Technetium pyrophosphate uptake in transthyretin cardiac amyloidosis: Associations with echocardiographic disease severity and outcomes.

BACKGROUND: Quantitative uptake of Technetium 99 m-pyrophosphate (TcPYP) is sensitive and specific for diagnosing transthyretin cardiac amyloidosis (ATTR). We sought to examine the association between TcPYP uptake intensity and echocardiographic measures of disease severity and clinical outcomes. METHODS AND RESULTS: A retrospective analysis was performed of 75 patients who underwent TcPYP scintigraphy. Planar images were evaluated semiquantitatively and using heart-to-contralateral lung (H/CL) ratio. The associations between H/CL ratio and echocardiographic parameters and outcomes were evaluated using linear regression and Cox models, respectively. There were 48 patients diagnosed with ATTR with mean H/CL ratio 1.58 ± 0.22 (vs 1.08 ± 0.09 if semiquantitative score = 0). The H/CL ratio was not associated with any measured echocardiographic parameter. Both semiquantitative uptake grade and H/CL ratio were associated with all-cause mortality (P = 0.009 and 0.007, respectively) and all-cause mortality or heart failure hospitalization (P = 0.001 and 0.020, respectively); however, neither were associated with outcomes when limited to patients with confirmed ATTR (P = 0.18 and 0.465, respectively). CONCLUSION: In patients with suspected ATTR, quantitative and semiquantitative uptake intensity of TcPYP is associated with all-cause mortality as well as all-cause mortality or heart failure hospitalization. However, in those with confirmed ATTR, there is no association with echocardiographic disease severity or outcomes.

Do myocardial PET-MR and PET-CT FDG images provide comparable information?

INTRODUCTION: Although positron emission tomography PET-MR imaging is emerging into clinical practice, many aspects of this imaging technique such as attenuation correction have yet to be validated for myocardial imaging. Thus, it is uncertain whether PET-MR FDG images provide clinical information which is comparable to PET-CT FDG images. The study goal was to systematically compare relative myocardial FDG concentrations obtained from cardiac PET-MR images to those derived from same day PET-CT images. METHODS: Myocardial FDG images of 27 patients undergoing PET-CT imaging, followed by PET-MR imaging 42 ± 13 minutes later as part of a prospective oncology study were analyzed. Mean segmental standardized uptake measurements (SUVmean) were obtained in each of the 17 standard myocardial segments and normalized to the brightest segment. RESULTS: Normalized segmental SUVmean values did not differ significantly between the PET-MR and PET-CT images (mean difference 0.002, P = .826). The specific segment was a marginally significant predictor of the differences (P = .057), with the largest difference in the anteroseptal basal segment. CONCLUSIONS: PET-MR, vis-à-vis PET-CT, does not significantly raise segmental uptake relative to the brightest segment, suggesting that PET-MR can be used similarly to PET-CT for applications where relative uptake is important.

Effect of stress testing on left ventricular mechanical synchrony by phase analysis of gated positron emission tomography in patients with normal myocardial perfusion.

PURPOSE: There are limited data on whether differences exist in left ventricular (LV) mechanical dyssynchrony indices derived from stress versus rest gated positron emission tomography (PET) in patients with normal myocardial perfusion imaging (MPI). METHODS: Stress/rest (82)Rb gated PET was performed in consecutive patients with normal MPI between 2006 and 2010. Patients were divided into two groups: group 1 [LV ejection fraction (EF) ≥ 55% and QRS < 120 ms] and group 2 (LVEF ≤35%). Images were acquired on a dedicated PET scanner prior to and on a hybrid PET/CT system after November 2008. LV dyssynchrony indices [phase standard deviation (SD)° and SD (ms)] were derived from stress and rest gated images. RESULTS: There were 91 patients in group 1 (age 61 ± 13, LVEF 66 ± 8%, normal QRS) and 126 in group 2 (age 66 ± 12, LVEF 25 ± 7%). The stress derived LVEF were significantly higher than rest for either group (p < 0.0001). Patients with cardiomyopathy had significantly higher dyssynchrony indices compared to those with normal LVEF (rest SD° 49.2 ± 21.5° vs 16.8 ± 7.8° and stress SD° 42.5 ± 19.4° vs 12.4 ± 3.7°, respectively, p < 0.0001 for both). The dyssynchrony indices derived from rest gated images were significantly higher than those derived from stress in both groups (p < 0.001 by unpaired and paired t test) and irrespective of the type of PET scanner utilized. Finally, 20/87 (23%) patients with normal LVEF and 27/66 (41%) of those with cardiomyopathy but without dyssynchrony based on stress indices were recategorized as having significant dyssynchrony given their resting indices. CONCLUSION: LV mechanical dyssynchrony indices by phase analysis are smaller when derived from peak stress versus rest gated PET imaging in patients with normal MPI, irrespective of the resting LVEF.

