18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

Hot spot imaging in cardiovascular diseases: an information statement from SNMMI, ASNC, and EANM.

This information statement from the Society of Nuclear Medicine and Molecular Imaging, American Society of Nuclear Cardiology, and European Association of Nuclear Medicine describes the performance, interpretation, and reporting of hot spot imaging in nuclear cardiology. The field of nuclear cardiology has historically focused on cold spot imaging for the interpretation of myocardial ischemia and infarction. Hot spot imaging has been an important part of nuclear medicine, particularly for oncology or infection indications, and the use of hot spot imaging in nuclear cardiology continues to expand. This document focuses on image acquisition and processing, methods of quantification, indications, protocols, and reporting of hot spot imaging. Indications discussed include myocardial viability, myocardial inflammation, device or valve infection, large vessel vasculitis, valve calcification and vulnerable plaques, and cardiac amyloidosis. This document contextualizes the foundations of image quantification and highlights reporting in each indication for the cardiac nuclear imager.

Metabolic heterogeneous zone assessed by 18 FDG-PET is predictive of postablation mortality in patients with ventricular tachycardia.

PURPOSE: We sought to study the predictive value of the metabolic heterogeneous zone (HZ) as determined by 18 Fluorodeoxyglucose (18 FDG) positron emission tomography (PET) viability studies in ventricular tachycardia (VT) patients. METHODS: PET studies utilizing 82 Rubidium (82 Rb) tracer for perfusion and 18 FDG tracer for viability were analyzed using PMOD (PMOD Technologies) and further analyzed using 684-segment plots. 18 FDG uptake was normalized to the area with maximal perfusion on the rest 82 Rb study. Metabolic scar, HZ, and healthy segments were defined with perfusion-normalized 18 FDG uptake between 0%-50%, 50%-70%, and >70%, respectively. RESULTS: Thirty-four VT patients (age, 63 ± 12 years) were evaluated with 18 FDG-PET viability study. Most (n = 31) patients underwent VT ablation. Patients were categorized to HZ < median versus HZ ≥ median based on a median HZ area size of 21.0 cm2 . HZ size was significantly larger in the deceased group than the alive group (35.2 cm2 vs. 18.1 cm2 , p = .01). Deaths were significantly higher in HZ ≥ 21 cm2 group than HZ < 21 cm2 group (58.8% vs. 11.8%, p = .005). Survival analysis showed significantly higher mortality in the HZ ≥ 21 cm2 group than the HZ < 21 cm2 group (HR = 4.1, 95% CI: 1.3-12.6, p = .016). In a multivariable analysis, HZ was found to be an independent predictor for all-cause mortality (HR = 1.07, 95% CI: 1.02-1.12, p = .01) CONCLUSIONS: Increased HZ size of myocardium was associated with increased mortality. Metabolic HZ quantification may be of value in risk stratification and management of ischemic and nonischemic patients with VT.

Incremental Value of FDG-PET in the Evaluation of Cardiac Masses.

PURPOSE OF REVIEW: This study aims to review the various roles and evidence underlying the use of fluorodeoxyglucose (FDG) PET/CT and PET/MR for the assessment of cardiac masses. RECENT FINDINGS: The role of FDG-PET for the evaluation of cardiac masses continues to evolve. Studies have shown that FDG-PET is particularly well-suited for differentiating malignant from benign cardiac lesions based on their metabolic activity. Furthermore, FDG-PET is uniquely positioned to investigate patients with cardiac mass as most malignant cardiac lesions are metastasis. Finally, FDG-PET enables staging of patients with primary malignant cardiac tumor, identification of potential biopsy site, and planning of radiotherapy. FDG-PET is a complementary tool for the evaluation of patients with cardiac mass and can help differentiate benign from malignant lesions, as well as provide whole-body staging.

Potential Cardiac Amyloid PET/CT Imaging Targets for Differentiating Immunoglobulin Light Chain From Transthyretin Amyloidosis.

