Use of cardiac radionuclide imaging to identify patients at risk for arrhythmic sudden cardiac death.

Kelesidis I, Travin MI
Sudden cardiac death (SCD) accounts for about ½ of all cardiovascular deaths, in most cases the result of a lethal ventricular arrhythmia. Patients considered at risk are often treated with an implantable cardiac defibrillator (ICD), but current criteria for device use, based largely on left ventricular ejection fraction (LVEF), leads to many patients receiving ICDs that they do not use, and many others not receiving ICDs but who suffer SCD. Thus, better methods of identifying patients at risk for SCD are needed, and radionuclide imaging offers much potential. Recent work has focused on imaging of cardiac autonomic innervation. (123)I-mIBG, a norepinephrine analog, is the tracer most studied, and a variety of positron emission tomographic tracers are also under investigation. Radionuclide autonomic imaging may identify at-risk patients with ischemic coronary artery disease, particularly following myocardial infarction and in the setting of hibernating myocardium. Most studies have been done in the setting of congestive heart failure (CHF), with a recent large multicenter study of patients with advanced disease, typically at high risk of SCD, showing that (123)I-mIBG can identify a low risk subgroup with an extremely low incidence of lethal ventricular arrhythmias and cardiac death, therefore, perhaps not requiring an ICD. Cardiac neuronal imaging has been shown to be better predictive of lethal arrhythmias/cardiac death than LVEF and New York Heart Association class, as well as various ECG parameters. Autonomic imaging will likely play an important role in the advancement of cardiac molecular imaging.

J Nucl Cardiol: 01 Dec 2011; epub ahead of print

PET/MR: Yet another Tesla?

Schwaiger M, Kunze K, Rischpler C, Nekolla SG
After the successful introduction of PET/CT as a multimodality imaging technique, PET/MR has subsequently emerged as an attractive instrumentation for applications in neurology, oncology, and cardiology. Simultaneous data acquisition combining structural, functional, and molecular imaging provides a unique platform to link various aspects of cardiac performance for the non-invasive characterization of cardiovascular disease phenotypes. Specifically, tissue characterization by MR techniques with and without contrast agents allows for functional parameters such as LGE, myocardial perfusion, and T1 maps as well as an estimate of extracellular volume. PET tracers excel by their high sensitivity and specificity, thus supplementing the functional tissue characterization by MRI. Although the clinical applications are yet to be validated , the first experience with PET/MR suggests future applications in the area of vascular imaging (unstable plaque) as well as in the characterization of inflammatory processes involving the heart. Ischemic heart disease can be comprehensively assessed by integrating regional function, perfusion, and viability. Future technical improvements leading to less costly PET/MR instrumentation are necessary to support routine clinical application of this promising technique in cardiology.

J Nucl Cardiol: 22 Sep 2016; epub ahead of print

The role of positron emission tomography in the evaluation of myocardial ischemia in women.

Taqueti VR, Dorbala S
Cardiovascular disease continues to be the number one cause of death in women, yet most women are unaware of their risk. Over the last decade, radionuclide myocardial perfusion imaging with positron emission tomography (PET) has become a powerful tool for the diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). This editorial viewpoint will review the maturing role of PET imaging in women, particularly as applied to the evaluation of ischemic heart disease. Specifically, we focus on distinct advantages offered by PET imaging in the evaluation of myocardial ischemia in women: (1) improved diagnostic accuracy, including in the presence of breast or adipose tissue and small left ventricular cavity size, (2) decreased radiation exposure through the use of short-lived radiopharmaceuticals, and (3) the ability to quantify myocardial blood flow and coronary flow reserve to diagnose ischemia, even in the absence of obstructive CAD. As such, cardiac PET perfusion imaging stands to play a unique role in defining the diagnosis and prognosis of women with ischemic heart disease, while also guiding new treatment strategies for their more prevalent cardiovascular disease phenotypes.

J Nucl Cardiol: 03 Aug 2016; epub ahead of print

Principles and techniques of imaging in identifying the substrate of ventricular arrhythmia.

Rijnierse MT, Allaart CP, Knaapen P
Life-threatening ventricular arrhythmias (VA) are a major cause of death in patients with cardiomyopathy. To date, impaired left ventricular ejection fraction remains the primary criterion for implantable cardioverter-defibrillator therapy to prevent sudden cardiac death. In recent years, however, advanced imaging techniques such as nuclear imaging, cardiac magnetic resonance imaging, and computed tomography have allowed for a more detailed evaluation of the underlying substrate of VA. These imaging modalities have emerged as a promising approach to assess the risk of sudden cardiac death. In addition, non-invasive identification of the critical sites of arrhythmias may guide ablation therapy. Typical anatomical substrates that can be evaluated by multiple advanced imaging techniques include perfusion abnormalities, scar and its border zone, and sympathetic denervation. Understanding the principles and techniques of different imaging modalities is essential to gain more insight in their role in identifying the arrhythmic substrate. The current review describes the principles of currently available imaging techniques to identify the substrate of VA.

J Nucl Cardiol: 14 Dec 2015; epub ahead of print

Cardiac molecular imaging to track left ventricular remodeling in heart failure.

Shirani J, Singh A, Agrawal S, Dilsizian V
Cardiac left ventricular (LV) remodeling is the final common pathway of most primary cardiovascular diseases that manifest clinically as heart failure (HF). The more advanced the systolic HF and LV dysfunction, the worse the prognosis. The knowledge of the molecular, cellular, and neurohormonal mechanisms that lead to myocardial dysfunction and symptomatic HF has expanded rapidly and has allowed sophisticated approaches to understanding and management of the disease. New therapeutic targets for pharmacologic intervention in HF have also been identified through discovery of novel cellular and molecular components of membrane-bound receptor-mediated intracellular signal transduction cascades. Despite all advances, however, the prognosis of systolic HF has remained poor in general. This is, at least in part, related to the (1) relatively late institution of treatment due to reliance on gross functional and structural abnormalities that define the "heart failure phenotype" clinically; (2) remarkable genetic-based interindividual variations in the contribution of each of the many molecular components of cardiac remodeling; and (3) inability to monitor the activity of individual pathways to cardiac remodeling in order to estimate the potential benefits of pharmacologic agents, monitor the need for dose titration, and minimize side effects. Imaging of the recognized ultrastructural components of cardiac remodeling can allow redefinition of heart failure based on its "molecular phenotype," and provide a guide to implementation of "personalized" and "evidence-based" evaluation, treatment, and longitudinal monitoring of the disease beyond what is currently available through randomized controlled clinical trials.

