Positron Emission Tomography Myocardial Perfusion Research Articles

Prognostic value of normal positron emission tomography myocardial perfusion imaging in patients with known or suspected coronary artery disease: a meta-analysis.

Several studies have confirmed high diagnostic performance of positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with known or suspected coronary artery disease. However, whether the superior diagnostic accuracy could translate into improved mortality outcomes remains unknown. The aim of this study was to define the prognostic value of normal PET MPI. PubMed and EMBASE were searched to identify related studies up to June 2016. All studies using PET MPI to evaluate subjects with known or suspected coronary artery disease and providing absolute number of patients with a negative test and primary data on clinical outcomes with a follow-up time ≥3 months were included for analysis. The search yielded 11 studies comprising 20,471 patients for final analysis. The negative-predictive value (NPV) for cardiac death, all-cause death and major adverse cardiovascular events (MACE) were 98.80% [95% confidence interval (CI), 97.64%-99.39%], 94.89% (95% CI: 92.99-96.30%) and 90.26% (95% CI: 78.01-96.03%), over 36.9 months of follow-up for cardiac death, over 26.8 months for all-cause death and 35.7 months for MACE. The corresponding annualized event rates were 0.39%, 2.29% and 3.27%, respectively. In subgroup analyses of different imaging analysis methods for PET MPI, studies using perfusion abnormity had a similar NPV as compared with those using coronary flow reserve (98.46% vs 98.86%, p-value = NS), with a corresponding annualized event rate after negative tests (equal to 1 - NPV) as 0.45% and 0.42%, respectively. Normal PET has a high NPV for cardiac death, MACE and all-cause mortality. Different indexes used for PET imaging analysis have a comparable prognostic value. Advances in knowledge: A normal PET MPI conferred a very low risk of cardiac death of 0.39% per year, which is close to that of a normal aged-matched population.

Effect of methoxy group position on biological properties of 18F–labeled benzyl triphenylphosphonium cations

Introduction18F–labeled phosphonium cations targeting mitochondrial membrane potential would be promising for positron emission tomography (PET) myocardial perfusion imaging (MPI). The purpose of this study was to examine the influence of additional methoxy group and its different positions on myocardium uptake and pharmacokinetics properties of 18F–labeled benzyl triphenylphosphonium cations. MethodIn this study, three novel 18F–labeled phosphonium cations, [18F]4-(fluoromethyl)benzyltris(4-methoxyphenyl) phosphonium cation (1b), [18F]4-(fluoromethyl)benzyltris(2-methoxyphenyl) phosphonium cation (2b) and [18F]4-(fluoromethyl)benzyltris(3-methoxyphenyl) phosphonium cation (3b), were efficiently prepared by a One-Pot method starting from the substitution of non-carried-added fluoride-18. Radiotracers were purified by HPLC. Physicochemical properties, in vitro cell uptake assay, in vivo mice biodistribution and rat micro-PET imaging were investigated. ResultsResults suggested that the position of methoxy group exhibited significant effect on the biological properties of 18F–labeled benzyl triphenylphosphonium cations. The addition of methoxy group on orth- or meta-position of the radiotracers accelerated the radioactivity clearance from liver. The para-radiotracer had the highest uptake in the heart and other non-targeting organs. According to the biodistribution data, 2b (ortho-) displayed the fastest liver clearance and highest heart-to-background ratios. And its rat micro-PET images at 60min post-injection revealed a good visualization of heart and favorable heart-to-background contrast. Nevertheless, 2b exhibited a lower initial liver uptake and quicker liver clearance compared with 99mTc-sestamibi. ConclusionThe ortho- compound (2b) displayed the most favorable biological properties as a potential MPI agent to acquire high contrast images early after injection.

Coronary flow reserve and relative flow reserve measured by N-13 ammonia PET for characterization of coronary artery disease.