PURPOSE OF THE REVIEW: Cardiac involvement in amyloidosis plays a critical role in the clinical manifestation and prognostication. Since advanced treatment options for immunoglobulin light chains (AL) or liver-generated protein transthyretin (TTR) are quite different, a non-invasive and comprehensive imaging approach for the identification and characterization of these forms of cardiac amyloidosis is warranted. RECENT FINDINGS: Various 18Flabeled radiotracers and positron emission tomography (PET) imaging have been appreciated as a as a valid and non-invasive diagnostic approach to identify and quantify disease activity of cardiac amyloidosis. Interestingly, applying 18F-florbetapen and delayed PET imaging may even afford the possibility to not only detect cardiac amyloidosis but also to reliably differentiate between AL and TTR, respectively. This review summarizes contributions of cardiac PET imaging for the non-invasive identification and potential differentiation between AL and TTR amyloidosis that likely holds promise to gear medical treatment in the individual patient for an improved outcome.

Microvascular Angina Diagnosed by Absolute PET Myocardial Blood Flow Quantification.

PURPOSE OF REVIEW: The aim of this review is to provide an update on the use of positron emission tomography (PET) with myocardial blood flow (MBF) quantification for the diagnosis and management of patients with microvascular disease. RECENT FINDINGS: It is now recognized that a large proportion of patients with classical angina and non-obstructive epicardial disease are suffering from microvascular angina. Microvascular angina shares several key features with epicardial coronary disease, including many risk factors. Clinical criteria for the diagnosis of microvascular angina were recently proposed and PET imaging is called to play a central role in evaluation of these patients. Indeed, PET allows non-invasive measurements of MBF and flow reserve, which are altered in microvascular dysfunction. Furthermore, PET with flow quantification provides independent prognostic information and has the potential to monitor response to therapy in microvascular disease. PET with MBF quantification allows detection of microvascular dysfunction and plays a key role in the investigation of patients with suspected microvascular angina.

Detection of Native and Prosthetic Valve Endocarditis: Incremental Attributes of Functional FDG PET/CT over Morphologic Imaging.

PURPOSE OF REVIEW: The clinical and incremental value of functional imaging with 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) for the diagnosis and management of patients with suspected native and prosthetic valve infective endocarditis (IE). RECENT FINDINGS: The diagnosis of IE is challenging because of the highly variable clinical presentations, especially in the case of prosthetic valve endocarditis (PVE). FDG PET/CT has been shown to play an important role for the diagnosis of PVE as a major Duke criterion. Whether FDG PET/CT could play a similar role in patients with suspected native valve endocarditis (NVE) is less well established. It is increasingly recognized that IE is a multisystem disorder, and identification of extra-cardiac manifestations on whole-body FDG PET/CT impacts management and prognosis of patients with IE. Finally, FDG PET/CT provides incremental prognostic value over other clinical and para-clinical parameters, enabling prediction of in-hospital mortality, IE recurrence, hospitalization, and new onset heart failure and embolic events. FDG PET/CT plays a key role in the investigation of patients with suspected IE, enabling detection of valvular infection and extra-cardiac manifestations of the infection which has important prognostic implications.

Myocardial Viability: Survival Mechanisms and Molecular Imaging Targets in Acute and Chronic Ischemia.

Myocardial responses to acute ischemia/reperfusion and to chronic ischemic conditions have been studied extensively at all levels of organization. These include subcellular (eg, mitochondria in vitro); intact, large animal models (eg, swine with chronic coronary stenosis); as well as human subjects. Investigations in humans have used positron emission tomographic metabolic and myocardial blood flow measurements, assessment of gene expression and anatomic description of myocardium obtained at the time of coronary artery revascularization, ventricular assist device placement, or heart transplantation. A multitude of genetic, molecular, and metabolic pathways have been identified, which may promote either myocyte survival or death or, most interestingly, both. Many of these potential mediators in both acute ischemia/reperfusion and adaptations to chronic ischemic conditions involve the mitochondria, which play a central role in cellular energy production and homeostasis. The present review is focused on operative survival mechanisms and potential myocardial viability molecular imaging targets in acute and chronic ischemia, especially those which impact mitochondrial function.

Aminophylline shortage and current recommendations for reversal of vasodilator stress: An ASNC information statement endorsed by SCMR.

Pharmacologic reversal of serious or intolerable side effects (SISEs) from vasodilator stress is an important safety and comfort measure for patients experiencing such effects. While typically performed using intravenous aminophylline, recurrent shortages of this agent have led to a greater need to limit its use and consider alternative agents. This information statement provides background and recommendations addressing indications for vasodilator reversal, timing of a reversal agent, incidence of observed SISE with vasodilator stress, clinical and logistical considerations for aminophylline-based reversal, and alternative non-aminophylline based reversal protocols.