J Nucl Cardiol: 01 Aug 2016; epub ahead of print

Traditional gamma cameras are preferred.

DePuey EG
Although the new solid-state dedicated cardiac cameras provide excellent spatial and energy resolution and allow for markedly reduced SPECT acquisition times and/or injected radiopharmaceutical activity, they have some distinct disadvantages compared to traditional sodium iodide SPECT cameras. They are expensive. Attenuation correction is not available. Cardio-focused collimation, advantageous to increase depth-dependent resolution and myocardial count density, accentuates diaphragmatic attenuation and scatter from subdiaphragmatic structures. Although supplemental prone imaging is therefore routinely advised, many patients cannot tolerate it. Moreover, very large patients cannot be accommodated in the solid-state camera gantries. Since data are acquired simultaneously with an arc of solid-state detectors around the chest, no temporally dependent "rotating" projection images are obtained. Therefore, patient motion can be neither detected nor corrected. In contrast, traditional sodium iodide SPECT cameras provide rotating projection images to allow technologists and physicians to detect and correct patient motion and to accurately detect the position of soft tissue attenuators and to anticipate associated artifacts. Very large patients are easily accommodated. Low-dose x-ray attenuation correction is widely available. Also, relatively inexpensive low-count density software is provided by many vendors, allowing shorter SPECT acquisition times and reduced injected activity approaching that achievable with solid-state cameras.

J Nucl Cardiol: 12 Apr 2016; epub ahead of print

Patient preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of inflammation.

Osborne MT, Hulten EA, Murthy VL, Skali H, ... DiCarli MF, Blankstein R
Although the number of clinical applications for fluorine-18 fluorodeoxyglucose ((18)F-FDG) cardiac positron emission tomography (PET) has continued to grow, there remains a lack of consensus regarding the ideal method of suppressing normal myocardial glucose utilization for image optimization. This review describes various patient preparation protocols that have been used as well as the success rates achieved in different studies. Collectively, the available literature supports using a high-fat, no-carbohydrate diet for at least two meals with a fast of 4-12 hours prior to (18)F-FDG PET imaging and suggests that isolated fasting for less than 12 hours and supplementation with food or drink just prior to imaging should be avoided. Each institution should adopt a protocol and continuously monitor its effectiveness with a goal to achieve adequate myocardial suppression in greater than 80% of patients.

J Nucl Cardiol: 08 Jun 2016; epub ahead of print

The prognostic value of non-perfusion variables obtained during vasodilator stress myocardial perfusion imaging.

Bajaj NS, Singh S, Farag A, El-Hajj S, ... Iskandrian AE, Hage FG
Myocardial perfusion imaging (MPI) is an established diagnostic test that provides useful prognostic data in patients with known or suspected coronary artery disease. In more than half of the patients referred for stress testing, vasodilator stress is used in lieu of exercise. Unlike exercise, vasodilator stress does not provide information on exercise and functional capacity, heart rate recovery, and chronotropy, and ECG changes are less frequent. These non-perfusion data provide important prognostic and patient management information. Further, event rates in patients undergoing vasodilator MPI are higher than in those undergoing exercise MPI and even in those with normal images probably due to higher pretest risk. However, there are a number of non-perfusion variables that are obtained during vasodilator stress testing, which have prognostic relevance but their use has not been well emphasized. The purpose of this review is to summarize the prognostic values of these non-perfusion data obtained during vasodilator MPI.

J Nucl Cardiol: 03 Mar 2016; epub ahead of print

The role of nuclear cardiac imaging in risk stratification of sudden cardiac death.

Juneau D, Erthal F, Chow BJ, Redpath C, ... Knuuti J, Beanlands RS
Sudden cardiac death (SCD) represents a significant portion of all cardiac deaths. Current guidelines focus mainly on left ventricular ejection fraction (LVEF) as the main criterion for SCD risk stratification and management. However, LVEF alone lacks both sensitivity and specificity in stratifying patients. Recent research has provided interesting data which supports a greater role for advanced cardiac imaging in risk stratification and patient management. In this article, we will focus on nuclear cardiac imaging, including left ventricular function assessment, myocardial perfusion imaging, myocardial blood flow quantification, metabolic imaging, and neurohormonal imaging. We will discuss how these can be used to better understand SCD and better stratify patient with both ischemic and non-ischemic cardiomyopathy.

J Nucl Cardiol: 28 Jul 2016; epub ahead of print

Budget impact of applying appropriateness criteria for myocardial perfusion scintigraphy: The perspective of a developing country.

Dos Santos MA, Santos MS, Tura BR, Félix R, Brito AS, De Lorenzo A
Myocardial perfusion imaging is widely used for the risk stratification of coronary artery disease. In view of its cost, besides radiation issues, judicious evaluation of the appropriateness of its indications is essential to prevent an unnecessary economic burden on the health system. We evaluated, at a tertiary-care, public Brazilian hospital, the appropriateness of myocardial perfusion scintigraphy indications, and estimated the budget impact of applying appropriateness criteria. An observational, cross-sectional study of 190 patients with suspected or known coronary artery disease referred for myocardial perfusion imaging was conducted. The appropriateness of myocardial perfusion imaging indications was evaluated with the Appropriate Use Criteria for Cardiac Radionuclide Imaging published in 2009. Budget impact analysis was performed with a deterministic model. The prevalence of appropriate requests was 78%; of inappropriate indications, 12%; and of uncertain indications, 10%. Budget impact analysis showed that the use of appropriateness criteria, applied to the population referred to myocardial perfusion scintigraphy within 1 year, could generate savings of $ 64,252.04 dollars. The 12% inappropriate requests for myocardial perfusion scintigraphy at a tertiary-care hospital suggest that a reappraisal of MPI indications is needed. Budget impact analysis estimated resource savings of 18.6% with the establishment of appropriateness criteria for MPI.

J Nucl Cardiol: 26 May 2016; epub ahead of print

The role of treadmill exercise testing in women.