We evaluated the relationships between coronary flow reserve (CFR) and relative flow reserve (RFR) measured by N-13 ammonia positron emission tomography (PET) for characterization of epicardial coronary artery disease (CAD). Sixty-nine consecutive stable angina patients underwent N-13 ammonia PET, coronary computed tomography angiography (CCTA), and if necessary, invasive coronary angiography (CAG) within 2weeks. Myocardial blood flow (MBF), CFR, RFR, and coronary vascular resistance of the reference arterial territory (CVRref) were measured by N-13 ammonia PET. The presence of significant stenosis (SS) and diffuse atherosclerosis (DA) was evaluated on CCTA and CAG. Functional parameters measured by PET were compared among arteries with and without SS and DA. Arteries with SS and those with DA showed significantly lower stress MBF, as compared to those without. RFR was significantly lower in arteries with SS as compared to those without, while CFR was not. CFR was significantly lower in arteries with DA as compared to those without, while RFR was not. Among arteries without SS, CFR was significantly lower in those with DA as compared to those without. However, among arteries with SS, CFR was similar between those with and without DA. In contrast, RFR was significantly lower in arteries with SS, regardless of the presence of DA. CFR and RFR showed a weak positive correlation (r=0.269) with discordance in 24 cases (35%). Among the arteries with CFR-RFR discordance, the prevalence of DA was significantly higher in those with low CFR but preserved RFR, as compared to those with preserved CFR but low RFR (75 vs 25%, p=0.028). CVRref was significantly higher in arteries with DA, implicating a correlation of DA with underlying microvascular disease. CFR and RFR measured by myocardial perfusion PET could provide a comprehensive information for characterization of epicardial CAD.

Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease.

Cardiovascular disease (CVD) fatality rates are higher for women than for men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary flow reserve (CFR), an integrated measure of large- and small-vessel CAD and myocardial ischemia, identifies patients at risk for CVD death, but is not routinely measured in clinical practice. We sought to investigate the impact of sex, CFR, and angiographic CAD severity on adverse cardiovascular events. Consecutive patients (n=329, 43% women) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography and with left ventricular ejection fraction >40% were followed (median, 3.0 years) for a composite end point of major adverse cardiovascular events, including cardiovascular death and hospitalization for nonfatal myocardial infarction or heart failure. The extent and severity of angiographic CAD were estimated by using the CAD prognostic index, and CFR was quantified by using positron emission tomography. Although women in comparison with men had lower pretest clinical scores, rates of prior myocardial infarction, and burden of angiographic CAD (P<0.001), they demonstrated greater risk of CVD events, even after adjustment for traditional risk factors, imaging findings, and early revascularization (adjusted hazard ratio, 2.05; 95% confidence interval, 1.05-4.02; P=0.03). Impaired CFR was similarly present among women and men, but in patients with low CFR (<1.6, n=163), women showed a higher frequency of nonobstructive CAD, whereas men showed a higher frequency of severely obstructive CAD (P=0.002). After also adjusting for CFR, the effect of sex on outcomes was no longer significant. When stratified by sex and CFR, only women with severely impaired CFR demonstrated significantly increased adjusted risk of CVD events (P<0.0001, P for interaction=0.04). Women referred for coronary angiography had a significantly lower burden of obstructive CAD in comparison with men but were not protected from CVD events. Excess cardiovascular risk in women was independently associated with impaired CFR, representing a hidden biological risk, and a phenotype less amenable to revascularization. Impaired CFR, particularly absent severely obstructive CAD, may represent a novel target for CVD risk reduction.

Fused cardiac hybrid imaging with coronary computed tomography angiography and positron emission tomography in patients with complex coronary artery anomalies.

To provide data on the value of fused cardiac hybrid imaging with coronary computed tomography angiography (CCTA) and positron emission tomography myocardial perfusion imaging (PET-MPI) in patients with complex coronary artery anomalies (CCAA). This is a retrospective, single-center study. Seven consecutive patients with CCAA (mean 57±7y, 86% were male) who underwent clinically indicated hybrid CCTA/PET-MPI between 2005 and 2015 in our clinic were included. The findings from both modalities and fused cardiac hybrid imaging were evaluated in these patients. Out of the seven patients with CCAA, two patients had Bland-White-Garland anomaly, two patients showed a coronary artery fistula, two patients showed a "single right," and one patient showed a "single left" coronary artery. Semiquantitative fused hybrid CCTA/PET-MPI depicted inferolateral scar matching the territory of a nonanomalous vessel with significant concomitant coronary artery disease (CAD) in one patient only. In contrast, analysis of quantitative myocardial blood flow (MBF) as assessed by fused hybrid CCTA/PET-MPI revealed abnormally reduced flow capacities in the territories subtended by the anomalous vessels in 4 patients. In this case series of middle-aged patients with CCAA, perfusion defects as assessed by semiquantitative PET-MPI were rare and attributable to concomitant CAD rather than to the anomalous vessel itself. By contrast, impaired MBF as assessed by quantitative hybrid CCTA/PET-MPI was revealed in the majority of patients in the vessel territories subtended by the anomalous coronary artery itself. Fused hybrid CCTA/PET-MPI incorporating information on morphology and on semiquantitative and quantitative myocardial perfusions may provide added value for the management of patients with CCAA.