Predictors and incremental prognostic value of left ventricular mechanical dyssynchrony response during stress-gated positron emission tomography in patients with ischemic cardiomyopathy.

OBJECTIVES: The study sought to investigate whether there is stress-induced worsening of left ventricular mechanical dyssynchrony (LVMD) in patients with ischemic cardiomyopathy (ICM), determine the predictors of LVMD response (LVMDR) and its incremental prognostic value. BACKGROUND: The effect of stress physiology on LVMD in patients with ICM has not been adequately evaluated, and the prognostic value of abnormal LVMDR beyond traditional predictors of mortality remains uncertain. METHODS: 489 consecutive patients with ICM, LV ejection fraction (EF) <35% undergoing rest/stress Rb-82 gated PET were evaluated. LVMD was determined by phase analysis (SD) from gated rest and peak stress images; LVMDR was defined as stress SD - rest SD, and stratified by tertiles. All-cause mortality was the primary outcome. Linear regression was performed to determine the predictors of LVMDR, and Cox proportional hazard modeling to assess its independent prognostic value. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were performed to determine incremental value of abnormal LVMDR. RESULTS: Independent predictors of worse LVMD at peak stress were perfusion defect size (PDS) and resting heart rate; while higher resting LVEF, LVEF reserve and rest phase SD were associated with lower LVMDR. Over a mean follow-up of 2.0 ± 1.4 years, 123 patients (25%) died. After multivariate analysis, LVMDR was an independent predictor of all-cause mortality (HR 1.19[1.01;1.38], per 10° increase, P = .04) and reclassified 18% of patients with IDI 1.4% (P = .02) and NRI 9% (P = .057). CONCLUSION: In patients with ICM, an increase of LVMD during peak gating stress as compared to rest was an independent predictor of all-cause mortality, and had a modest incremental prognostic value. Future studies are needed to validate our findings.

Lessons from regadenoson and low-level treadmill/regadenoson myocardial perfusion imaging: initial clinical experience in 1263 patients.

BACKGROUND: Regadenoson is a pharmacologic stress agent, which was recently approved for stress myocardial perfusion imaging (MPI). Aside from the initial protocol-driven studies, clinical experience with this stress agent is limited. Furthermore, low-level treadmill testing in a large population with regadenoson has not previously been evaluated. We describe our experience in the first 6 months of routine inpatient and outpatient clinical use. METHODS: Between 7/1/08 and 12/04/08, 1263 patients underwent regadenoson stress testing (596 with low-level treadmill, 667 supine). Past medical history, clinical symptoms during stress, and changes in systolic blood pressure were prospectively recorded. RESULTS: Low-level treadmill testing was well tolerated in our patient population. Shortness of breath, dizziness, palpitations, transient heart block, and nausea were less frequent when patients were able to exercise. In our population, 51% experienced a drop in systolic blood pressure greater than 10 mmHg, with 9% experiencing a decrease in more than 30 mmHg. This decrease in blood pressure was more common in patients who underwent low-level treadmill testing vs those that were supine (56% vs 47%, P-value < 0.001). The frequency of symptoms in our entire population was as follows: chest pain 35%, dizziness/lightheadedness 16%, shortness of breath 27%, headache 1.4%, nausea 2.3%, and palpitations 5%. There were no major hemodynamic or conduction abnormalities. In the 16% of patients, a history of COPD/Asthma Regadenoson MPI was well tolerated. There were no procedural deaths. CONCLUSION: Regadenoson and Regadenoson combined with low level exercise MPI appear to be safe and well tolerated. An asymptomatic fall in systolic blood pressure seems to be more common in patients who undergo low-level treadmill testing.