Acampa W, Assante R, Zampella E
Treadmill exercise electrocardiogram (ECG) is one of the most commonly used noninvasive tests for the assessment of ischemic heart disease (IHD). Sex-specific challenges in diagnostic and prognostic tests methods for IHD outlined the importance of pretest probability evaluation and referral bias using risk-prediction charts available for both asymptomatic and symptomatic women. Accordingly, exercise ECG has been indicated as the initial test for the symptomatic women at intermediate risk of IHD who has a normal resting ECG and is capable of maximal exercise. However, the difficulties of using exercise testing for diagnosing IHD in women have led to an initial speculation that stress imaging may be preferred to standard stress testing. This editorial analyzed a large body of evidence on the diagnostic and prognostic powers of treadmill ECG and exercise myocardial perfusion imaging (MPI) according to new advanced imaging technologies.

J Nucl Cardiol: 25 Jul 2016; epub ahead of print

Changing the trajectory of ischemic heart disease in women: Role of imaging.

Dorbala S, Shaw LJ
Mortality from coronary artery disease in women declined from nearly 500,000 deaths in 2000 to 398,096 deaths in 2013. Despite these significant gains, cardiovascular disease mortality in women remains unacceptably high. Much additional progress in awareness, evaluation, and management of cardiovascular diseases is needed. Progress in cardiovascular imaging, over the past four decades, has substantially improved the evaluation and management of ischemic heart disease. Ischemic heart disease is now diagnosed early and with greater accuracy, leading to improved risk assessment and timely therapies. The next gains in ischemic heart disease mortality in women will probably be due to application of these imaging advances in a personalized fashion. Thoughtful leaders provide their viewpoints on the use of imaging in the evaluation and management of ischemic heart disease in women.

J Nucl Cardiol: 25 Jul 2016; epub ahead of print

Absolute quantification of myocardial blood flow.

Yoshinaga K, Manabe O, Tamaki N
With the increasing availability of positron emission tomography (PET) myocardial perfusion imaging, the absolute quantification of myocardial blood flow (MBF) has become popular in clinical settings. Quantitative MBF provides an important additional diagnostic or prognostic information over conventional visual assessment. The success of MBF quantification using PET/computed tomography (CT) has increased the demand for this quantitative diagnostic approach to be more accessible. In this regard, MBF quantification approaches have been developed using several other diagnostic imaging modalities including single-photon emission computed tomography, CT, and cardiac magnetic resonance. This review will address the clinical aspects of PET MBF quantification and the new approaches to MBF quantification.

J Nucl Cardiol: 21 Jul 2016; epub ahead of print

The role of stress cardiac magnetic resonance in women.

Cardona A, Zareba KM, Raman SV
Coronary artery disease (CAD) is the leading cause of death in women. Nevertheless, extensive evidence demonstrates under-diagnosis and under-treatment of women for suspected or known ischemic heart disease (IHD). Stress cardiac magnetic resonance (CMR) is becoming readily available and offers significant advantages over other stress imaging modalities. The high spatial and temporal resolution of CMR provides the unique ability to identify subendocardial ischemia, viability, and the presence of microvascular disease. Furthermore, CMR is free from ionizing radiation, and image quality is not compromised by attenuation artifacts or patient size. Over the past two decades, evidence-based data have demonstrated the high diagnostic and prognostic performance of stress CMR in the context of IHD, often superior to other stress imaging techniques. Importantly, ad hoc studies confirmed these results in women with known or suspected IHD. Stress CMR warrants consideration as the modality of choice for women requiring an imaging test for ischemia given its strong evidence base, superior test characteristics, comprehensive nature, and unique ability to characterize both epicardial and microvascular disease.

J Nucl Cardiol: 25 Jul 2016; epub ahead of print

Myocardial perfusion of infarcted and normal myocardium in propofol-anesthetized minipigs using (82)Rubidium PET.

Rasmussen T, Follin B, Kastrup J, Christensen TE, ... Kjær A, Hasbak P
Cardiac Rubidium-82 ((82)Rb) positron-emission-tomography (PET) is a good method for quantification of myocardial blood flow in man. Quantification of myocardial blood flow in animals to evaluate new treatment strategies or to understand underlying disease is also of great interest but raises some challenges. Animals, which have been anesthetized during PET acquisition, might react differently to used stress medications, and therefore difficulties might exist while evaluating the resulting PET images using standard software packages from commercial vendors optimized for human hearts. Furthermore propofol, used for anesthesia, can influence myocardial perfusion and coronary flow reserve due to its vasorelaxant effect, and interactions might exist between propofol and used stress agents, potentially affecting the result of the examination. We present cardiac (82)Rb-PET studies performed in propofol-anesthetized minipigs with normal and infarcted myocardium stressed with both adenosine and dipyridamole. Despite the mentioned challenges, we were able to trace the small minipig heart with software designed for human cardiac PET and to achieve blood flow measurements comparable with results in humans with both adenosine and dipyridamole. We found dipyridamole to be a superior stress agent for this experimental setup. Finally, we were able to clearly identify the myocardial perfusion defect after an induced myocardial infarction.

J Nucl Cardiol: 01 Mar 2016; epub ahead of print

Life-Threatening Ventricular Arrhythmias: Current Role of Imaging in Diagnosis and Risk Assessment.

Malhotra S, Canty JM
Sudden cardiac arrest continues to be a major cause of death from cardiovascular disease but our ability to predict patients at the highest risk of developing lethal ventricular arrhythmias remains limited. Left ventricular ejection fraction is inversely related to the risk of sudden death but has a low sensitivity and specificity for the population at risk. Nevertheless, it continues to be the main variable considered in identifying patients most likely to benefit from implantable defibrillators to prevent sudden death. Imaging myocardial sympathetic innervation with PET and SPECT as well as imaging characteristics of myocardial infarcts using gadolinium-enhanced cardiac magnetic resonance are emerging as imaging modalities that may further refine patient selection beyond ejection fraction. This review will primarily focus on employing advanced imaging approaches to identify patients with left ventricular dysfunction that are most likely to develop lethal arrhythmias and benefit from inserting a primary prevention implantable cardiac defibrillator. While not yet tested in prospective studies, we will review risk prediction models incorporating quantitative imaging and biomarkers that have been developed that appear promising to identify those at highest risk of sudden death.

J Nucl Cardiol: 17 Jan 2016; epub ahead of print

Mechanisms of sudden cardiac death.

