Non-cardiac uptake of technetium-99m pyrophosphate in transthyretin cardiac amyloidosis.

BACKGROUND: Technetium-based bone scintigraphy is rapidly becoming the most common non-invasive imaging tool in the diagnosis of Transthyretin cardiac amyloidosis (ATTR). Skeletal muscle uptake has been described with technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (TcDPD), and may account for masking of bony uptake. We sought to investigate skeletal muscle uptake of technetium-99m-pyrophosphate (TcPYP) in patients with ATTR. METHODS AND RESULTS: This was a retrospective analysis of 57 patients diagnosed with ATTR who underwent TcPYP scintigraphy. Cardiac uptake was assessed on whole-body planar imaging using a semiquantitative scale (grades 0 to 3) and on single-photon emission computed tomography (SPECT) with CT attenuation correction using total myocardial counts per voxel after a 3-hour incubation. Skeletal muscle (psoas and biceps), vertebral body, LV myocardium, and blood pool mean counts were calculated. In the cohort (age 78 ± 9 years, 77% male, and 30% hereditary ATTR), there was no visualized tracer uptake in skeletal muscle or soft tissue on qualitative SPECT assessment. Total and blood pool-corrected uptake in the muscle groups were significantly less than myocardium and bone (P < 0.001). Blood pool-corrected muscle uptake was not associated with semiquantitative grade 3 vs 2 uptake (psoas P = 0.66, biceps P = 0.13) or presence of hereditary ATTR (psoas P = 0.43, biceps P = 0.69). As bony uptake decreased, there was no corresponding increase in skeletal muscle uptake. CONCLUSIONS: In patients with ATTR cardiac amyloidosis, skeletal muscle uptake of TcPYP is minimal when assessed by qualitative and quantitative metrics, and is not significantly different in patients with grade 2 vs 3 semiquantitative uptake. The properties of this tracer may be different than TcDPD with respect to non-cardiac uptake.

Correction to: Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC.

The above position statement originally published containing errors in the author metadata; specifically, the Expert Content Reviewers-Andrew Einstein, Raymond Russell and James R. Corbett-were tagged as full authors of the paper. The article metadata has now been corrected to remove Drs. Einstein, Russell and Corbett from the author line, and the PubMed record has been updated accordingly.

Status of cardiovascular PET radiation exposure and strategies for reduction: An Information Statement from the Cardiovascular PET Task Force.

Cardiovascular positron emission tomography (PET) imaging provides high-quality visual and quantitative myocardial perfusion and function images. In addition, cardiovascular PET can assess myocardial viability, myocardial inflammatory disorders such as cardiac sarcoid, and infections of implanted devices including pacemakers, ventricular assist devices, and prosthetic heart valves. As with all nuclear cardiology procedures, the benefits need to be considered in relation to the risks of exposure to radiation. When performed properly, these assessments can be obtained while simultaneously minimizing radiation exposure. The purpose of this information statement is to present current concepts to minimize patient and staff radiation exposure while ensuring high image quality.

Approaches to enhancing radiation safety in cardiovascular imaging: a scientific statement from the American Heart Association.

Education, justification, and optimization are the cornerstones to enhancing the radiation safety of medical imaging. Education regarding the benefits and risks of imaging and the principles of radiation safety is required for all clinicians in order for them to be able to use imaging optimally. Empowering patients with knowledge of the benefits and risks of imaging will facilitate their meaningful participation in decisions related to their health care, which is necessary to achieve patient-centered care. Limiting the use of imaging to appropriate clinical indications can ensure that the benefits of imaging outweigh any potential risks. Finally, the continually expanding repertoire of techniques that allow high-quality imaging with lower radiation exposure should be used when available to achieve safer imaging. The implementation of these strategies in practice is necessary to achieve high-quality, patient-centered imaging and will require a shared effort and investment by all stakeholders, including physicians, patients, national scientific and educational organizations, politicians, and industry.

Regadenoson provides perfusion results comparable to adenosine in heterogeneous patient populations: a quantitative analysis from the ADVANCE MPI trials.