The Cardiorenal Axis: Myocardial Perfusion, Metabolism, and Innervation.

PURPOSE OF THE REVIEW: Cardiorenal syndrome (CRS), defined as concomitant heart and kidney disease, has been a focus of attention for nearly a decade. As more patients survive severe acute and chronic heart and kidney diseases, CRS has emerged as an "epidemic" of modern medicine. Significant advances have been made in unraveling the complex mechanisms that underlie CRS based on classification of the condition into five pathophysiologic subtypes. In types 1 and 2, acute or chronic heart disease results in renal dysfunction, while in types 3 and 4, acute or chronic kidney diseases are the inciting factors for heart disease. Type 5 CRS is defined as concomitant heart and kidney dysfunction as part of a systemic condition such as sepsis or autoimmune disease. RECENT FINDINGS: There are ongoing efforts to better define subtypes of CRS based on historical information, clinical manifestations, laboratory data (including biomarkers), and imaging characteristics. Systematic evaluation of CRS by advanced cardiac imaging, however, has been limited in scope and mostly focused on type 4 CRS. This is in part related to lack of clinical trials applying advanced cardiac imaging in the acute setting and exclusion of patients with significant renal disease from studies of such techniques in chronic HF. Advanced cardiac nuclear imaging is well poised for assessment of the pathophysiology of CRS by offering a myriad of molecular probes without the need for nephrotoxic contrast agents. In this review, we examine the current or potential future application of advanced cardiac imaging to evaluation of myocardial perfusion, metabolism, and innervation in patients with CRS.

Novel Myocardial PET/CT Receptor Imaging and Potential Therapeutic Targets.

PURPOSE OF THE REVIEW: Activation of myocardial cannabinoid type 1 receptors (CB1-R) and/or angiotensin II type 1 receptors (AT1-R) likely plays an important mechanistic role in determining the left-ventricular remodeling process in systolic heart failure. We provide an overview on novel radiotracer probes and positron emission tomography (PET)/computed tomography (CT) imaging to noninvasively probe the expression of myocardial CB1-R and/or AT1-R. RECENT FINDINGS: Recent translational investigations have demonstrated the feasibility of 11C-OMAR or 11C-KR31173 and PET/CT to image and quantify myocardial CB1-R and/or AT1-R expression, respectively. There is an increasing understanding of the mechanisms of activated myocardial CB1-R and/or AT1-R to influence the left-ventricular remodeling process in systolic heart failure in different disease entities. The review summarizes contributions of PET to image myocardial CB1-R and AT1-R expression that may have the potential to serve as a target to tailor preventive medical care in the individual patient.

Aminophylline shortage and current recommendations for reversal of vasodilator stress: an ASNC information statement endorsed by SCMR.

Pharmacologic reversal of serious or intolerable side effects (SISE) from vasodilator stress is an important safety and comfort measure for patients experiencing such effects. While typically performed using intravenous aminophylline, recurrent shortages of this agent have led to a greater need to limit its use and consider alternative agents. This information statement provides background and recommendations addressing indications for vasodilator reversal, timing of a reversal agent, incidence of observed SISE with vasodilator stress, clinical and logistical considerations for aminophylline-based reversal, and alternative non-aminophylline based reversal protocols.

The effect of time-of-flight and point spread function modeling on 82Rb myocardial perfusion imaging of obese patients.

BACKGROUND: The effect of time-of-flight (TOF) and point spread function (PSF) modeling in image reconstruction has not been well studied for cardiac PET. This study assesses their separate and combined influence on 82Rb myocardial perfusion imaging in obese patients. METHODS: Thirty-six obese patients underwent rest-stress 82Rb cardiac PET. Images were reconstructed with and without TOF and PSF modeling. Perfusion was quantitatively compared using the AHA 17-segment model for patients grouped by BMI, cross-sectional body area in the scanner field of view, gender, and left ventricular myocardial volume. Summed rest scores (SRS), summed stress scores (SSS), and summed difference scores (SDS) were compared. RESULTS: TOF improved polar map visual uniformity and increased septal wall perfusion by up to 10%. This increase was greater for larger patients, more evident for patients grouped by cross-sectional area than by BMI, and more prominent for females. PSF modeling increased perfusion by about 1.5% in all cardiac segments. TOF modeling generally decreased SRS and SSS with significant decreases between 2.4 and 3.0 (P < .05), which could affect risk stratification; SDS remained about the same. With PSF modeling, SRS, SSS, and SDS were largely unchanged. CONCLUSION: TOF and PSF modeling affect regional and global perfusion, SRS, and SSS. Clinicians should consider these effects and gender-dependent differences when interpreting 82Rb perfusion studies.