McElwee SK, Velasco A, Doppalapudi H
Sudden cardiac death (SCD) continues to be a major public health problem and is thought to account for almost half of all cardiac deaths. Cardiac arrest and SCD are most commonly due to ventricular arrhythmias. Most patients who suffer cardiac arrest have underlying structural heart disease, with coronary artery disease (CAD) being the most common. In the setting of CAD, ventricular arrhythmias can result due to acute ischemia in the absence of preexisting myocardial scarring or in the presence of established scar from prior infarction without clinically significant ischemia. LV systolic dysfunction is an important predictor of risk for SCD in ischemic heart disease and in most nonischemic disorders, although other factors such as ventricular hypertrophy also play a role. Cardiac arrest and SCD can also occur due to primary electrical disorders in the absence of major structural abnormalities.

J Nucl Cardiol: 25 Jul 2016; epub ahead of print

A multifunctional CT technology: Reality or illusion for patient risk assessment?

Nakata T
A high-speed, multi-slice coronary computed tomography (CT) imaging has emerged as a promising or clinically available multifunctional technique for the assessment of myocardial ischemia, viability, ischemia-induced cardiac dysfunction, and coronary atherosclerotic alterations in patients with suspected or known coronary artery disease. Despite several technical issues remain to be resolved, cardiac CT imaging will have a reality as a multifunctional modality for guiding physicians in better decision-making for favorable clinical outcomes in patients with suspected coronary artery disease, provided that this imaging technology can contribute to characterization and localization of high-risk coronary atherosclerosis in combination with the quantitative evaluation of functional myocardial ischemia.

J Nucl Cardiol: 28 Mar 2016; epub ahead of print

Myocardial blood flow: Putting it into clinical perspective.

Schindler TH
In recent years, positron emission tomography/computed tomography (PET/CT)-determined myocardial perfusion in conjunction with myocardial blood flow (MBF) quantification in mL·g(-1)·min(-1) has emerged from mere research application to initial clinical use in the detection and characterization of the coronary artery disease (CAD) process. The concurrent evaluation of MBF during vasomotor stress and at rest with the resulting myocardial flow reserve (MFR = MBF during stress/MBF at rest) expands the scope of conventional myocardial perfusion imaging not only to the detection of the most advanced and culprit CAD, as evidenced by the stress-related regional myocardial perfusion defect, but also to the less severe or intermediate stenosis in patients with multivessel CAD. Due to the non-specific nature of the hyperemic MBF and MFR, the interpretation of hyperemic flow increases with PET/CT necessitates an appropriate placement in the context with microvascular function, wall motion analysis, and eventually underlying coronary morphology in CAD patients. This review aims to provide a comprehensive overview of various diagnostic scenarios of PET/CT-determined myocardial perfusion and flow quantification in the detection and characterization of clinically manifest CAD.

J Nucl Cardiol: 28 Dec 2015; epub ahead of print

Nuclear imaging for patients with a suspicion of infective endocarditis: Be part of the team!

Hyafil F, Rouzet F, Le Guludec D
The diagnosis of infective endocarditis (IE) is challenging and requires the association of morphological features suggestive of valvular infection such as the presence of vegetations or abscesses identified usually with echocardiography and positive blood culture or serologies suggestive of systemic bacterial infection. In the past 5 years, several groups confirmed the incremental value of FDG-PET imaging and radiolabeled leukocyte scintigraphy over echocardiography for the diagnosis of IE. Based on the latter studies, the presence of abnormal activity in the perivalvular region on either FDG-PET imaging or radiolabeled leukocyte scintigraphy has been added as a major criterion for the diagnosis of IE in the guidelines recently published. Nuclear physicians should therefore learn not only the imaging criteria in favor of active IE but also the pitfalls of these nuclear imaging techniques in order to give a useful answer to the referring physician for the management of these patients. In fact, the diagnosis of IE is often complex and requires the integration of multiple clinical, biological, and imaging parameters. Multi-disciplinary teams including cardiologists, infectious disease physicians, cardiac surgeons, and radiologists have been therefore set up in several institutions to discuss the diagnosis and management of patients with a suspicion of IE. It is now time for nuclear cardiologists to join the team.

J Nucl Cardiol: 29 Dec 2015; epub ahead of print

Transplant allograft vasculopathy: Role of multimodality imaging in surveillance and diagnosis.

Payne GA, Hage FG, Acharya D
Cardiac allograft vasculopathy (CAV) is a challenging long-term complication of cardiac transplantation and remains a leading long-term cause of graft failure, re-transplantation, and death. CAV is an inflammatory vasculopathy distinct from traditional atherosclerotic coronary artery disease. Historically, the surveillance and diagnosis of CAV has been dependent on serial invasive coronary angiography with intravascular imaging. Although commonly practiced, angiography is not without significant limitations. Technological advances have provided sophisticated imaging techniques for CAV assessment. It is now possible to assess the vascular lumen, vessel wall characteristics, absolute blood flow, perfusion reserve, myocardial contractile function, and myocardial metabolism and injury in a noninvasive, expeditious manner with little risk. The current article will review key imaging modalities for the surveillance, diagnosis, and prognosis of CAV and discuss coronary physiology of transplanted hearts with emphasis on the clinical implications for provocative and vasodilator stress testing.

J Nucl Cardiol: 28 Dec 2015; epub ahead of print

Reasons and implications of agreements and disagreements between coronary flow reserve, fractional flow reserve, and myocardial perfusion imaging.

Motwani M, Motlagh M, Gupta A, Berman DS, Slomka PJ
Information on coronary physiology and myocardial blood flow (MBF) in patients with suspected angina is increasingly important to inform treatment decisions. A number of different techniques including myocardial perfusion imaging (MPI), noninvasive estimation of MBF, and coronary flow reserve (CFR), as well as invasive methods for CFR and fractional flow reserve (FFR) are now readily available. However, despite their incorporation into contemporary guidelines, these techniques are still poorly understood and their interpretation to guide revascularization decisions is often inconsistent. In particular, these inconsistencies arise when there are discrepancies between the various techniques. The purpose of this article is therefore to review the basic principles, techniques, and clinical value of MPI, FFR, and CFR-with particular focus on interpreting their agreements and disagreements.

J Nucl Cardiol: 29 Dec 2015; epub ahead of print

SPECT blood pool phase analysis can accurately and reproducibly quantify mechanical dyssynchrony.