BACKGROUND: Total and reversible left ventricular (LV) perfusion defect size (PDS) predict patient outcome. Limited data exist as to whether regadenoson induces similar perfusion abnormalities as observed with adenosine. We sought to determine whether regadenoson induces a similar LV PDS as seen with adenosine across varying patient populations. METHODS AND RESULTS: ADVANCE MPI were prospective, double-blind randomized trials comparing regadenoson to standard adenosine myocardial perfusion tomography (SPECT). Following an initial adenosine SPECT, patients were randomized to either regadenoson (N = 1284) or a second adenosine study (N = 660). SPECT quantification was performed blinded to randomization and image sequence. Propensity analysis was used to define comparability of regadenoson and adenosine perfusion results. Baseline clinical and SPECT results were similar in the two randomized groups. There was a close correlation between adenosine and regadenoson-induced total (r (2) = 0.98, P < .001) and reversible (r (2) = 0.92, P < .001) PDS. Serial differences in total (0.00 ± 3.51 vs -0.11 ± 3.46, P = .51) and reversible (0.15 ± 3.79 vs 0.07 ± 3.33, P = .65) PDS were also comparable in patients randomized to regadenoson vs adenosine, respectively, and irrespective of age, gender, diabetic status, body mass index, or prior cardiovascular history. By propensity analysis, regadenoson-induced total PDS was significantly larger than observed with adenosine. CONCLUSION: This is the first study to show that regadenoson induces similar, if not larger, perfusion defects than those observed with adenosine across different patient populations and demonstrates the value of quantitative analysis for defining serial changes in SPECT perfusion results. Regadenoson should provide comparable diagnostic and prognostic SPECT information to that obtained with adenosine.

Prognostic value of left ventricular mechanical dyssynchrony by phase analysis in patients with non-ischemic cardiomyopathy with ejection fraction 35-50% and QRS < 150 ms.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) by phase analysis of gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful tool for predicting response to cardiac resynchronization therapy and has prognostic value. While most of the studies were done on patients with ischemic cardiomyopathy or those with LV ejection fraction (EF) < 35%, there are little data on the prognostic value of LVMD in patients with non-ischemic cardiomyopathy (NICM), particularly those with mildly decreased systolic function and narrow or intermediate QRS duration. METHODS AND RESULTS: From the stress SPECT-MPI database at Cleveland Clinic, we identified 324 consecutive patients (mean age 62 ± 13 years, 62% male, 36% diabetics) with NICM, LVEF 35-50% (median [Q1,Q3] 45 [41,49]), and QRS < 150 ms (13% with QRS 120-149 ms). LVMD was determined from gated stress images and expressed as phase standard deviation (SD) and histogram BW (% R-R cycle). For easier graphical illustration, patients were divided into tertiles of LVMD. All-cause death was the primary endpoint and determined using the Social Security Death Index. Cox proportional hazard model was performed to determine the independent predictive value of LVMD, and next Cox models for incremental value. After a mean follow-up time of 1,689 days, 86 (26.5%) of patients died. These patients were older, had more diabetes, more use of diuretics, with wider QRS duration, and with a trend for higher phase SD and BW. After adjusting for age, hypertension, diabetes, aspirin, beta-blockers, diuretics, QRS, and EF, phase SD was an independent predictor of all-cause mortality with hazard ratio [95% CI] 1.97 [1.06,3.66] for the highest tertile, and added incremental prognostic value (P = .025). Similar findings were obtained using histogram BW. CONCLUSION: In patients with NICM, EF 35-50%, and QRS < 150 ms, increased LVMD on peak stress SPECT was an independent predictor of all-cause mortality. The utility and applicability of such findings in clinical practice need further evaluation in larger and prospective studies.

Stress positron emission tomography is safe and can guide coronary revascularization in high-risk patients being considered for transcatheter aortic valve replacement.

BACKGROUND: The safety and accuracy of regadenoson stress positron emission tomography (PET) in patients with significant aortic stenosis (AS) is unknown. In patients undergoing surgical aortic valve replacement, coronary artery bypass grafting for coronary artery disease is standard, but the appropriate revascularization strategy in patients undergoing TAVR is uncertain. Stress PET may identify patients that benefit from revascularization. METHODS: Fifty consecutive patients who were referred for consideration of TAVR and underwent a stress PET study were retrospectively identified. We assessed major adverse cardiac events and significant decreases in systolic blood pressure. The percentage of jeopardized myocardium was determined by combining ischemic and hibernating myocardium. RESULTS: Our patients were high risk with a mean Society of Thoracic Surgeons mortality score of 11.4% and had severe AS with a moderately reduced left ventricular ejection fraction (EF) (mean aortic valve area of 0.78 ± 0.25 cm(2) and mean EF of 39 ± 16%). There were no major adverse events during testing. Transient hypotension occurred in 16% of the patients. Revascularization was performed in 44% of patients, and 91% of these patients had revascularization to territories jeopardized on PET. These patients had substantial jeopardized myocardium (median 19%), and only 3 patients underwent revascularization despite less than 10% jeopardized myocardium. CONCLUSIONS: Stress cardiac PET with regadenoson can be performed safely in patients with severe AS. Results of the PET study can accurately direct subsequent revascularization.

