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.

Regional Variation in Technetium Pyrophosphate Uptake in Transthyretin Cardiac Amyloidosis and Impact on Mortality.

OBJECTIVES: This study sought to investigate the regional uptake of technetium 99m-pyrophosphate (TcPYP) in transthyretin cardiac amyloidosis (ATTR) and its association with mortality. BACKGROUND: TcPYP nuclear scintigraphy is a diagnostic and prognostic tool in ATTR. Echocardiography has identified a pattern of regional variation in longitudinal strain (LS) with a gradient of improved strain from base to apex in ATTR. METHODS: Consecutive patients with ATTR were evaluated who underwent TcPYP nuclear scintigraphy with planar and attenuation corrected single-photon emission computed tomography (SPECT). Heart-to-contralateral lung (H/CL) ratio was calculated on planar images, and left ventricular (LV) uptake was determined in each of the 17 segments using SPECT. A measure of apical-sparing of myocardial TcPYP uptake, termed the apical-sparing ratio (ASR), was calculated as basal + mid / apical counts. RESULTS: Overall, 54 patients with ATTR (age 78 ± 9 years, 76% male, 31% hereditary ATTR) were analyzed. There was increased TcPYP uptake in basal and mid relative to apical LV segments, and an apical-sparing LS pattern on echocardiography. The right ventricle similarly showed greater uptake in basal segments. There were 26 deaths over 1.8 years median follow-up. The ASR of TcPYP uptake was associated with age-adjusted all-cause mortality (p = 0.013) with worse prognosis seen at levels <2.75. Global LS was also prognostic (p = 0.01), whereas H/CL ratio and total LV uptake indexed to blood pool were not (p = 0.772 and p = 0.850, respectively). The prognostic utility of the ASR persisted in multivariable modeling (p = 0.003), whereas global LS did not. CONCLUSIONS: There is decreased TcPYP uptake in apical as compared to mid and basal segments in the LV, mimicking apical-sparing LS seen on echocardiography. Regional distribution of LV TcPYP uptake is associated with mortality, whereas overall amount of uptake as measured by H/CL ratio and indexed LV SPECT uptake is not.

ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities. Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines. A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario. The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will improve and standardize physician decision making. AUC publications reflect an ongoing effort by the American College of Cardiology to critically and systematically create, review, and categorize clinical situations where diagnostic tests and procedures are utilized by physicians caring for patients with cardiovascular diseases. The process is based on the current understanding of the technical capabilities of the imaging modalities examined.

Prognostic Impact of Extent, Severity, and Heterogeneity of Abnormalities on 18F-FDG PET Scans for Suspected Cardiac Sarcoidosis.

OBJECTIVES: This study sought to evaluate the incremental value of quantifying the extent and severity of myocardial perfusion and 18F-labeled fluorodeoxyglucose (FDG) abnormalities in predicting adverse outcomes among patients with suspicion for cardiac sarcoidosis (CS). BACKGROUND: Positron emission tomography (PET) with FDG is a key component of the noninvasive assessment of patients with suspected CS. However, the optimal method for image interpretation has not been defined. METHODS: A retrospective analysis was performed of 203 patients who underwent perfusion and FDG-PET imaging to evaluate for CS. Imaging findings were scored by conventional 3-category methods (normal perfusion and metabolism, abnormal perfusion or metabolism, abnormal perfusion and metabolism) and by summed scores using the 17-segment model to represent extent and severity of disease. Heterogeneity of metabolism was quantified using the coefficient of variation (SD divided by the mean) of FDG uptake. Multivariable Cox models were developed to assess associations between imaging findings and adverse events (death, heart transplant, or ventricular arrhythmia requiring defibrillation). RESULTS: The indication for FDG-PET was ventricular arrhythmia in 69 (34%), heart block in 16 (8%), cardiomyopathy in 54 (27%), and other indications in 64 (32%). There were 63 patients who developed adverse events over a mean follow-up of 1.8 years. After robust adjustment, only the summed score in segments with a perfusion-metabolism mismatch and the coefficient of variation were important prognostically (p = 0.029 and p = 0.041, respectively). CONCLUSIONS: Quantitative measures of extent and severity of perfusion-metabolism mismatch and coefficient of variation of FDG uptake provide an incremental prognostic advantage in patients undergoing FDG-PET for CS. These results support the use of a more detailed analysis of imaging findings, as is conventional in coronary artery disease.

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.

The Future of Cardiac Imaging: Report of a Think Tank Convened by the American College of Cardiology.