Lalonde M, Birnie D, Ruddy TD, Dekemp RA, Wassenaar RW
ObjectiveS: Phase analysis of SPECT blood pool imaging has the potential to assess mechanical dyssynchrony (MD). However, wall motion of the left ventricle (LV) from SPECT images can be based on either time-activity or time-distance curves. In this paper, these two techniques were compared using receiver-operator characteristics (ROC) analysis at detecting MD patients from a population of normal subjects. Methods: SPECT phase analysis was performed on 48 normal subjects (LVEF > 55%, normal wall motion, QRS < 120 ms), and 55 MD patients (LVEF < 35%, QRS > 120 ms). ROC analysis was individually performed on each of three phase parameters (phase standard deviation, synchrony, and entropy) for each LV wall motion technique. ROC area differences were assessed using the Student t-test. Intra- and inter-observer reproducibilities were investigated using regression analysis. Results: Time-activity-based phase analysis produced excellent ROC areas of .93 or better for all three phase parameters. The time-distance techniques produced significantly (P < .05) lower ROC areas in the range of .53-.76. Time-activity-based phase analysis had excellent intra- and inter-observer reproducibility with correlation coefficients >.96, compared to values of ~.85 for the time-distance methods. Conclusion: SPECT time-activity-based phase analysis had excellent sensitivity and specificity at detecting MD patients with very high intra- and inter-observer reproducibility.

J Nucl Cardiol: 29 Apr 2010; epub ahead of print

Nuclear imaging modalities for cardiac amyloidosis.

Bokhari S, Shahzad R, Castaño A, Maurer MS
Amyloidosis is a heterogeneous group of diseases characterized by localized or systemic deposition of insoluble extracellular fibrillary proteins in organs and tissues. Several types of amyloid can infiltrate the heart resulting in a restrictive cardiomyopathy, heart failure, and atrial and ventricular arrhythmias. Scintigraphy is a noninvasive method that may facilitate early diagnosis, distinguish various forms of cardiac amyloid, and may be useful in following disease burden. The amyloid-specific tracers presented in this article have been used with planar imaging and/or single-photon emission computed tomography. To date, there are no approved cardiac amyloid tracers although investigational tracers are currently under examination. This article serves to review the current nuclear imaging modalities available in the detection of cardiac amyloid.

J Nucl Cardiol: 27 Oct 2013; epub ahead of print

Diagnosing coronary artery disease with hybrid PET/CT: It takes two to tango.

Danad I, Raijmakers PG, Knaapen P
The noninvasive diagnosis of coronary artery disease (CAD) is a challenging task. Although a large armamentarium of imaging modalities is available to evaluate the functional consequences of the extent and severity of CAD, cardiac perfusion positron emission tomography (PET) is considered the gold standard for this purpose. Alternatively, noninvasive anatomical imaging of coronary atherosclerosis with coronary computed tomography angiography (CCTA) has recently been successfully implemented in clinical practice. Although each of these diagnostic approaches has its own merits and caveats, functional and morphological imaging techniques provide fundamentally different insights into the disease process and should be considered to be complementary rather than overlapping. Hybrid imaging with PET/CT offers the possibility to evaluate both aspects nearly simultaneously, and studies have demonstrated that such a comprehensive assessment results in superior diagnostic accuracy, better prognostication, and helps in guiding clinical patient management. The aim of this review is to discuss the value of stand-alone CCTA and PET in CAD, and to summarize the available data on the surplus value of hybrid PET/CT including its strengths and limitations.

J Nucl Cardiol: 10 Jul 2013; epub ahead of print

The role of myocardial perfusion imaging in evaluating patients with myocardial bridging.

Tang K, Wang L, Shi R, Zheng X, ... Zhao X, Lu R
Background: Myocardial bridging (MB) is a common, congenital coronary-abnormality that is found on average in one out of every three adults at autopsy (Moehlenkamp et al in Circulation, 106:2616-2622, 2002; Erbel et al in Circulation, 120:357-359, 2009). However, its clinical significance and impact on myocardial ischemia remains controversial and unclear. Myocardial perfusion imaging (MPI) is widely used to assess myocardial ischemia in patients with known or suspected coronary artery disease, and is frequently performed to evaluate the hemodynamic significance of MB. This study was undertaken to determine the use of MPI in evaluating MB and to identify the characteristics of MB associated with perfusion defects using MPI. Methods and results: Thirty-nine patients with MB of the left anterior descending (LAD) artery as documented by coronary angiography (CA) were enrolled for this study. None of the patients exhibited other forms of heart disease as determined by both CA and stress-rest MPI, no later than 1 month prior to the study. Using MPI, eight patients (20.5%) were found to have perfusion defects in the corresponding myocardial areas. This frequency was significantly higher when compared with results obtained by stress electrocardiogram. The difference in the mean systolic narrowing of bridging segments was statistically significant between patients with and without ischemia. The positive rate of reversible defects in patients with severe systolic narrowing was significantly higher than in patients with mild-to-moderate systolic narrowing. However, there was no significant difference either between the mean length of the tunneled artery in patients with and without abnormal MPI or the positive rate of abnormal MPI in patients with different locations of the tunneled artery. Conclusions: MPI is an effective, noninvasive technique for the evaluation of patients with MB. The myocardial ischemia that resulted from bridging is associated more closely with the degree of systolic narrowing than with the length of tunneled artery or the location of MB.

J Nucl Cardiol: 11 Nov 2010; epub ahead of print

Myocardial perfusion GSPECT imaging in patients with myocardial bridging.

Gawor R, Kuśmierek J, Płachcińska A, Bieńkiewicz M, ... Piotrowski G, Chiżyński K
Background: The aim of this study was to investigate the incidence, reversibility, and severity of LV perfusion abnormalities in patients with isolated myocardial bridges using a gated myocardial perfusion SPECT study (GSPECT). Methods: A retrospective study involved 42 patients without history of myocardial infarction, with isolated myocardial bridges detected in coronary angiography and no substantial evidence of atherosclerotic changes in coronary arteries. In all patients a gated SPECT study was performed at both rest and stress, after intravenous administration of (99m)Tc MIBI. Reconstructed slices were analyzed using a 20-segment model of the left ventricle. Results: Incidence and severity of stress-induced ischemia were related to degree of artery constriction (P = .002 and .00014, respectively). Perfusion abnormalities were detected only in patients with critical narrowing (≥50%) of artery (in 12 out of 28, i.e., 43% of patients). Summed stress scores (SSS) ranged from 4 to 11 (mean 7), indicating slight or moderate defect intensity. Only 1 patient presented with a SSS value of 31 (severe defect). Perfusion defects were stress induced in 70 out of 72 (97%) segments with abnormal perfusion. Conclusion: Perfusion abnormalities were observed in ab. 40% of patients with critical (≥50%) narrowing of artery affected by bridging and were mild, stress induced.