Role of imaging in the diagnosis and management of patients with cardiac amyloidosis: state of the art review and focus on emerging nuclear techniques.

Amyloidosis is an infiltrative disease characterized by deposition of amyloid fibrils within the extracellular tissue of one or multiple organs. Involvement of the heart, cardiac amyloidosis, is recognized as a common cause of restrictive cardiomyopathy and heart failure. The two major types of cardiac amyloidosis are cardiac amyloid light-chain (AL) and transthyretin-related cardiac amyloidosis (ATTR, mutant and wild types) (Nat Rev Cardiol 2010;7:398-408). While early recognition of cardiac amyloidosis is of major clinical importance, so is the ability to differentiate between subtypes. Indeed, both prognosis and therapeutic options vary drastically depending on the subtype. While endomyocardial biopsy with immunostaining is considered the gold standard, advances in imaging provide an attractive non-invasive alternative. Currently, electrocardiography, echocardiography, and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy. Yet, none of these modalities can effectively differentiate the cardiac amyloid subtypes. Recent data with (99m)Tc-phosphate derivatives, previously used as bone seeking radioactive tracers, have shown promising results; these radiotracers selectively bind ATTR, but not AL subtype, and can differentiate subtypes with high diagnostic accuracy. This review will initially present the non-radionuclide imaging techniques and then focus on the radionuclide imaging techniques, particularly (99m)Tc-DPD and (99m)Tc-PYP, mechanism of action, performance and interpretation of the study, diagnostic accuracy, prognostic value, future clinical perspective, and outlook.

ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

The American College of Cardiology Foundation along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical presentations for stable ischemic heart disease (SIHD) to consider use of stress testing and anatomic diagnostic procedures. This document reflects an updating of the prior Appropriate Use Criteria (AUC) published for radionuclide imaging (RNI), stress echocardiography (Echo), calcium scoring, coronary computed tomography angiography (CCTA), stress cardiac magnetic resonance (CMR), and invasive coronary angiography for SIHD. This is in keeping with the commitment to revise and refine the AUC on a frequent basis. A major innovation in this document is the rating of tests side by side for the same indication. The side-by-side rating removes any concerns about differences in indication or interpretation stemming from prior use of separate documents for each test. However, the ratings were explicitly not competitive rankings due to the limited availability of comparative evidence, patient variability, and range of capabilities available in any given local setting. The indications for this review are limited to the detection and risk assessment of SIHD and were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Eighty clinical scenarios were developed by a writing committee and scored by a separate rating panel on a scale of 1-9, to designate Appropriate, May Be Appropriate, or Rarely Appropriate use following a modified Delphi process following the recently updated AUC development methodology. The use of some modalities of testing in the initial evaluation of patients with symptoms representing ischemic equivalents, newly diagnosed heart failure, arrhythmias, and syncope was generally found to be Appropriate or May Be Appropriate, except in cases where low pre-test probability or low risk limited the benefit of most testing except exercise electrocardiogram (ECG). Testing for the evaluation of new or worsening symptoms following a prior test or procedure was found to be Appropriate. In addition, testing was found to be Appropriate or May Be Appropriate for patients within 90 days of an abnormal or uncertain prior result. Pre-operative testing was rated Appropriate or May Be Appropriate only for patients who had poor functional capacity and were undergoing vascular or intermediate risk surgery with 1 or more clinical risk factors or an organ transplant. The exercise ECG was suggested as an Appropriate test for cardiac rehabilitation clearance or for exercise prescription purposes. Testing in asymptomatic patients was generally found to be Rarely Appropriate, except for calcium scoring and exercise testing in intermediate and high-risk individuals and either stress or anatomic imaging in higher-risk individuals, which were all rated as May Be Appropriate. All modalities of follow-up testing after a prior test or percutaneous coronary intervention (PCI) within 2 years and within 5 years after coronary artery bypass graft (CABG) in the absence of new symptoms were rated Rarely Appropriate. Pre-operative testing for patients with good functional capacity, prior normal testing within 1 year, or prior to low-risk surgery also were found to be Rarely Appropriate. Imaging for an exercise prescription or prior to the initiation of cardiac rehabilitation was Rarely Appropriate except for cardiac rehabilitation clearance for heart failure patients.

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.

Association of left ventricular mechanical dyssynchrony with survival benefit from revascularization: a study of gated positron emission tomography in patients with ischemic LV dysfunction and narrow QRS.

