bms-747158-02 and Coronary-Artery-Disease

The heart failure epidemic continues to rise with coronary artery disease as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 s), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel

Topics: Animals; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Humans; Myocardial Perfusion Imaging; Organophosphorus Compounds; Positron-Emission Tomography; Predictive Value of Tests; Pyridazines; Radiopharmaceuticals

As the second term of our commitment to Journal begins, we, the editors, would like to reflect on a few topics that have relevance today. These include prognostication and paradigm shifts; Serial testing: How to handle data? Is the change in perfusion predictive of outcome and which one? Ischemia-guided therapy: fractional flow reserve vs perfusion vs myocardial blood flow; positron emission tomography (PET) imaging using Rubidium-82 vs N-13 ammonia vs F-18 Flurpiridaz; How to differentiate microvascular disease from 3-vessel disease by PET? The imaging scene outside the United States, what are the differences and similarities? Radiation exposure; Special issues with the new cameras? Is attenuation correction needed? Are there normal databases and are these specific to each camera system? And finally, hybrid imaging with single-photon emission tomography or PET combined with computed tomography angiography or coronary calcium score. We hope these topics are of interest to our readers.

Topics: Ammonia; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Databases, Factual; Fractional Flow Reserve, Myocardial; Humans; Microcirculation; Multimodal Imaging; Myocardial Ischemia; Myocardial Perfusion Imaging; Nitrogen Radioisotopes; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Predictive Value of Tests; Prognosis; Pyridazines; Rubidium Radioisotopes; Tomography, Emission-Computed, Single-Photon; United States

Rubidium-82 ((82)Rb), the currently commercially available radiotracer for positron emission tomography (PET) myocardial perfusion imaging (MPI), has led to wide availability of PET-MPI for stress-rest imaging. Compared to SPECT MPI, myocardial perfusion PET images have higher spatial and contrast resolution, are less affected by radiotracer scatter, benefit from more precise attenuation correction, and allow dynamic first pass imaging. In addition, PET imaging allows assessment of myocardial function at peak stress and measurement of absolute myocardial blood flow, thus providing critical data not available with SPECT imaging. Further enhancements of the high quality of PET perfusion images may be realized by technologies under development such as respiratory gating, combined respiratory, and ECG gating to generate "motion-frozen" cardiac images, automated patient motion correction software, and high-definition PET, which reduces distortions introduced by the circular geometry of the scanner. Early studies indicate that the experimental PET radiopharmaceutical flurpiridaz F 18 provides high-quality, high-resolution myocardial perfusion images that may enable improved clinical MPI, and has properties well suited to optimized performance by application of these quantitative analytic technologies.

Topics: Coronary Artery Disease; Humans; Image Enhancement; Myocardial Perfusion Imaging; Positron-Emission Tomography; Pyridazines; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

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.. 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.. Clinical myocardial blood flow measurement with

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Female; Fractional Flow Reserve, Myocardial; Humans; Logistic Models; Male; Middle Aged; Myocardial Perfusion Imaging; Positron-Emission Tomography; Predictive Value of Tests; Pyridazines; Reproducibility of Results; Retrospective Studies; Severity of Illness Index

Positron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI.. The primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m. This second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD.. NCT03354273.

Topics: Clinical Trials, Phase III as Topic; Coronary Artery Disease; Humans; Multicenter Studies as Topic; Myocardial Perfusion Imaging; Positron-Emission Tomography; Pyridazines; Research Design

This was a phase II trial to assess flurpiridaz F 18 for safety and compare its diagnostic performance for positron emission tomography (PET) myocardial perfusion imaging (MPI) with Tc-99m single-photon emission computed tomography (SPECT) MPI with regard to image quality, interpretative certainty, defect magnitude, and detection of coronary artery disease (CAD) (≥50% stenosis) on invasive coronary angiography (ICA).. In pre-clinical and phase I studies, flurpiridaz F 18 has shown characteristics of an essentially ideal MPI tracer.. One hundred forty-three patients from 21 centers underwent rest-stress PET and Tc-99m SPECT MPI. Eighty-six patients underwent ICA, and 39 had low-likelihood of CAD. Images were scored by 3 independent, blinded readers.. A higher percentage of images were rated as excellent/good on PET versus SPECT on stress (99.2% vs. 88.5%, p < 0.01) and rest (96.9% vs. 66.4, p < 0.01) images. Diagnostic certainty of interpretation (percentage of cases with definitely abnormal/normal interpretation) was higher for PET versus SPECT (90.8% vs. 70.9%, p < 0.01). In 86 patients who underwent ICA, sensitivity of PET was higher than SPECT (78.8% vs. 61.5%, respectively, p = 0.02). Specificity was not significantly different (PET: 76.5% vs. SPECT: 73.5%). Receiver-operating characteristic curve area was 0.82 ± 0.05 for PET and 0.70 ± 0.06 for SPECT (p = 0.04). Normalcy rate was 89.7% with PET and 97.4% with SPECT (p = NS). In patients with CAD on ICA, the magnitude of reversible defects was greater with PET than SPECT (p = 0.008). Extensive safety assessment revealed that flurpiridaz F 18 was safe in this cohort.. In this phase 2 trial, PET MPI with flurpiridaz F 18 was safe and superior to SPECT MPI for image quality, interpretative certainty, and overall CAD diagnosis.

Topics: Coronary Angiography; Coronary Artery Disease; Coronary Circulation; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Perfusion Imaging; Positron-Emission Tomography; Pyridazines; Radiopharmaceuticals; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon

Topics: Coronary Artery Disease; Fractional Flow Reserve, Myocardial; Humans; Myocardial Perfusion Imaging; Positron-Emission Tomography; Predictive Value of Tests; Pyridazines; Reproducibility of Results; Retrospective Studies