Recent Advances in Nuclear Cardiology.

Nuclear cardiology is one of the major fields of nuclear medicine practice. Myocardial perfusion studies using single-photon emission computed tomography (SPECT) have played a crucial role in the management of coronary artery diseases. Positron emission tomography (PET) has also been considered an important tool for the assessment of myocardial viability and perfusion. However, the recent development of computed tomography (CT)/magnetic resonance imaging (MRI) technologies and growing concerns about the radiation exposure of patients remain serious challenges for nuclear cardiology. In response to these challenges, remarkable achievements and improvements are currently in progress in the field of myocardial perfusion imaging regarding the applicable software and hardware. Additionally, myocardial perfusion positron emission tomography (PET) is receiving increasing attention owing to its unique capability of absolute myocardial blood flow estimation. An F-18-labeled perfusion agent for PET is under clinical trial with promising interim results. The applications of F-18 fluorodeoxyglucose (FDG) and F-18 sodium fluoride (NaF) to cardiovascular diseases have revealed details on the basic pathophysiology of ischemic heart diseases. PET/MRI seems to be particularly promising for nuclear cardiology in the future. Restrictive diseases, such as cardiac sarcoidosis and amyloidosis, are effectively evaluated using a variety of nuclear imaging tools. Considering these advances, the current challenges of nuclear cardiology will become opportunities if more collaborative efforts are devoted to this exciting field of nuclear medicine.

Synthesis and Evaluation of [(18) F]-Ammonium BODIPY Dyes as Potential Positron Emission Tomography Agents for Myocardial Perfusion Imaging.

Recently, we demonstrated the potential of a [(18) F]-trimethylammonium BODIPY dye for cardiac imaging. This is the first example of the use of the [(18) F]-ammonium BODIPY dye for positron emission tomography (PET) myocardial perfusion imaging (MPI). In this report, we extend our study to other ammonium BODIPY dyes with different nitrogen substituents. These novel ammonium BODIPY dyes were successfully prepared and radiolabeled by the SnCl4 -assisted (18) F-(19) F isotopic exchange method. The microPET results and the biodistribution data reveal that nitrogen substituent changes have a significant effect on the in vivo and pharmacological properties of the tracers. Of the novel [(18) F]-ammonium BODIPY dyes prepared in this work, the [(18) F]-dimethylethylammonium BODIPY is superior in terms of myocardium uptake and PET imaging contrast. These results support our hypothesis that the ammonium BODIPY dyes have a great potential for use as PET/optical dual-modality MPI probes.

Integration of Quantitative Positron Emission Tomography Absolute Myocardial Blood Flow Measurements in the Clinical Management of Coronary Artery Disease.

In the >40 years since planar myocardial imaging with(43)K-potassium was introduced into clinical research and management of patients with coronary artery disease (CAD), diagnosis and treatment have undergone profound scientific and technological changes. One such innovation is the current state-of-the-art hardware and software for positron emission tomography myocardial perfusion imaging, which has advanced it from a strictly research-oriented modality to a clinically valuable tool. This review traces the evolving role of quantitative positron emission tomography measurements of myocardial blood flow in the evaluation and management of patients with CAD. It presents methodology, currently or soon to be available, that offers a paradigm shift in CAD management. Heretofore, radionuclide myocardial perfusion imaging has been primarily qualitative or at best semiquantitative in nature, assessing regional perfusion in relative terms. Thus, unlike so many facets of modern cardiovascular practice and CAD management, which depend, for example, on absolute values of key parameters such as arterial and left ventricular pressures, serum lipoprotein, and other biomarker levels, the absolute levels of rest and maximal myocardial blood flow have yet to be incorporated into routine clinical practice even in most positron emission tomography centers where the potential to do so exists. Accordingly, this review focuses on potential value added for improving clinical CAD practice by measuring the absolute level of rest and maximal myocardial blood flow. Physiological principles and imaging fundamentals necessary to understand how positron emission tomography makes robust, quantitative measurements of myocardial blood flow possible are highlighted.

