tool to evaluate coronary microvascular dysfunction. In addition, the clinical use and evidence base for 2-deoxy-2-[¹⁸F]fluoro-D-g1ucose (¹⁸F-FDG) cardiac PET imaging for inflammation and metabolism imaging is rising exponentially. In order to gain from the advances of this sophisticated quantitative technique, a high-quality scan is critical. It is important for readers to recognize a poor-quality scan, identify artifacts contributing to the poor image quality, and understand how to correct them prior to reporting the results. In this review, we will discuss some normal variants and pitfalls in cardiac PET/CT radionuclide MPI, myocardial viability, and inflammation imaging.

The aim of this study was to evaluate the incremental prognostic value of global coronary flow reserve (CFR) in patients with known or suspected coronary artery disease who were undergoing stress cardiac magnetic resonance (CMR) imaging.

Coronary microvascular dysfunction results in impaired global CFR and is implicated in the development of both atherosclerosis and heart failure. Although noninvasive assessment of CFR with positron emission tomography provides independent prognostic information, the incremental prognostic value of CMR-derived CFR remains unclear.

Consecutive patients undergoing stress perfusion CMR were prospectively enrolled (n = 507). Coronary sinus flow was measured using phase-contrast imaging at baseline (pre) and immediately after stress (peak) perfusion. CFR was calculated as the ratio of peak to pre-flow. Patients were followed for major adverse cardiac events (MACE): death, nonfatal myocardial infarction, heart failure hospitalization, sustained ventricular tachycardia, and late revascularization. Cox proportional hazards regression modeling was used to examine the association between CFR and MACE. The incremental prognostic value of CFR was assessed in nested models.

Over a median follow-up of 2.1 years, 80 patients experienced MACE. By Kaplan-Meier analysis, the risk of MACE was significantly higher in patients with CFR lower than the median (2.2) (log-rank p < 0.001); this remained significant after adjustment for the presence of ischemia and late gadolinium enhancement (LGE) (log-rank p < 0.001). CFR was significantly associated with the risk of MACE after adjustment for clinical and imaging risk factors, including ischemia extent, ejection fraction, and LGE size (hazard ratio: 1.238; p = 0.018). Addition of CFR in this model resulted in significant improvement in the C-index (from 0.70 to 0.75; p = 0.0087) and a continuous net reclassification improvement of 0.198 (95% confidence interval: 0.120 to 0.288).

CMR-derived CFR is an independent predictor of MACE in patients with known or suspected coronary artery disease, incremental to common clinical and CMR risk factors. These findings suggest a role for CMR-derived CFR in identifying patients at risk of adverse events following stress CMR, even in the absence of ischemia and LGE.