SPECT/CT imaging: clinical utility of an emerging technology.

Single-photon emission computed tomography (SPECT) has been a mainstay of nuclear medicine practice for several decades. More recently, combining the functional imaging available with SPECT and the anatomic imaging of computed tomography (CT) has gained more acceptance and proved useful in many clinical situations. Most vendors now offer integrated SPECT/CT systems that can perform both functions on one gantry and provide fused functional and anatomic data in a single imaging session. In addition to allowing anatomic localization of nuclear imaging findings, SPECT/CT also enables accurate and rapid attenuation correction of SPECT studies. These attributes have proved useful in many cardiac, general nuclear medicine, oncologic, and neurologic applications in which the SPECT results alone were inconclusive. Optimal clinical use of this rapidly emerging imaging modality requires an understanding of the fundamental principles of SPECT/CT, including quality control issues as well as potential pitfalls and limitations. The long-term clinical and economic effects of this technology have yet to be established.

Impact of Time-of-Flight Reconstruction on Cardiac PET Images of Obese Patients.

PURPOSE: The benefit of time-of-flight (TOF) information in PET oncology studies is well established, demonstrating improved signal-to-noise ratio and enhanced lesion detection. In cardiac PET studies, tracer distribution and study interpretation differ substantially from oncology PET, and the benefit of TOF is less established. We investigate the impact of TOF on reconstructed myocardial distribution in Rb PET perfusion studies of obese patients, for whom TOF would have most significant impact. METHODS: Cardiac Rb PET data of 13 obese patients (8 male, 5 female patients; weight, mean, 139 kg [range, 109-191 kg]; body mass index, mean, 49 kg/m [range, 36-76 kg/m]) were analyzed retrospectively. Images were reconstructed with and without TOF and with varying number of iterative updates (2-12 iterations). Convergence and clinical relevance of differences were assessed both visually and quantitatively (automated 17-segment scoring). An anthropomorphic torso phantom also was scanned in order to study how TOF affects reconstruction of a myocardial distribution. RESULTS: Time-of-flight imaging provided significant improvement in image quality and convergence rate compared with non-TOF imaging. Time-of-flight reconstruction typically required 2 to 4 iterations to converge versus 8 to 12 iterations for non-TOF reconstruction. Even at 12 iterations, non-TOF images occasionally had apparent differences in relative perfusion compared with TOF images that exceeded 10% and were considered likely to affect clinical interpretation. CONCLUSIONS: Time-of-flight reconstruction has a significant clinical impact on cardiac PET in obese patients. When interpreting cardiac studies from non-TOF-capable PET scanners, one must ensure to reconstruct images with sufficient iterations and to be aware of potential artifacts.

A knowledge-based method for reducing attenuation artefacts caused by cardiac appliances in myocardial PET/CT.

Attenuation artefacts due to implanted cardiac defibrillator leads have previously been shown to adversely impact cardiac PET/CT imaging. In this study, the severity of the problem is characterized, and an image-based method is described which reduces the resulting artefact in PET. Automatic implantable cardioverter defibrillator (AICD) leads cause a moving-metal artefact in the CT sections from which the PET attenuation correction factors (ACFs) are derived. Fluoroscopic cine images were measured to demonstrate that the defibrillator's highly attenuating distal shocking coil moves rhythmically across distances on the order of 1 cm. Rhythmic motion of this magnitude was created in a phantom with a moving defibrillator lead. A CT study of the phantom showed that the artefact contained regions of incorrect, very high CT values and adjacent regions of incorrect, very low CT values. The study also showed that motion made the artefact more severe. A knowledge-based metal artefact reduction method (MAR) is described that reduces the magnitude of the error in the CT images, without use of the corrupted sinograms. The method modifies the corrupted image through a sequence of artefact detection procedures, morphological operations, adjustments of CT values and three-dimensional filtering. The method treats bone the same as metal. The artefact reduction method is shown to run in a few seconds, and is validated by applying it to a series of phantom studies in which reconstructed PET tracer distribution values are wrong by as much as 60% in regions near the CT artefact when MAR is not applied, but the errors are reduced to about 10% of expected values when MAR is applied. MAR changes PET image values by a few per cent in regions not close to the artefact. The changes can be larger in the vicinity of bone. In patient studies, the PET reconstruction without MAR sometimes results in anomalously high values in the infero-septal wall. Clinical performance of MAR is assessed by two physicians' inspection of images generated in 30 patients with and without MAR. Noticeable image differences are judged in 14 of 28 (50%) observations with AICD leads, and significant clinical impact is judged in 2 of 28 (7%) of those observations. A polar map analysis shows significant differences in 10 of 14 (71%) studies with AICD leads, and 0 of 16 (0%) studies without AICD leads. These results show that the MAR method is successful in reducing the magnitude of the metal artefact without incorrectly altering cases without metal artefact. In spite of profound changes to the CT image from the moving metal, the PET ACF in that study was changed by no more than 20%.

