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.

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.

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.

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.

Predictive value of exercise myocardial perfusion imaging in the Medicare population: the impact of the ability to exercise.

BACKGROUND: Although the prognostic value of quantitative single photon emission computed tomography myocardial perfusion imaging (MPI) with exercise and pharmacologic stress is well established, the prognostic and management value in the Medicare age population is less clear. METHODS: The prospectively populated Cleveland Clinic nuclear cardiology database was used to identify 5,994 consecutive pateints, age >65 years [1,664 (28%) exercise MPI, mean age 72.4±5.1, 74% male], who underwent MPI between January 2004 and January 2008. Clinical baseline variables, post test 90 days revascularization and MPI variables were analyzed. Overall and stratified nonparametric survival estimates were obtained by Kaplan-Meier method. Median follow-up time was 2.4 years. Parametric hazard modeling with bootstrap bagging methods was used to determine prognostic variables predicting mortality. RESULTS: There was no difference in mortality in patients with an abnormal MPI vs. those with normal MPI. Amongst the patients who underwent exercise MPI, there were 103 (6%) deaths and 121 (8.2%) revascularizations. Only lower exercise capacity (<7 METs) and higher end systolic volume (ESV) predicted mortality. Although a larger amount of ischemia influenced down stream revascularization ischemia, revascularization of patients with an abnormal exercise MPI did not offer a survival benefit (log rank P value=0.01). CONCLUSIONS: In the a Medicare age population, exercise MPI perfusion variables influenced rates of revascularization but failed to provide incremental significant risk-stratification beyond exercise capacity. Maximum METs achieved appears to be a better predictor of survival.

Identification of therapeutic benefit from revascularization in patients with left ventricular systolic dysfunction: inducible ischemia versus hibernating myocardium.

BACKGROUND: Although the recent surgical treatment of ischemic heart failure substudy reported that revascularization of viable myocardium did not improve survival, these results were limited by the viability imaging technique used and the lack of inducible ischemia information. We examined the relative impact of stress-rest rubidium-82/F-18 fluorodeoxyglucose positron emission tomography identified ischemia, scar, and hibernating myocardium on the survival benefit associated with revascularization in patients with systolic dysfunction. METHODS AND RESULTS: The extent of perfusion defects and metabolism-perfusion mismatch was measured with an automated quantitative method in 648 consecutive patients (age, 65±12 years; 23% women; mean left ventricular ejection fraction, 31±12%) undergoing positron emission tomography. Follow-up time began at 92 days (to avoid waiting-time bias); deaths before 92 days were excluded from the analysis. During a mean follow-up of 2.8±1.2 years, 165 deaths (27.5%) occurred. Cox proportional hazards modeling was used to adjust for potential confounders, including a propensity score to adjust for nonrandomized treatment allocation. Early revascularization was performed within 92 days of positron emission tomography in 199 patients (33%). Hibernating myocardium, ischemic myocardium, and scarred myocardium were associated with all-cause death (P=0.0015, 0.0038, and 0.0010, respectively). An interaction between treatment and hibernating myocardium was present such that early revascularization in the setting of significant hibernating myocardium was associated with improved survival compared with medical therapy, especially when the extent of viability exceeded 10% of the myocardium. CONCLUSIONS: Among patients with ischemic cardiomyopathy, hibernating, but not ischemic, myocardium identifies which patients may accrue a survival benefit with revascularization versus medical therapy.

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.

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.

Ischemic changes on rubidium-82 positron emission tomography imaging are associated with left ventricular functional and volumetric change independent of metabolic properties and echocardiographic functional variables in ischemic cardiomyopathy.

Positron emission tomography (PET) imaging allows identification of stress-induced ischemia and myocardial viability in patients with ischemic cardiomyopathy. We assessed the left ventricular (LV) functional response to vasodilator stress in patients with advanced ischemic cardiomyopathy undergoing pharmacologic stress (PET) perfusion and metabolic imaging. Additionally, we aimed to determine if mitral regurgitation (MR), right ventricular (RV) dysfunction and diastolic function influenced the observed LV responses to pharmacologic stress. In 161 patients (81% men; 65 ± 13 years), PET and echocardiography were performed within a week for noninvasive evaluation of myocardial ischemia and viability (scored using 17-segment model), as well as ventricular and valvular function. Patients were stratified based on ischemic defects in any segments versus hibernation/scar defects only. The LV volumes, EF by gating and transient ischemic dilatation (TID) index were generated automatically. Wall thickening (WT) scores were determined visually. The subgroup with reversible/ischemic segments on PET imaging (N = 55) exhibited greater end-systolic (ESV) and end-diastolic volume (EDV) enlargement during stress (13 ± 22 and 16 ± 43 ml increase respectively, vs. 0 ± 18 ml [P < 0.0001] and 2 ± 24 ml [P = 0.01]), a decrease in LVEF during stress (mean -3% vs. +2%), and greater TID indices (mean 1.13 ± 0.18 vs. 1.02 ± 0.12) compared to hibernation/scar only (N = 92). In addition, mean WT scores during stress declined significantly only in the ischemic subgroup (P < 0.0001 for regional LAD, non-LAD and global wall thickening scores). The prevalence and the severity of MR and RV dysfunction did not differ between groups. By univariate analysis, global and LAD territory segmental ischemia, global sum stress score (SSS), TID index, resting EF, ESV enlargement during stress, as well as global WT changes correlated with post-stress LVEF decline. Multivariate predictors included SSS, resting LVEF, and ESV change. Ischemic changes on vasodilator PET imaging are associated with global LV functional decline and volumetric dilatation, presumably due to stunning effect. Severity of RV dysfunction and MR had limited impact on the above changes.

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.

Preliminary data on the diagnostic accuracy of rubidium-82 cardiac PET perfusion imaging for the evaluation of ischemia in a pediatric population.

Evaluation of myocardial perfusion is sometimes necessary in children with congenital heart disease or acquired coronary artery abnormalities. Limited information is available regarding the clinical utility of myocardial perfusion imaging in children. PET imaging with rubidium-82 may provide a convenient clinical means of assessing regional circulatory compromise in pediatric patients with small hearts, due to its improved spatial resolution. Clinically indicated cardiac PET studies obtained in 22 pediatric patients were reviewed by two blinded observers and assigned myocardial perfusion scores using a standard 17-segment model. PET results were correlated with coronary angiography, available in 15 cases, to determine the accuracy of PET scanning for evaluating compromise of the myocardial circulation. Reversible defects consistent with myocardial ischemia were present in 6 of 15 (40%) PET cases. The sensitivity and specificity of cardiac PET for the detection of significant coronary artery disease were 100% and 82%, respectively. The positive predictive value of cardiac PET was 67%, while the negative predictive value was 100%. Cardiac PET imaging with rubidium-82 appears promising for the noninvasive assessment of myocardial perfusion in the pediatric population. The findings from this small series suggest that prospective study in a larger patient cohort merits consideration.