J Nucl Cardiol: 08 Aug 2011; epub ahead of print

Left main coronary artery disease: A review of the spectrum of noninvasive diagnostic modalities.

Sareen N, Ananthasubramaniam K
Medically managed significant left main (LM) stem disease has been considered a determinant of increased cardiac mortality approaching 50% at 3-year follow-up. Despite the clinical significance of LM disease, studies comparing the various diagnostic modalities, especially noninvasive, are sparse. Clinicians, particularly imagers, should be aware of the strengths and weaknesses of existing modalities to diagnose LM disease as integrating many clues (history, symptoms, electrocardiogram, and stress hemodynamics are essential to suspect this diagnosis and proceed to the next step). Here we review the existing data on the current role of electrocardiography, nuclear myocardial perfusion imaging (single photon emission computed tomography and positron emission tomography), stress echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging in diagnostic evaluation of LM disease. Wherever applicable we have extended our discussion to multivessel coronary artery disease encompassing scenarios where LMS can present as LM equivalent with or without extensive multivessel coronary artery disease.

J Nucl Cardiol: 20 Oct 2015; epub ahead of print

Recent advances in metabolic imaging.

Gropler RJ
Abnormalities in myocardial substrate metabolism play a central role in the manifestations of most forms of cardiac disease such as ischemic heart disease, heart failure, hypertensive heart disease, and the cardiomyopathy due to either obesity or diabetes mellitus. Their importance is exemplified by both the development of numerous imaging tools designed to detect the specific metabolic perturbations or signatures related to these different diseases, and the vigorous efforts in drug discovery/development targeting various aspects of myocardial metabolism. Since the prior review in 2005, we have gained new insights into how perturbations in myocardial metabolism contribute to various forms of cardiac disease. For example, the application of advanced molecular biologic techniques and the development of elegant genetic models have highlighted the pleiotropic actions of cellular metabolism on energy transfer, signal transduction, cardiac growth, gene expression, and viability. In parallel, there have been significant advances in instrumentation, radiopharmaceutical design, and small animal imaging, which now permit a near completion of the translational pathway linking in-vitro measurements of metabolism with the human condition. In this review, most of the key advances in metabolic imaging will be described, their contribution to cardiovascular research highlighted, and potential new clinical applications proposed.

J Nucl Cardiol: 30 Oct 2013; epub ahead of print

Clinical topic: Nuclear imaging in hypertrophic cardiomyopathy.

Delgado V, Bax JJ
Non-invasive cardiac imaging plays a central role in the diagnosis and management of patients with hypertrophic cardiomyopathy. Transthoracic echocardiography is the imaging technique of first choice to evaluate wall thickness, left ventricular systolic and diastolic function, presence of left ventricular outflow tract obstruction, and abnormal mitral anatomy, whereas cardiac magnetic resonance provides additional information on tissue characterization (replacement fibrosis) using late gadolinium enhancement. Nuclear imaging techniques permit also the assessment of left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy but are more frequently used to evaluate myocardial ischemia (particularly assessment of microvascular dysfunction using positron emission tomography) and abnormal sympathetic myocardial innervation. This review article provides an overview of the use of nuclear imaging techniques to refine the phenotyping and risk stratification of patients with hypertrophic cardiomyopathy with particular focus on prediction of progression to overt heart failure, detection of myocardial ischemia, and evaluation of the arrhythmogenic substrate and risk of sudden cardiac death.

J Nucl Cardiol: 29 Dec 2014; epub ahead of print

Pitfalls and artifacts using the D-SPECT dedicated cardiac camera.

Allie R, Hutton BF, Prvulovich E, Bomanji J, Michopoulou S, Ben-Haim S
Myocardial perfusion imaging is a well-established and widely used imaging technique for the assessment of patients with known or suspected coronary artery disease. Pitfalls and artifacts associated with conventional gamma cameras are well known, and the ways to avoid and correct them have been described. In recent years solid-state detector dedicated cardiac cameras were introduced and have been shown to offer improved accuracy in addition to new imaging protocols and novel applications. The purpose of this manuscript is to familiarize the readers with the causes and effects of technical, patient-related, and operator-related pitfalls and artifacts associated with the D-SPECT dedicated cardiac camera with solid-state detectors. The manuscript offers guidance on how to avoid these factors, how to detect them, and how to correct better for them, providing high-quality diagnostic images.

J Nucl Cardiol: 24 Sep 2015; epub ahead of print

Molecular imaging to predict ventricular arrhythmia in heart failure.

Wollenweber T, Bengel FM
Ventricular tachycardia (VT) is a major cause of sudden cardiac death (SCD) in patients with heart failure (HF). Left ventricular ejection fraction (LVEF) and heart failure class according to the New York Heart association (NYHA) are in most common use to identify patients that may benefit from implantable cardioverter defibrillator (ICD) therapy. But during 3 years of follow up only 35% of patients receive appropriate ICD action. Therefore, there is a continued need for refinement of selection criteria for ICD implantation. In this regard, molecular imaging of the autonomic nervous system, which plays a central role in HF progression and cardiac electro-mechanical regulation, can make a substantial contribution. This article reviews the currently available literature concerning the value of molecular neuronal cardiac imaging for prediction of ventricular arrhythmias in HF patients.

J Nucl Cardiol: 19 Aug 2014; epub ahead of print

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.

Ronan G
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.

J Nucl Cardiol: 29 Dec 2013; epub ahead of print

Noninvasive monitoring the biology of atherosclerotic plaque development with radiolabeled annexin V and matrix metalloproteinase inhibitor in spontaneous atherosclerotic mice.

