Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined ...by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology—pressure and flow—as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.
Fractional flow reserve (FFR) computation from coronary computed tomography angiography (CTA) datasets (FFRCT) has emerged as a promising noninvasive test to assess hemodynamic severity of coronary ...artery disease (CAD), but has not yet been compared with traditional functional imaging.
The purpose of this study was to evaluate the diagnostic performance of FFRCT and compare it with coronary CTA, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) for ischemia diagnosis.
This subanalysis involved 208 prospectively included patients with suspected stable CAD, who underwent 256-slice coronary CTA, 99mTc-tetrofosmin SPECT, 15OH2O PET, and routine 3-vessel invasive FFR measurements. FFRCT values were retrospectively derived from the coronary CTA images. Images from each modality were interpreted by core laboratories, and their diagnostic performances were compared using invasively measured FFR ≤0.80 as the reference standard.
In total, 505 of 612 (83%) vessels could be evaluated with FFRCT. FFRCT showed a diagnostic accuracy, sensitivity, and specificity of 87%, 90%, and 86% on a per-vessel basis and 78%, 96%, and 63% on a per-patient basis, respectively. Area under the receiver-operating characteristic curve (AUC) for identification of ischemia-causing lesions was significantly greater for FFRCT (0.94 and 0.92) in comparison with coronary CTA (0.83 and 0.81; p < 0.01 for both) and SPECT (0.70 and 0.75; p < 0.01 for both), on a per-vessel and -patient level, respectively. FFRCT also outperformed PET on a per-vessel basis (AUC 0.87; p < 0.01), but not on a per-patient basis (AUC 0.91; p = 0.56). In the intention-to-diagnose analysis, PET showed the highest per-patient and -vessel AUC followed by FFRCT (0.86 vs. 0.83; p = 0.157; and 0.90 vs. 0.79; p = 0.005, respectively).
In this study, FFRCT showed higher diagnostic performance than standard coronary CTA, SPECT, and PET for vessel-specific ischemia, provided coronary CTA images were evaluable by FFRCT, whereas PET had a favorable performance in per-patient and intention-to-diagnose analysis. Still, in patients in whom 3-vessel FFRCT could be analyzed, FFRCT holds clinical potential to provide anatomic and hemodynamic significance of coronary lesions.
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The Adrenergic-Fatty Acid Load in Heart Failure Opie, Lionel H., MD, DPhil, DSc; Knuuti, Juhani, MD, PhD
Journal of the American College of Cardiology,
10/2009, Letnik:
54, Številka:
18
Journal Article
Recenzirano
Odprti dostop
The hypothesis proposed is that heart failure (HF) is associated with a reactive hyperadrenergic state that increases circulating plasma free fatty acids (FFAs), which leads to impaired glucose ...metabolism and insulin resistance. We propose that increased FFA-induced mitochondrial uncoupling and substantial oxygen wastage is closely associated with the generation of reactive oxygen species, inflammatory markers, and the development of insulin resistance. The therapeutic aims of metabolic therapy are as follows: 1) to decrease hyperadrenergic drive; 2) to inhibit lipotoxicity and glucotoxicity; and 3) to increase glucose uptake by muscle. These aims are achieved, respectively, by the following: 1) the use of beta-adrenergic blockade and all measures that relieve the mechanical load on the heart; 2) the use of drugs that inhibit fatty acid oxidation (trimetazidine, perhexiline), although without clinical evidence that the heart is their major site of action in HF; and 3) increase of the transport of glucose into the cells by exercise and metformin. Of these measures, only data concerning the reduction of mortality as the result of exercise are available. Of all the other measures, there are substantial positive data on the use of trimetazidine that demonstrate metabolic and clinical benefit with almost no side effects, but data from a large outcome trial are lacking. Our data suggest a major extracardiac site of trimetazidine action. Ranolazine, which inhibits the late sodium inward current, requires testing in human HF. Insulin to reduce hyperglycemia and FFAs is untested in HF, with incretins such as glucagon-like peptide-1 on the horizon. Other future therapies may include malonyl-coenzyme A regulators to inhibit fatty acid oxidation, fish oil omega-3, and activators of protein kinase C-epsilon.
Fluorine-18 flurpiridaz is a novel positron emission tomography (PET) myocardial perfusion imaging tracer.
This study sought to assess the diagnostic efficacy of flurpiridaz PET versus ...technetium-99m–labeled single photon emission computed tomography SPECT for the detection and evaluation of coronary artery disease (CAD), defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). Flurpiridaz safety was also evaluated.
In this phase III prospective multicenter clinical study, 795 patients with known or suspected CAD from 72 clinical sites in the United States, Canada, and Finland were enrolled. A total of 755 patients were evaluable, and the mean age was 62.3 ± 9.5 years, 31% were women, 55% had body mass index ≥30 kg/m2, and 71% had pharmacological stress. Patients underwent 1-day rest-stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m–labeled SPECT and ICA. Images were read by 3 experts blinded to clinical and ICA data.
Sensitivity of flurpiridaz PET (for detection of ≥50% stenosis by ICA) was 71.9% (95% confidence interval CI: 67.0% to 76.3%), significantly (p < 0.001) higher than SPECT (53.7% 95% CI: 48.5% to 58.8%), while specificity did not meet the prespecified noninferiority criterion (76.2% 95% CI: 71.8% to 80.1% vs. 86.6% 95% CI: 83.2% to 89.8%; p = NS). Receiver-operating characteristic curve analysis demonstrated superior discrimination of CAD by flurpiridaz PET versus SPECT in the overall population, in women, obese patients, and patients undergoing pharmacological stress testing (p < 0.001 for all). Flurpiridaz PET was superior to SPECT for defect size (p < 0.001), image quality (p < 0.001), diagnostic certainty (p < 0.001), and radiation exposure (6.1 ± 0.4 mSv vs. 13.4 ± 3.2 mSv; p < 0.001). Flurpiridaz PET was safe and well tolerated.
Flurpiridaz PET myocardial perfusion imaging shows promise as a new tracer for CAD detection and assessment of women, obese patients, and patients undergoing pharmacological stress testing. A second phase III Food and Drug Administration trial is ongoing. (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710)
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