Two-Dimensional Speckle-Tracking during Dobutamine Stress Echocardiography in the Detection of Myocardial Ischemia in Patients with Suspected Coronary Artery Disease

Two-dimensional speckle-tracking applied to dobutamine stress echocardiography (DSE) may aid in the detection of coronary artery disease (CAD). The aim of this study was to determine the value of strain, strain rate, and postsystolic strain index (PSI) measured by speckle-tracking during DSE in the evaluation of the presence, extent, and severity of myocardial ischemia. Fifty patients 63±7years of age with intermediate probability of CAD were prospectively recruited. All patients underwent DSE, quantitative positron emission tomographic perfusion imaging, and invasive angiography. Regional peak systolic longitudinal strain, strain rate, and PSI were measured at rest, at a dobutamine dose of 20μg/kg/min, at peak stress, and at early recovery (1min after stress). Obstructive CAD was defined as >75% stenosis or 40% to 75% stenosis combined with either fractional flow reserve<0.80 or abnormal findings on myocardial perfusion positron emission tomography. Obstructive CAD was detected in 22 patients and in 36 of 150 coronary arteries. Strain analyses showed the highest reproducibility at rest, at a dobutamine dose of 20μg/kg/min, and at early recovery. Increased PSI and reduced strain during early recovery were the strongest predictors of obstructive CAD and were associated with the extent, localization, and depth of myocardial ischemia by positron emission tomography. On vessel-based analysis, strain, PSI, and visual analysis of wall motion provided comparable diagnostic accuracy, whereas the combination of strain or PSI with visual analysis provided incremental value over visual analysis alone. Assessment of systolic or postsystolic strain by speckle-tracking echocardiography during early recovery after DSE can help in the detection of hemodynamically significant coronary stenosis compared with visual wall motion analysis alone.

Flow-Based Functional Assessment of Coronary Artery Disease by Myocardial Perfusion Positron Emission Tomography in the Era of Fractional Flow Reserve

Myocardial perfusion positron emission tomography (PET) has long been regarded as a gold standard of myocardial blood flow (MBF) measurement. However, since randomized clinical trials showed the prognostic value of fractional flow reserve (FFR)-guided revascularization, FFR has rapidly become a new gold standard of functionally significant coronary artery disease (CAD). Despite the predominance of FFR in the management of stable CAD, FFR also has limitations. Overcoming hurdles by the lesion-specific MBF measurement by hybrid imaging and novel flow parameter can be a complimentary tool.

Flow-Based Functional Assessment of Coronary Artery Disease by Myocardial Perfusion Positron Emission Tomography in the Era of Fractional Flow Reserve

Flow-Based Functional Assessment of Coronary Artery Disease by Myocardial Perfusion Positron Emission Tomography in the Era of Fractional Flow Reserve

Feasibility and diagnostic accuracy of exercise treadmill nitrogen-13 ammonia PET myocardial perfusion imaging of obese patients

BackgroundTreadmill exercise nitrogen-13 (13N)-ammonia positron emission tomography (PET) has logistical challenges and limited literature. We aimed to assess its feasibility, image quality, and diagnostic accuracy in obese and nonobese patients. Methods and ResultsBetween 2009 and 2012, 10,804 patients were referred for myocardial perfusion imaging, including 300 for treadmill PET, of whom 265 were included in this study. Treadmill testing and PET were performed using standard procedures. Image quality, perfusion, and summed stress score (SSS) were assessed. Invasive coronary angiography was performed within 90 days of PET in 43 patients. Mean ± SD body mass index (BMI) was 35.7 ± 7.7 kg/m2 (range 19.5-63.5 kg/m2). Feasibility of treadmill 13N-ammonia PET was 100%. Exercise duration was less for obese patients than nonobese patients (P < .001). Image quality was rated good for 96.9% of obese and 100% of nonobese patients. For all patients, sensitivity was 86.4% and specificity was 74.4%. Diagnostic accuracy did not change significantly with increasing BMI. SSS remained significant in predicting angiographic coronary artery disease after adjustment for age, sex, and Duke treadmill score. ConclusionsTreadmill 13N-ammonia PET is highly feasible, yields good image quality, and has moderately high diagnostic accuracy in a small subset of obese and nonobese patients who are deemed able to perform treadmill exercise.