Myocardial perfusion imaging: Lessons learned and work to be done-update.

As the second term of our commitment to Journal begins, we, the editors, would like to reflect on a few topics that have relevance today. These include prognostication and paradigm shifts; Serial testing: How to handle data? Is the change in perfusion predictive of outcome and which one? Ischemia-guided therapy: fractional flow reserve vs perfusion vs myocardial blood flow; positron emission tomography (PET) imaging using Rubidium-82 vs N-13 ammonia vs F-18 Flurpiridaz; How to differentiate microvascular disease from 3-vessel disease by PET? The imaging scene outside the United States, what are the differences and similarities? Radiation exposure; Special issues with the new cameras? Is attenuation correction needed? Are there normal databases and are these specific to each camera system? And finally, hybrid imaging with single-photon emission tomography or PET combined with computed tomography angiography or coronary calcium score. We hope these topics are of interest to our readers.

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.

Clinical Phenotyping of Transthyretin Cardiac Amyloidosis with Bone-Seeking Radiotracers in Heart Failure with Preserved Ejection Fraction.

PURPOSE OF REVIEW: The two most common types of cardiac amyloidosis are caused by fibril deposits of immunoglobulin light chains (AL) and transthyretin (TTR), each with distinct prognosis and clinical management. Cardiac amyloidosis is under-recognized among heart failure patients with preserved ejection fraction (HFpEF). Bone-seeking tracers like 99mTc-PYP and 99mTc-DPD have long been used to identify cardiac amyloidosis, and more recently, to differentiate TTR from AL cardiac amyloidosis in symptomatic patients. However, results are mainly derived from single-center retrospective studies, with comparable but not standardized imaging protocols and interpretation criteria. RECENT FINDINGS: The clinical scope of cardiac amyloidosis among HFpEF patients and current literature supporting the use of bone-seeking tracers for TTR cardiac amyloidosis are presented. The differences of imaging techniques for cardiac amyloid and bone disease evaluation, bone tracer pharmacodynamics, and imaging interpretation criteria for cardiac amyloidosis diagnosis are discussed. Finally, a diagnostic algorithm to use bone scintigraphy in cardiac amyloidosis diagnosis among HFpEF patients is proposed. Bone scintigraphy with 99mTc-PYP or 99mTc-DPD can be a useful tool with high sensitivity and specificity for detecting TTR-related cardiac amyloidosis in patients with HFpEF. It is needed to standardize the imaging protocol and interpretation criteria and to perform prospective clinical studies.

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

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

Science to Practice: Does FDG Differentiate Morphologically Unstable from Stable Atherosclerotic Plaque?

It has been reported that fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) may detect the inflammatory state and macrophage burden of atherosclerotic plaques and potentially identify vulnerable plaques. However, published reports have been inconsistent in this area. Tavakoli et al ( 1 ) hypothesized that differential regulation of macrophage glucose metabolism by macrophage colony-stimulating factor (M-CSF; inflammation resolving) and granulocyte-M-CSF (GM-CSF; proinflammatory) may contribute to the inconsistency of FDG vessel wall inflammation. After the induction of inflammatory and metabolic profiles, both M-CSF and GM-CSF generated comparable levels of glucose uptake in cultured macrophages and murine atherosclerotic plaques. These findings suggest that although FDG uptake is an indicator of vascular macrophage burden (total number of macrophages), it may not necessarily differentiate morphologically unstable (inflammatory) from stable (noninflammatory) atherosclerotic plaque. Moreover, although atherosclerosis is characterized by macrophage-predominated inflammation, there is a wide range of other vascular diseases in which macrophages and inflammation play an important role in the absence of atherosclerosis. FDG uptake will be indistinguishable in atherosclerosis from large-artery inflammatory vascular disease, such as Takayasu arteritis, chemotherapy- or radiation-induced vascular inflammation, or foreign-body reaction, such as synthetic arterial graft. Because of the nonspecific nature of FDG uptake by any cell (upregulated under hypoxic conditions or other microenvironmental factors), this work calls for a more cautious approach to interpreting vascular FDG uptake as indicative of inflammatory atherosclerosis in the clinical setting.