PET and PET/CT imaging: what clinicians need to know.

Positron emission tomography (PET), once the sole province of academic medical centers, is rapidly being adopted in daily clinical practice in community hospitals and outpatient centers. It can be especially useful in oncology, cardiology, and neurology. We provide an overview of the fundamentals of PET and PET with computed tomography (PET/CT) and discuss their current clinical utility.

Ischemic and viable myocardium in patients with non-Q-wave or Q-wave myocardial infarction and left ventricular dysfunction: a clinical study using positron emission tomography, echocardiography, and electrocardiography.

OBJECTIVES: We investigated whether patients with non-Q-wave myocardial infarction (NQMI) have more ischemic viable myocardium (IVM) than patients with Q-wave myocardial infarction (QMI). BACKGROUND: Non-Q-wave myocardial infarction is associated with higher incidences of cardiac events than QMI, suggesting more myocardium at risk in NQMI. METHODS: To identify myocardial ischemia, hibernation, and scar, the resting and stress (82)rubidium perfusion and F-18 fluorodeoxyglucose metabolic positron emission tomographic imaging (PET) was performed in 64 consecutive patients with NQMI (n = 21) or QMI (n = 43). Echocardiography was performed for assessment of left ventricular function and wall motion index (WMI). The relationships between PET, echocardiographic, and electrocardiographic findings were analyzed. RESULTS: There were no significant differences in left ventricular ejection fraction (LVEF) between NQMI and QMI groups (28 +/- 10% vs. 25 +/- 11%, p > 0.05). Ischemic and viable myocardium was more common in NQMI than in QMI (91% vs. 61%, p < 0.05). The total amount of IVM was significantly higher in NQMI than in QMI (6.5 +/- 5.2 vs. 2.9 +/- 2.8 segments, p < 0.001). Neither the number of Q waves, residual ST-segment depression of >or=0.5 mm or elevation of >or=1 mm, nor LVEF and WMI were significant predictors for IVM. Wall motion index correlated with scar segments (r = 0.54, p < 0.001) and LVEF (r = -0.67, p < 0.001). CONCLUSIONS: Ischemic and viable myocardium is common in patients with NQMI and left ventricular dysfunction, suggesting that aggressive approaches should be taken to salvage the myocardium at risk in such patients.

Prediction of death or myocardial infarction by exercise single photon emission computed tomography perfusion scintigraphy in patients who have had recent coronary artery stenting.

BACKGROUND: Although practice guidelines do not recommend routine exercise testing of patients after coronary stenting, several small studies have suggested that stress myocardial perfusion imaging can provide prognostic information about future adverse cardiac events. We sought to determine if exercise nuclear testing provides independent prognostic information in patients after coronary stenting. METHODS: We analyzed the outcomes of 370 patients who underwent dual isotope exercise nuclear scintigraphy at least 1 month after coronary stenting and had testing between April 1996 and May 2002. Patients were classified according to presence or absence of any ischemia. The primary endpoint was all-cause mortality or myocardial infarction (MI) during a median of 30 months (range 6-59) of follow-up. RESULTS: There were 86 patients (23%) who had ischemia. Major events--death or MI--occurred in 62 patients including 22 deaths. Among patients with no ischemia, the 30-month event rate was 9.1%, whereas among patients with ischemia, the event rate was 17.0% (P = .001). After adjusting for age, sex, standard cardiac risk factors, cardiac history, left ventricular ejection fraction, angiographic findings, procedural variables, exercise capacity, and heart-rate dynamics, the presence of scintigraphic evidence of ischemia predicted death or MI (adjusted hazard ratio 2.08, 95% CI 1.21-3.56, P = .008). The presence of ischemia similarly predicted events in asymptomatic patients (adjusted hazard ratio 2.19, 95% CI 1.17-4.11, P = .015). CONCLUSIONS: In patients with recent coronary stent placement, reversible nuclear perfusion defects independently predicted risk of death or MI.