Prognostic Value of Coronary Flow Reserve in Patients with Dialysis-Dependent ESRD

Capillary rarefaction of the coronary microcirculation is a consistent phenotype in patients with dialysis-dependent ESRD (dd-ESRD) and may help explain their excess mortality. Global coronary flow reserve (CFR) assessed by positron emission tomography (PET) is a noninvasive, quantitative marker of myocardial perfusion and ischemia that integrates the hemodynamic effects of epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. We tested whether global CFR provides risk stratification in patients with dd-ESRD. Consecutive patients with dd-ESRD clinically referred for myocardial perfusion PET imaging were retrospectively included, excluding patients with prior renal transplantation. Per-patient CFR was calculated as the ratio of stress to rest absolute myocardial blood flow. Multivariable Cox proportional hazards models, including age, overt cardiovascular disease, and myocardial scar/ischemia burden, were used to assess the independent association of global CFR with all-cause and cardiovascular mortality. The incremental value of global CFR was assessed with relative integrated discrimination index and net reclassification improvement. In 168 patients included, median global CFR was 1.4 (interquartile range, 1.2-1.8). During follow-up (median of 3 years), 36 patients died, including 21 cardiovascular deaths. Log-transformed global CFR independently associated with all-cause mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.14; P<0.001) and cardiovascular mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.15; P=0.002). For all-cause mortality, addition of global CFR resulted in risk reclassification in 27% of patients. Thus, global CFR may provide independent and incremental risk stratification for all-cause and cardiovascular mortality in patients with dd-ESRD.

Impact of time-of-flight on qualitative and quantitative analyses of myocardial perfusion PET studies using 13N-ammonia

BackgroundThe impact of time-of-flight (TOF) in myocardial perfusion 13N-ammonia positron emission tomography (PET) is unclear. Methods and ResultsTwenty consecutive subjects underwent rest and adenosine stress 13N-ammonia myocardial perfusion PET. Two sets of images were reconstructed using TOF-ordered subset expectation maximization (TOF-OSEM) and 3-dimensional row-action maximum likelihood algorithm (3D-RAMLA). Qualitative and quantitative analyses from the TOF-OSEM and 3D-RAMLA reconstructions were compared. Count profile curves revealed that TOF relatively increased the uptake of 13N-ammonia at the lateral walls, and apical thinning was emphasized on the TOF images. Both segmental rest and stress myocardial blood flow (MBF) values were higher with TOF-OSEM use than with 3D-RAMLA use (rest MBF: 0.955 ± 0.201 vs 0.836 ± 0.185, P < .001; stress MBF: 2.149 ± 0.697 vs 2.058 ± 0.721, P < .001). The differentiation of MBF between reconstructions was more enhanced under rest conditions. Thus, segmental myocardial flow reserve (MFR) observed using TOF-OSEM reconstruction was lower than that observed using 3D-RAMLA (2.25 ± 0.57 vs 2.46 ± 0.75, P < .001). No remarkable differences were observed between segmental and territorial results. ConclusionsTOF increased lateral wall counts and emphasized apical thinning. Quantitatively, TOF reconstruction showed increased MBF, especially under relatively low perfusion conditions.

