Chest pain in patients without obstructive coronary artery disease has been realized as a frequent problem encountered in clinical practice. Invasive flow investigations have suggested that up to two-thirds of patients with nonobstructive coronary atherosclerosis may have microvascular dysfunction (MVD). Positron emission tomography myocardial perfusion imaging in conjunction with tracer-kinetic modeling enables the concurrent quantification of myocardial blood flow (MBF) in milliliters per minute per gram of tissue. This allows the assessment of hyperemic MBFs and myocardial flow reserve for the noninvasive identification and characterization of MVD as an important functional substrate for angina symptoms amenable to intensified and individualized medical intervention with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, and/or angiotensin II type 1 receptor blockers. Recent investigations suggest that cardiac magnetic resonance and computed tomography may also be suitable for the noninvasive detection of MVD. Whether intensified and individualized treatment related improvement or even normalization of hyperemic MBF and/or myocardial flow reserve may lead to a persistent reduction in angina symptoms and/or improved cardiovascular outcome as compared to standard care, deserves further testing in large-scale randomized clinical trials.

https://imaging.onlinejacc.org/content/jimg/early/2019/04/10/j.jcmg.2018.11.036.full.pdf

Coronary Microvascular Dysfunction: Clinical Considerations and Noninvasive Diagnosis

Radionuclide myocardial perfusion imaging (MPI) is among the most commonly performed diagnostic tests in cardiology. Although the diagnostic and prognostic applications of radionuclide MPI are supported by a wealth of observational and clinical trial data, its performance is limited by two

https://jnm.snmjournals.org/content/jnumed/59/2/273.full.pdf

Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC.

Background:It is suggested that the integration of maximal myocardial blood flow (MBF) and coronary flow reserve (CFR), termed coronary flow capacity, allows for comprehensive evaluation of patient...

Integrated Noninvasive Physiological Assessment of Coronary Circulatory Function and Impact on Cardiovascular Mortality in Patients With Stable Coronary Artery Disease

We assessed the feasibility of myocardial blood flow (MBF) and flow reserve (MFR) estimation using dynamic SPECT with a novel CZT camera in patients with stable CAD, in comparison with 15O–water PET and fractional flow reserve (FFR). Thirty patients were prospectively included and underwent FFR measurements in the main coronary arteries (LAD, LCx, RCA). A stenosis ≥50% was considered obstructive and a FFR abnormal if ≤0.8. All patients underwent a dynamic rest/stress 99mTc-sestamibi CZT-SPECT and 15O–water PET for MBF and MFR calculation. Net retention kinetic modeling was applied to SPECT data to estimate global uptake values, and MBF was derived using Leppo correction. Ischemia by PET and CZT-SPECT was considered present if MFR was lower than 2 and 2.1, respectively. CZT-SPECT yielded higher stress and rest MBF compared to PET for global and LAD and LCx territories, but not in RCA territory. MFR was similar in global and each vessel territory for both modalities. The sensitivity, specificity, accuracy, positive and negative predictive value of CZT-SPECT were, respectively, 83.3, 95.8, 93.3, 100 and 85.7% for the detection of ischemia and 58.3, 84.6, 81.1, 36.8 and 93% for the detection of hemodynamically significant stenosis (FFR ≤ 0.8). Dynamic 99mTc-sestamibi CZT-SPECT was technically feasible and provided similar MFR compared to 15O–water PET and high diagnostic value for detecting impaired MFR and abnormal FFR in patients with stable CAD.

/pdf/first-validation-of-myocardial-flow-reserve-assessed-by-3edujbjvw5.pdf

First validation of myocardial flow reserve assessed by dynamic 99mTc-sestamibi CZT-SPECT camera: head to head comparison with 15O-water PET and fractional flow reserve in patients with suspected coronary artery disease. The WATERDAY study

Cardiac PET perfusion tracers: current status and future directions.

Myocardial perfusion imaging has limited sensitivity for the detection of high-risk coronary artery disease (CAD). We tested the hypothesis that a normal coronary flow reserve (CFR) would be helpful for excluding the presence of high-risk CAD on angiography. Methods: We studied 290 consecutive patients undergoing 82Rb PET within 180 d of invasive coronary angiography. High-risk CAD on angiography was defined as 2-vessel disease (≥70% stenosis), including the proximal left anterior descending artery; 3-vessel disease; or left main CAD (≥50% stenosis). Patients with prior Q wave myocardial infarction, elevated troponin levels between studies, prior coronary artery bypass grafting, a left ventricular ejection fraction of less than 40%, or severe valvular heart disease were excluded. Results: Fifty-five patients (19%) had high-risk CAD on angiography. As expected, the trade-off between the sensitivity and the specificity of the CFR for identifying high-risk CAD varied substantially depending on the cutoff selected. In multivariable analysis, a binary CFR of less than or equal to 1.93 provided incremental diagnostic information for the identification of high-risk CAD beyond the model with the Duke clinical risk score (>25%), percentage of left ventricular ischemia (>10%), transient ischemic dilation index (>1.07), and change in the left ventricular ejection fraction during stress ( 1.93) excluded high-risk CAD with a high sensitivity (86%) and a high negative predictive value (97%). Conclusion: A normal CFR has a high negative predictive value for excluding high-risk CAD on angiography. Although an abnormal CFR increases the probability of significant obstructive CAD, it cannot reliably distinguish significant epicardial stenosis from nonobstructive, diffuse atherosclerosis or microvascular dysfunction.

https://jnm.snmjournals.org/content/jnumed/55/2/248.full.pdf

Preserved Coronary Flow Reserve Effectively Excludes High-Risk Coronary Artery Disease on Angiography

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Preserved Coronary Flow Reserve Effectively Excludes High-Risk Coronary Artery Disease on Angiography