Do implanted pacemaker leads and ICD leads cause metal-related artifact in cardiac PET/CT?

UNLABELLED: Artifacts related to metallic implants are an established limitation of CT-based attenuation correction (CT-AC) in PET/CT. However, the impact of metallic components of pacemaker leads and implantable cardioverter defibrillator (ICD) leads on the accuracy of cardiac PET has not been evaluated. The goal of this study was to investigate the magnitude of artifacts related to pacing and defibrillation leads in both phantom and patient studies. METHODS: Images were acquired on a PET/CT scanner using CT-AC and were compared with those obtained on a dedicated PET scanner using transmission source-based attenuation correction. Phantoms consisting of pacemaker leads and ICD leads submerged in uniform background activity solution were imaged, and regions were analyzed to measure radionuclide concentrations at known lead locations relative to background. In addition, 15 cardiac 18F-FDG patients (having either pacing leads, defibrillation leads, or both) were imaged on both PET/CT and PET scanners. Images were visually and quantitatively assessed to determine whether artifact related to the implanted leads was present and, if so, its severity relative to surrounding myocardium. RESULTS: In phantom studies, artifacts caused by pacing lead electrodes were barely noticeable, but artifacts arising from highly radioopaque ICD shock coil electrodes were clearly apparent. In the patient studies, no artifacts from pacing leads were identified. However, significant artifact was observed in 50% of the patient studies with ICD leads. In the affected areas, local myocardial uptake in PET/CT images using CT-AC was, on average, 30% higher than that in the corresponding PET images. CONCLUSION: Although pacemaker leads do not appear to cause artifact in cardiac PET/CT images, ICD leads frequently do result in artifacts of sufficient magnitude to impact clinical image interpretation. Accordingly, software-based corrections in CT-AC algorithms appear necessary for accurate cardiac imaging with PET/CT.

Transmission Imaging in Lymphoscintigraphy with a 153Gd Flood Source.

UNLABELLED: Lymphoscintigraphy uses intradermal or interstitial injections of (99m)Tc-labeled tracers to produce images of focal lymph nodes. Because there is little or no anatomic information in the (99m)Tc images, a (57)Co flood source is sometimes used to provide transmission data along with the emission data. The anatomic shadow from the transmission scan generally improves interpretation and surgical planning. However, the (57)Co transmission photons contribute to background on the (99m)Tc images, reducing contrast and signal-to-noise ratio (SNR). SNR is related to lesion detection, and some lymph nodes that would be detected in an emission-only scan might not be detected if acquired with a (57)Co flood source. An alternative to a (57)Co flood source is a (153)Gd flood source, which has primary photon emissions well below the (99m)Tc emission window, allowing the shadow to be acquired in a separate transmission window. Significantly smaller crosstalk from (153)Gd should improve SNR and therefore would be expected to improve lymph node detection. We hypothesized that the use of a (153)Gd flood source would reduce background and improve SNR for these studies. METHODS: Phantom studies simulating lymphoscintigraphy were performed to compare performance with a (153)Gd flood source, a (57)Co flood source, and no flood source. SNR in the (99m)Tc emission images was measured using a water phantom to simulate patient body and point sources of various activities to simulate nodes and injection site. The encouraging phantom studies prompted use of the (153)Gd flood source in routine clinical breast lymphoscintigraphy, melanoma lymphoscintigraphy, and lymphedema studies. Because emission and transmission data were acquired in separate energy windows, fused planar images of emission and transmission data were available to the physician. RESULTS: SNR was highest with no flood source and was lowest with the (57)Co flood source by a significant margin. SNR with the (153)Gd flood source was similar to that with no flood source on the anterior (transmission) view. SNR was reduced somewhat in the posterior (nontransmission) view because of attenuation of signal by the flood source itself. Minor crosstalk in the (99m)Tc window was observed with the (153)Gd flood source, attributed to simultaneous detection of x-ray photons and gamma-photons. This crosstalk was reduced by introducing thin metal filters to absorb most x-ray photons, at the expense of more attenuation in the posterior view. Unlike with the (57)Co flood source, a usable posterior view (with anatomic shadow derived from the anterior view) was generated with the (153)Gd flood source. Clinical lymphoscintigraphy images with the (153)Gd flood source were of high quality. Interpretation was aided by the ability to control image mixing and brightness and contrast of separate color scales. CONCLUSION: By producing fused images with reduced crosstalk and improved image quality, a (153)Gd flood source offers advantages over a conventional (57)Co flood source for anatomic shadowing in lymphoscintigraphy. Lymph nodes in emission images have higher SNR, indicating a likely improvement in clinical lesion detection. Separate emission and transmission images provide additional flexibility in image display during interpretation.