Cardiac applications of PET

Routine use of cardiac positron emission tomography (PET) applications has been increasing but has not replaced cardiac single-photon emission computerized tomography (SPECT) studies yet. The majority of cardiac PET tracers, with the exception of fluorine-18 fluorodeoxyglucose (18F-FDG), are not widely available, as they require either an onsite cyclotron or a costly generator for their production. 18F-FDG PET imaging has high sensitivity for the detection of hibernating/viable myocardium and has replaced Tl-201 SPECT imaging in centers equipped with a PET/CT camera. PET myocardial perfusion imaging with various tracers such as Rb-82, N-13 ammonia, and O-15 H2O has higher sensitivity and specificity than myocardial perfusion SPECT for the detection of coronary artery disease (CAD). In particular, quantitative PET measurements of myocardial perfusion help identify subclinical coronary stenosis, better define the extent and severity of CAD, and detect ischemia when there is balanced reduction in myocardial perfusion due to three-vessel or main stem CAD. Fusion images of PET perfusion and CT coronary artery calcium scoring or CT coronary angiography provide additional complementary information and improve the detection of CAD. PET studies with novel 18F-labeled perfusion tracers such as 18F-flurpiridaz and 18F-FBnTP have yielded high sensitivity and specificity in the diagnosis of CAD. These tracers are still being tested in humans, and, if approved for clinical use, they will be commercially and widely available. In addition to viability studies, 18F-FDG PET can also be utilized to detect inflammation/infection in various conditions such as endocarditis, sarcoidosis, and atherosclerosis. Some recent series have obtained encouraging results for the detection of endocarditis in patients with intracardiac devices and prosthetic valves. PET tracers for cardiac neuronal imaging, such as C-11 HED, help assess the severity of heart failure and post-transplant cardiac reinnervation, and understand the pathogenesis of arrhytmias. The other uncommon applications of cardiac PET include NaF imaging to identify calcium deposition in atherosclerotic plaques and β-amyloid imaging to diagnose cardiac amyloid involvement. 18F-FDG imaging with a novel PET/MR camera has been reported to be very sensitive and specific for the differentiation between malignant and nonmalignant cardiac masses. The other potential applications of PET/MR are cardiac infectious/inflammatory conditions such as endocarditis.

Doppler-derived intracoronary physiology indices predict the occurrence of microvascular injury and microvascular perfusion deficits after angiographically successful primary percutaneous coronary intervention.

A total of 40% to 50% of patients with ST-segment-elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). Sixty patients with ST-segment-elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure-flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure-velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H2 (15)O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H2 (15)O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure-velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04). Doppler-flow-derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow. http://www.trialregister.nl. Unique identifier: NTR3164.

Clinical utility of inappropriate positron emission tomography myocardial perfusion imaging: Test results and cardiovascular events

BackgroundAppropriate use criteria for myocardial perfusion imaging (MPI) were developed to categorize scenarios where MPI might be beneficial (appropriate) or not (inappropriate). Few investigations have evaluated the clinical utility of this categorization strategy, particularly with positron emission tomography (PET) MPI. Methods and ResultsWe conducted this retrospective cohort investigation in a Veterans Affairs (VA) medical center, on predominantly male subjects who underwent PET-MPI. We correlated appropriateness to test result and cardiovascular events. Of 521 subjects, 414 (79.5%) were appropriate, 54 (10.4%) were uncertain, and 53 (10.2%) were inappropriate. PET-MPI was abnormal more often when appropriate or uncertain (28% and 34.6%, respectively, vs 7.7% for inappropriate, P = .003). Among abnormal inappropriate tests, none detected occult ischemia. By Cox regression, summed difference score ≥5 (HR 5.06, 95% CI 2.72-9.44) and an abnormal test result (HR 4.48, 95% CI 2.19-9.14) were associated with higher likelihood of catheterization. Log-rank analysis demonstrated similar likelihood of catheterization when comparing abnormal vs normal test result (P < .0001) and between appropriate, uncertain, and inappropriate tests (P = .024). ConclusionsInappropriate PET-MPI was rarely abnormal, associated with low catheterization rates, and failed to detect occult ischemia for any subjects. The clinical utility of inappropriate PET-MPI is negligible.

Positron-Emitting Myocardial Blood Flow Tracers and Clinical Potential

Positron-emitting myocardial flow radiotracers such as 15O-water, 13N-ammonia and 82Rubidium in conjunction with positron-emission-tomography (PET) are increasingly applied in clinical routine for coronary artery disease (CAD) detection, yielding high diagnostic accuracy, while providing valuable information on cardiovascular (CV) outcome. Owing to a cyclotron dependency of 15O-water and 13N-ammonia, their clinical use for PET myocardial perfusion imaging is limited to a few centers. This limitation could be overcome by the increasing use of 82Rubidium as it can be eluted from a commercially available 82Strontium generator and, thus, is independent of a nearby cyclotron. Another novel F-18-labeled myocardial flow radiotracer is flurpiridaz which has attracted increasing interest due to its excellent radiotracer characteristics for perfusion and flow imaging with PET. In particular, the relatively long half-life of 109minutes of flurpiridaz may afford a general application of this radiotracer for PET perfusion imaging comparable to technetium-99m-labeled single-photon emission computed tomography (SPECT). The ability of PET in conjunction with several radiotracers to assess myocardial blood flow (MBF) in ml/g/min at rest and during vasomotor stress has contributed to unravel pathophysiological mechanisms underlying coronary artery disease (CAD), to improve the detection and characterization of CAD burden in multivessel disease, and to provide incremental prognostic information in individuals with subclinical and clinically-manifest CAD. The concurrent evaluation of myocardial perfusion and MBF may lead to a new era of a personalized, image-guided therapy approach that may offer potential to further improve clinical outcome in CV disease patients but needing validation in large-scale clinical trials.