Tekabe Y, Li Q, Luma J, Weisenberger D, ... Narula J, Johnson LL
ObjectiveS: To compare the ability of (99m)Tc-labeled broad-based matrix metalloproteinase inhibitor (RP805) (MPI) and (99m)Tc-annexin V to identify more advanced atherosclerotic disease in apolipoprotein E-null (apoE(-/-)) mice. Background: Both MMP expression and apoptotic cell death occur in both early and in advanced atherosclerotic plaques. Methods: Eight 6-9-week-old apoE(-/-) mice, 10 apoE(-/-) mice at 20 weeks, and 12 apoE(-/-) at 40 weeks were injected with both tracers in alternating sequence separated by 48 h, underwent planar imaging and were killed. Radiotracer uptake was quantified from the scans as percent whole body and from tissue as percent injected dose per gram (%ID/g). Quantitative immunohistopathology of the aorta and carotids for macrophages, MMPs, and caspase was performed. Results: At 6 weeks, mice showed no tracer uptake in the chest or neck and had minimal lesion. At 20 weeks, uptake of annexin V as %ID was borderline higher than MPI (1.10 +/- .48% vs .77 +/- .31%, P = .09), between 20 and 40 weeks aortic lesion area increased from 37.4 +/- 12.0% to 46.2 +/- 7.4% and at 40 weeks MPI was significantly greater than annexin V uptake (1.11 +/- .66% vs .70 +/- .16%, P = .05). On histology there were greater increases in % MMP-2 and -9 than % caspase positive cells. Carotid uptake of MPI was greater than annexin V at both 20 and 40 weeks (1.25 +/- .48% vs .78 +/- .25%, P = .02 and 3.70 +/- 1.45% vs 2.25 +/- .66%, P = .005). The carotid lesion area at 40 weeks was 74 +/- 9% with greater % cells positive for MMP\'s than caspase. %ID/g annexin V correlated significantly with % macrophages and with caspase-3 positive cells and %ID/g MPI correlated significantly with % macrophages and with MMP-2 and -9 positive cells. Conclusions: In apoE(-/-) mice, MMP expression is greater than apoptosis as the disease progresses and MPI may be a better imaging agent for more advanced disease.

J Nucl Cardiol: 11 Aug 2010; epub ahead of print

Comparison of the atherosclerotic burden among asymptomatic patients vs matched volunteers.

Rozanski A, Gransar H, Shaw L, Wong ND, ... Friedman JD, Berman DS
Background: While asymptomatic patients should have a lower risk of cardiac events compared to symptomatic patients referred for cardiac stress testing, comparable event rates have been noted in some prior prognostic studies. To test if a high burden of undetected atherosclerosis among asymptomatic patients helps explain such findings, we compared atherosclerotic burden, as measured by coronary artery calcium (CAC) scanning, in propensity-matched groups of volunteers and asymptomatic patients. Methods: CAC scans were performed on a research basis in 136 asymptomatic patients referred for exercise myocardial perfusion SPECT and in 1,398 volunteers. We performed matching by propensity scores to compare volunteers with the same CAD risk factor profile as our asymptomatic patients. Results: Among our matched groups, asymptomatic patients had significantly greater mean CAC scores than volunteers (394 ± 805 vs 151 ± 349, P = .001), primarily due to a higher frequency of CAC scores >1,000 (15.4% vs 2.5%, P < .001). Inducible myocardial ischemia by SPECT was present in 7% of patients, but was selectively concentrated among those with CAC scores >1,000, occurring in 27.0% of such patients vs only 1.9% among patients with CAC scores <1,000 (P < .0001). Conclusions: In contrast to asymptomatic volunteers, asymptomatic patients referred for cardiac stress testing possess more extensive atherosclerosis as measured by CAC. Among asymptomatic patients with high CAC scores, the frequency of concomitant inducible myocardial ischemia is high. These results help explain prior prognostic studies concerning asymptomatic patients and indicate the importance of making a clinical distinction between healthy subjects and asymptomatic patients with respect to atherosclerotic risk.

J Nucl Cardiol: 24 Dec 2010; epub ahead of print

Quantity of viable myocardium required to improve survival with revascularization in patients with ischemic cardiomyopathy: A meta-analysis.

Inaba Y, Chen JA, Bergmann SR
Background: This meta-analysis was conducted to determine optimal cutoff values for the assessment of viability using various imaging techniques for which revascularization would offer a survival benefit in patients with ischemic cardiomyopathy (ICM). Methods and results: We searched five electronic databases to identify relevant studies through December 2008. Relative risks of cardiac death, both in patients with and without viability, were calculated in each study. In order to estimate the optimal threshold for the presence of viability, we assumed a linear relationship between the amount of viable myocardium and survival benefit of revascularization. Twenty-nine studies (4,167 patients) met the inclusion criteria. The optimal threshold for the presence of viability was estimated to be 25.8% (95% CI: 16.6-35.0%) by positron emission tomography using 18F-fluorodeoxyglucose-perfusion mismatch, 35.9% (95% CI: 31.6-40.3%) by stress echocardiography using contractile reserve or ischemic responses, and 38.7% (95% CI: 27.7-49.7%) by single photon emission computed tomography using thallium-201 or technetium-99m MIBI myocardial perfusion. Conclusions: The calculated amount of viable myocardium determined to lead to improved survival was different among imaging techniques. Thus, separate cutoff values for imaging modalities may be helpful in determining which patients with ICM benefit from revascularization.

J Nucl Cardiol: 09 Apr 2010; epub ahead of print

Prompt-gamma compensation in Rb-82 myocardial perfusion 3D PET/CT.

Esteves FP, Nye JA, Khan A, Folks RD, ... Raggi P, Votaw JR
Objective: To compare the diagnostic accuracy of Rb-82 myocardial perfusion three-dimensional (3D) PET with and without prompt-gamma compensation (PGC). Methods and results: Retrospective, single center study of 76 patients who had rest and adenosine stress Rb-82 myocardial perfusion 3D PET. All studies were acquired using a Siemens Biograph-40 PET/CT scanner and were reconstructed with and without PGC. Fifty-seven patients (mean age 63 +/- 11 years, 26 men) had coronary angiography within 40 days of Rb-82 imaging. Nineteen patients (mean age 43 +/- 7 years, 10 men) had low likelihood of coronary artery disease (CAD). All PET images were scored by consensus of two blinded readers on a standard 5-point scale using a 17-segment left ventricular model. A normal PET test was defined as a summed stress score of less than four. Obstructive CAD at coronary angiography was used as the gold-standard and was defined as luminal stenoses >/=50% in one or more major coronary arteries. The prevalence of obstructive disease at coronary angiography was 68% (39/57). The mean summed stress score was 12 +/- 12 for PGC images and was 18 +/- 14 for non-PGC images. Sensitivity and specificity for obstructive CAD were 90% (95% CI 88-99) and 72% (95% CI 52-93) for PGC images and 95% (95% CI 88-100) and 22% (95% CI 3-41) for non-PGC images. Conclusion: PGC in Rb-82 3D PET improves the specificity for obstructive CAD at coronary angiography with no significant loss in sensitivity.

