Added value of myocardial blood flow using 18F-flurpiridaz PET to diagnose coronary artery disease: The flurpiridaz 301 trial.

BACKGROUND: 18F-Flurpiridaz is a promising investigational radiotracer for PET myocardial perfusion imaging with favorable properties for quantification of myocardial blood flow (MBF). We sought to validate the incremental diagnostic value of absolute MBF quantification in a large multicenter trial against quantitative coronary angiography. METHODS: We retrospectively analyzed a subset of patients (N = 231) from the first phase 3 flurpiridaz trial (NCT01347710). Dynamic PET data at rest and pharmacologic stress were fit to a previously validated 2-tissue-compartment model. Absolute MBF and myocardial flow reserve (MFR) were compared with coronary artery disease severity quantified by invasive coronary angiography on a per-patient and per-vessel basis. RESULTS: Stress MBF per-vessel accurately identified obstructive disease (c-index 0.79) and progressively declined with increasing stenosis severity (2.35 ± 0.71 in patients without CAD; 1.92 ± 0.49 in non-obstructed territories of CAD patients; and 1.54 ± 0.50 in diseased territories, P < 0.05). MFR similarly declined with increasing stenosis severity (3.03 ± 0.94; 2.69 ± 0.95; and 2.33 ± 0.86, respectively, P < 0.05). In multivariable logistic regression modeling, stress MBF and MFR provided incremental diagnostic value beyond patient characteristics and relative perfusion analysis. CONCLUSIONS: Clinical myocardial blood flow measurement with 18F-flurpiridaz cardiac PET shows promise for routine application.

Absolute coronary blood flow measurement and microvascular resistance in ST-elevation myocardial infarction in the acute and subacute phase.

BACKGROUND/PURPOSE: In a number of patients with acute myocardial infarction (AMI), myocardial hypoperfusion, known as the no-reflow phenomenon, persists after primary percutaneous intervention (PPCI). The aim of this study was to evaluate the feasibility and safety of a new quantitative method of measuring absolute blood flow and resistance within the perfusion bed of an infarct-related artery. Furthermore, we sought to study no-reflow by correlating these measurements to the index of microvascular resistance (IMR) and the area at risk (AR) as determined by cardiac magnetic resonance imaging (CMR). METHODS: Measurements of absolute flow and myocardial resistance were performed in 20 patients with ST-segment elevation myocardial infarction (STEMI), first immediately following PPCI and then again after 3-5days. These measurements used the technique of thermodilution during a continuous infusion of saline. Flow was expressed in ml/min per gram of tissue within the area at risk. RESULTS: The average time needed for measurement of absolute flow, resistance and IMR was 20min, and all measurements could be performed without complication. A higher flow supplying the AR correlated with a lower IMR in the acute phase. Absolute flow increased from 3.14 to 3.68ml/min/g (p=0.25) and absolute resistance decreased from 1317 to 1099 dyne.sec.cm-5/g (p=0.40) between the first day and fifth day after STEMI. CONCLUSIONS: Measurement of absolute flow and microvascular resistance is safe and feasible in STEMI patients and may allow for a better understanding of microvascular (dys)function in the early phase of AMI.

Regadenoson versus dipyridamole hyperemia for cardiac PET imaging.

OBJECTIVES: The goal of this study was to compare regadenoson and dipyridamole hyperemia for quantitative myocardial perfusion imaging. BACKGROUND: Regadenoson is commonly used for stress perfusion imaging. However, no study in nuclear cardiology has employed a paired design to compare quantitative hyperemic flow from regadenoson to more traditional agents such as dipyridamole. Additionally, the timing of regadenoson bolus relative to tracer administration can be expected to affect quantitative flow. METHODS: Subjects underwent 2 rest/stress cardiac positron emission tomography scans using an Rb-82 generator. Each scan employed dipyridamole and a second drug in random sequence, either regadenoson according to 5 timing sequences or repeated dipyridamole. A validated retention model quantified absolute flow and coronary flow reserve. RESULTS: A total of 176 pairs compared regadenoson (126 pairs, split unevenly among 5 timing sequences) or repeated dipyridamole (50 pairs). The cohort largely had few symptoms, only risk factors, and nearly normal relative uptake images, with 8% typical angina or dyspnea, 20% manifest coronary artery disease, and a minimum quadrant average of 80% (interquartile range: 76% to 83%) on dipyridamole scans. Hyperemic flow varied among regadenoson timing sequences but showed consistently lower stress flow and coronary flow reserve compared with dipyridamole. A timing sequence most similar to the regadenoson package insert achieved about 80% of dipyridamole hyperemia, whereas further delaying radiotracer injection reached approximately 90% of dipyridamole hyperemia. Because of the small numbers of pairs for each regadenoson timing protocol and a paucity of moderate or large perfusion defects, we did not observe a difference in relative uptake. CONCLUSIONS: With the standard timing protocol from the package insert, regadenoson achieved only 80% of dipyridamole hyperemia quantitatively imaged by cardiac positron emission tomography using Rb-82. A nonstandard protocol using a more delayed radionuclide injection after the regadenoson bolus improved its effect to 90% of dipyridamole hyperemia.