Outcome of cardiac sarcoidosis after radiofrequency ablation and placement of AICD- A propensity matched analysis.

BACKGROUND: Cardiac Sarcoidosis (CS) can lead to life-threatening ventricular dysrhythmias and sudden death. Immunosuppressive medications, radiofrequency ablation (RFA), and implantable cardioverter defibrillators (ICD) have been utilized to manage ventricular dysrhythmias but their benefits remain poorly defined. OBJECTIVE: The aim of this study is to assess the durability of RFA in CS population and to determine outcome predictors after RFA. METHODS: We compared the CS patients who had RFA±ICD against those with only ICD placement and contemporaneous patients with arrhythmogenic right ventricular dysplasia (ARVD) who had RFA. We analyzed time to a composite first event of appropriate ICD therapy, subsequent RFA, cardiac transplantation or death. We also evaluated variables predicting recurrence of ventricular dysrhythmias, including LVEF, cardiac involvement on PET scan, percent of ventricular ectopic beats, number of inducible VT foci and success of the RFA procedure. We used propensity matching and multivariable regression to adjust for baseline differences between the groups to identify outcome predictors. RESULTS: Thirty ablations for VT were performed in 20 CS patients (13 had concomitant ICD placement); 12 ablations were done in eight ARVD patients and 33 CS patients with only ICD placements were included in this cohort. The median follow-up period was 48 (9-173) months. Fourteen (70%) patients reached composite end points after RFA compared to 13 (63%) following ICD placement and five (87%) in the ARVD cohort. There was a significant time difference to reach composite end points (p=0.02) in favor of ICD only cohort. The median number of ICD therapies were higher in the CS-RFA group (p=0.01). The requirement for ICD therapy increased over time following RFA, especially after 12 months. Variables predicting earlier time-to-event were EF <40% (OR=13.2) and unsuccessful RFA procedure (OR=7.9). The presence of more than one inducible VT morphology was associated with higher likelihood of unsuccessful RFA (p=0.03). CONCLUSION: RFA can be an effective modality for the short-term treatment of ventricular dysrhythmias in cardiac sarcoidosis; however, after more than 12 months, the number of appropriate therapies escalates. Accordingly, ICD placement is recommended for all patients who undergo RFA for VT associated with CS, whether it is successful or not. Low LVEF and unsuccessful ablation were strong predictors of future events.

Importance of ischemic and viable myocardium for patients with chronic ischemic mitral regurgitation and left ventricular dysfunction.

The objective of this investigation is to determine the importance of ischemic viable myocardium for clinical outcomes in patients with severe chronic ischemic mitral regurgitation and severe left ventricular dysfunction undergoing surgical correction of mitral regurgitation. The study included 54 patients with left ventricular ejection fraction of 27 +/- 9%. Positron emission tomography was performed preoperatively for the identification of ischemic viable myocardium. The patients with a large amount of ischemic viable myocardium (> or =5 segments) had significantly lower 6-month mortality rates than those with less viable myocardium (0 to 4 segments) after the surgery.