PURPOSE: LV mechanical dyssynchrony (LVMD) is a risk marker in narrow QRS cardiomyopathy, but its association with treatment outcome is not well defined. We determined the incremental prognostic value of LVMD in ischemic cardiomyopathy, and assessed its interaction with scar, myocardium in jeopardy and subsequent revascularization. METHODS: Stress and rest (82)Rb gated PET were performed in 486 consecutive patients (66 ± 11 years of age, 82 % men, LV ejection fraction 26 ± 6 %) with ischemic cardiomyopathy and QRS <120 ms. LVMD was determined as the standard deviation (SD) of the regional time to minimum volume on phase analysis of the gated PET scan. A propensity score was determined to adjust for nonrandomized referral after imaging to coronary artery bypass grafting (CABG). In a Cox proportional hazards model used to determine the association between measures of LVMD and survival time, CABG was included as a time-dependent covariate and the use of an implantable cardiac defibrillator (ICD) after imaging was modeled as a stratification factor. RESULTS: Over 1.9 ± 1.4 years, 96 patients (20 %) underwent CABG and 108 (22 %) died. LVMD was a predictor of mortality (HR 1.16. 95 % CI 1.03;1.30, per 10° increase in phase SD, p = 0.02) after adjusting for baseline covariates, prior ICD use, the use of postimaging CABG, and other imaging data. There was a significant interaction between phase SD and CABG. Nested Cox models showed that LVMD carried prognostic information incremental to clinical variables, ejection fraction and CABG. CONCLUSION: LVMD is an independent predictor of all-cause mortality in ischemic cardiomyopathy, and may identify patients with a differential survival benefit from CABG versus medical therapy.

Effect of tracer dose on left ventricular mechanical dyssynchrony indices by phase analysis of gated single photon emission computed tomography myocardial perfusion imaging.

BACKGROUND: There are limited data on the effect of tracer dose on the reproducibility and accuracy of left ventricular (LV) mechanical dyssynchrony indices by phase analysis of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS AND RESULTS: We measured LV dyssynchrony in 54 patients with normal LV ejection and perfusion (group 1) and 54 age and gender matched patients with LV ejection <35% (group 2) using phase analysis of gated SPECT MPI from stress (high dose) and rest (low dose) studies with 2 software programs: Corridor4DM (4DM) and Emory Cardiac Toolbox (ECTb). Although the correlation between rest- and stress-derived standard deviation was good (R = 0.76, P < .0001, with both software programs), there was considerable variability between the measurements (P < .0001 by paired t test). In addition, the rest standard deviation was significantly higher than stress in group 1 (10.2° ± 4.6° vs 6.1° ± 2.5°, and 12.2° ± 6.4° vs 7.9° ± 4.6°, with 4DM and ECTb, respectively, P < .0001 for both) and group 2 patients (44.0° ± 18.0° vs 35.9° ± 21.0° and 47.3° ± 19.2° vs 38.8° ± 19.8°, with 4DM and ECTb, P = .03 and .02, respectively). Similarly, the rest standard deviations were higher than the stress values irrespective of the type of stress test (i.e., exercise vs pharmacological), and the body mass index. Finally, using rest-derived dyssynchrony indices was associated with 9%-13% and 22%-26% false positive rate of significant mechanical dyssynchrony using different cut-off values for groups 1 and 2, respectively. CONCLUSION: LV mechanical dyssynchrony indices by phase analysis have more variation and are significantly higher if derived from rest gated SPECT images obtained with low-dose tracer.

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.

Developing an action plan for patient radiation safety in adult cardiovascular medicine. Proceedings from the Duke University Clinical Research Institute/American College of Cardiology Foundation/American Heart Association Think Tank Held on February 28, 2011.

Technological advances and increased utilization of medical testing and procedures have prompted greater attention to ensuring the patient safety of radiation use in the practice of adult cardiovascular medicine. In response, representatives from cardiovascular imaging societies, private payers, government and nongovernmental agencies, industry, medical physicists, and patient representatives met to develop goals and strategies toward this end; this report provides an overview of the discussions. This expert "think tank" reached consensus on several broad directions including: the need for broad collaboration across a large number of diverse stakeholders; clarification of the relationship between medical radiation and stochastic events; required education of ordering and providing physicians, and creation of a culture of safety; development of infrastructure to support robust dose assessment and longitudinal tracking; continued close attention to patient selection by balancing the benefit of cardiovascular testing and procedures against carefully minimized radiation exposures; collation, dissemination, and implementation of best practices; and robust education, not only across the healthcare community but also to patients, the public, and media. Finally, because patient radiation safety in cardiovascular imaging is complex, any proposed actions need to be carefully vetted (and monitored) for possible unintended consequences.