Prognostic value of positron emission tomography myocardial perfusion imaging beyond traditional cardiovascular risk factors: Systematic review and meta-analysis

BackgroundDespite substantive growth in utilization of positron emission tomography (PET) myocardial perfusion imaging (MPI), evidence on its prognostic value is limited. We aimed to comprehensively evaluate the prognostic literature of PET perfusion measures according to the most recent American Heart Association recommendations for assessment of novel cardiovascular biomarkers. MethodsWe searched the literature for studies reporting associations of PET MPI measures and outcomes in patients with known or suspected coronary artery disease. We documented hazard ratios (HR) and 95% confidence intervals (CI) of association effects and quantitatively synthesized them with random-effects meta-analyses. Discrimination, calibration and risk reclassification after addition of PET MPI measures to standard prognostic models were documented. ResultsWe identified 20 eligible studies with median n=551 patients. In meta-analyses, the extents of ischemic and scarred myocardium were significantly associated with cardiac death. Meta-analyses of multivariate estimates for abnormal summed stress score ≥4 and myocardial perfusion reserve <2 revealed significant associations with major adverse cardiovascular events [HR (95% CI) 2.30 (1.53–3.44) and 2.11 (1.33–3.36), respectively]. Changes in model discrimination, calibration or risk reclassification were reported in 5 studies (8 prognostic evaluations). There were marginal improvements in discrimination based on C index and no improvements in model calibration. Net reclassification index ranged from 9.8% to 14.2% and risk classification was significantly improved in 4/5 prognostic evaluations. ConclusionsPET MPI measures were strongly associated with adverse patient outcomes. Risk classification was more consistently improved than discrimination and calibration after addition of PET MPI measures, but reporting of such metrics was overall limited.

Interaction of impaired coronary flow reserve and cardiomyocyte injury on adverse cardiovascular outcomes in patients without overt coronary artery disease.

Minimally elevated serum cardiac troponin reflects myocardial injury and is associated with increased mortality, even absent coronary artery disease (CAD). We sought to investigate the relationship between low-level troponin elevation and impaired coronary flow reserve (CFR), an integrated measure of coronary vasomotor function, and to assess their contributions to adverse outcomes in patients without overt CAD. Consecutive patients (n=761) undergoing evaluation for suspected CAD with troponin before stress myocardial perfusion positron emission tomography were followed up (median, 2.8 years) for major adverse cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, or late revascularization. Patients with flow-limiting CAD, left ventricular ejection fraction <40%, or revascularization within 60 days of imaging were excluded. CFR was quantified from stress/rest myocardial blood flow with the use of positron emission tomography. Compared with patients with negative troponin, those with at least 1 positive troponin (n=97) had higher pretest clinical scores, more renal dysfunction, and lower left ventricular ejection fraction and CFR. In adjusted analysis, impaired CFR remained independently associated with positive troponin (odds ratio, 2.18; 95% confidence interval, 1.37-3.47; P=0.001), and both impaired CFR and positive troponin were independently associated with major adverse cardiovascular events (hazard ratio, 2.25; 95% confidence interval, 1.31-3.86; P=0.003; and hazard ratio, 2.42; 95% confidence interval, 1.34-4.40; P=0.004, respectively). Impaired CFR and positive troponin identified patients at highest risk of major adverse cardiovascular events (log-rank P<0.0001), with a significant interaction (P<0.007) seen between CFR and troponin. In patients without overt CAD, impaired CFR was independently associated with minimally elevated troponin and major adverse cardiovascular events. Impaired CFR, here reflecting microvascular dysfunction, modified the effect of a positive troponin on adverse outcomes.