The American College of Cardiology's Executive Committee and Cardiovascular Imaging Section Leadership Council convened a discussion regarding the future of cardiac imaging among thought leaders in the field during a 2 day Think Tank. Participants were charged with thinking broadly about the future of imaging and developing a roadmap to address critical challenges. Key areas of discussion included: 1) how can cardiac imaging services thrive in our new world of value-based health care? 2) Who is the cardiac imager of the future and what is the role of the multimodality imager? 3) How can we nurture innovation and research in imaging? And 4) how can we maximize imaging information and optimize outcomes? This document describes the proceedings of this Think Tank.

Predicting Risk Versus Predicting Potential Survival Benefit Using 123I-mIBG Imaging in Patients With Systolic Dysfunction Eligible for Implantable Cardiac Defibrillator Implantation: Analysis of Data From the Prospective ADMIRE-HF Study.

BACKGROUND: Cardiac (123)I-metaiodobenzylguanidine ((123)I-mIBG) imaging improves prognostication in patients with left ventricular (LV) dysfunction. Whether (123)I-mIBG can identify optimal candidates for implantable cardiac defibrillator (ICD) placement is unclear. We examined whether (123)I-mIBG enhances risk assessment and identifies patients with enhanced survival with ICD in a patient cohort with reduced LV function who were candidates for ICD implantation. METHODS AND RESULTS: We identified 777 patients (66 sites, 12 countries) without ICD at the time of enrollment in Adreview Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) and index (123)I-mIBG study. Patients completed prescribed study protocol and follow-up. Heart-to-mediastinum (H/M) ratio was determined from (123)I-mIBG results. Survival modeling used a Cox proportional hazards mixed-effects model, including a propensity score, to adjust for nonrandomized ICD implantation after (123)I-mIBG. All-cause death occurred in 75 patients (9.6%), and 196 (25%) patients had ICD implantation on follow-up. After adjusting for multiple factors, although the H/M ratio added incremental prognostic value and enhanced reclassification, neither H/M results, BNP levels, nor left ventricular ejection fraction interacted with ICD use in the survival model, indicating that these variables did not identify patients with enhanced survival with ICD implantation. Nonetheless, H/M results did identify the number of lives saved by ICD use per 100 treated. CONCLUSIONS: We found that although (123)I-mIBG imaging enhances the risk stratification of patients with left ventricular dysfunction who are ICD candidates, it does not identify which patients may have improved survival with ICD placement. However, (123)I-mIBG identifies the absolute benefit gained with ICD use, thus may play a role in optimizing the cost-effectiveness of this intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00126425 and NCT00126438.

¹²³I-MIBG Imaging for Prediction of Mortality and Potentially Fatal Events in Heart Failure: The ADMIRE-HFX Study.

UNLABELLED: ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) established the prognostic significance of (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging in heart failure subjects (median follow-up, 17 mo) using a composite endpoint dominated by heart failure progression. The ADMIRE-HF extension (ADMIRE-HFX) extended follow-up to a median of 24 mo and used mortality as the primary endpoint. The objective of these analyses was to use multiple multivariate risk modeling techniques to determine the independent predictive ability of (123)I-MIBG imaging for mortality outcomes. METHODS: Data from 964 New York Heart Association class II-III subjects in ADMIRE-HFX were included. All-cause mortality and a composite endpoint of death or death-equivalent events (resuscitated arrest, successful defibrillation for ventricular tachycardia or ventricular fibrillation) were analyzed with multivariate Cox proportional hazards and logistic regression techniques using demographic and clinical variables and the (123)I-MIBG heart-to-mediastinum ratio (H/M). The incremental value of H/M was also examined for the logistic regression models using receiver-operating-characteristic curve methods and for the proportional hazards models using net reclassification improvement. RESULTS: There were 101 deaths, and 136 subjects had a composite event during follow-up. H/M was significant in all multivariate proportional hazards and logistic regression models for the 2 mortality endpoints, both models developed with only clinical variables and those including left ventricular ejection fraction and b-type natriuretic peptide (BNP). For baseline models including BNP, the addition of H/M did not significantly increase receiver-operating-characteristic curve area. However, there was significant net reclassification improvement with the addition of H/M to a proportional hazards model containing BNP and left ventricular ejection fraction. CONCLUSION: The multivariate Cox proportional hazards and logistic regression analyses demonstrated consistent significance for H/M when added to the baseline risk models for mortality and mortality-equivalent events.

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.