J Nucl Cardiol: 25 Nov 2009; epub ahead of print

Intra- and inter-operator repeatability of myocardial blood flow and myocardial flow reserve measurements using rubidium-82 pet and a highly automated analysis program.

Klein R, Renaud JM, Ziadi MC, Thorn SL, ... Beanlands RS, Dekemp RA
Background: Changes in myocardial blood flow between rest and stress states are commonly used to diagnose coronary artery disease. Relative myocardial perfusion imaging (MPI) is used routinely while myocardial blood flow quantification (MBF) may improve the sensitivity for detection of early disease. The ratio of flow at stress and rest (S/R) and their difference (S-R) have both been proposed as a means to detect regions with reduced myocardial flow reserve (MFR). In this study, we describe a highly automated method to calculate regional and global rest, stress, S/R, and S-R polar maps of the left ventricle myocardium. Methods: We measured the inter- and intra-operator variability using two randomized datasets (n = 30 each) for each of two operators (novice and expert) with correlation and Bland-Altman reproducibility coefficient (RPC%) analyses. Results: S-R MBF had less inter-operator dependent variability than S/R (RPC% = 5.0% vs 12.6%, P < .001). While there was no difference in intra-operator variability with S-R MBF (novice vs expert RPC% = 6.4% vs 5.9%, P = ns), variability was higher in the novice-operator for S/R (RPC% = 16.8% vs 8.5% respectively, P < .001), suggesting that S-R may be preferred for detecting small changes in MFR. The novice operator\'s intervention pattern became more similar to that of the expert in the later dataset, emphasizing the need for adequate training and quality assurance. Conclusion: The proposed method results in low operator-dependent variability, suitable for routine use.

J Nucl Cardiol: 13 Apr 2010; epub ahead of print

Comparison of Framingham, PROCAM, SCORE, and Diamond Forrester to predict coronary atherosclerosis and cardiovascular events.

Versteylen MO, Joosen IA, Shaw LJ, Narula J, Hofstra L
Background: Cardiologists are often confronted with patients presenting with chest pain, in whom clinical risk profiling is required. We studied four frequently used risk scores in their ability to predict for coronary artery disease (CAD) and major adverse cardiovascular events in patients presenting with stable chest pain at the cardiology outpatient clinic. Methods and results: We enrolled 1,296 stable chest pain patients, who underwent cardiac computed tomographic angiography (CCTA) to assess CAD (any, significant: stenosis ≥50%). Framingham (FRS), PROCAM, SCORE risk score, and Diamond Forrester pre-test probability were calculated. All patients were followed up for a mean 19 ± 9 months for all cardiovascular events (mortality, acute coronary syndrome, revascularization >90 days after CCTA). In ROC-analysis for prediction of significant CAD, the areas under the curve for FRS; 0.68 (95% confidence interval: 0.64-0.72) and for SCORE; 0.69 (95% confidence interval: 0.65-0.72) were significantly higher than for PROCAM; 0.64 (95% confidence interval: 0.61-0.68; P ≤ .001), as well as marginally higher than for Diamond Forrester; 0.65 (95% confidence interval: 0.61-0.68; P ≤ .05). Low FRS category showed the lowest number of patients with significant CAD, compared to patients with low risk using PROCAM, SCORE or Diamond Forrester (P < .001). Also, low FRS category showed less events (compared to PROCAM and SCORE; P < .001, for Diamond Forrester; P = .14). Conclusion: Our data show that in a stable chest pain population, the ability of FRS and SCORE to predict for CAD was similar and better compared to PROCAM and Diamond Forrester. The number of low risk patients showing significant CAD or events was lower using FRS. Consequently, risk categorization using FRS seems to be safest to stratify stable chest pain patients prior to CCTA.

J Nucl Cardiol: 19 Jul 2011; epub ahead of print

Taking the perfect nuclear image: Quality control, acquisition, and processing techniques for cardiac SPECT, PET, and hybrid imaging.

Case JA, Bateman TM
Nuclear Cardiology for the past 40 years has distinguished itself in its ability to non-invasively assess regional myocardial blood flow and identify obstructive coronary disease. This has led to advances in managing the diagnosis, risk stratification, and prognostic assessment of cardiac patients. These advances have all been predicated on the collection of high quality nuclear image data. National and international professional societies have established guidelines for nuclear laboratories to maintain high quality nuclear cardiology services. In addition, laboratory accreditation has further advanced the goal of the establishing high quality standards for the provision of nuclear cardiology services. This article summarizes the principles of nuclear cardiology single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging and techniques for maintaining quality: from the calibration of imaging equipment to post processing techniques. It also will explore the quality considerations of newer technologies such as cadmium zinc telleride (CZT)-based SPECT systems and absolute blood flow measurement techniques using PET.

J Nucl Cardiol: 21 Jul 2013; epub ahead of print

Radionuclide imaging of cardiac autonomic innervation.

Ji SY, Travin MI
Cardiac autonomic function plays a crucial role in health and disease, with abnormalities both reflecting the severity of the disease and contributing specifically to clinical deterioration and poor prognosis. Radiotracer analogs of the sympathetic mediator norepinephrine have been investigated extensively, and are at the brink of potential widespread clinical use. The most widely studied SPECT tracer, I-123 metaiodobenzylguanidine ((123)I-mIBG) has consistently shown a strong, independent ability to risk stratify patients with advanced congestive heart failure. Increased global cardiac uptake appears to have a high negative predictive value in terms of cardiac events, especially death and arrhythmias, and therefore and may have a role in guiding therapy, particularly by helping to better select patients unresponsive to conventional medical therapies who would benefit from device therapies such as an ICD (implantable cardioverter defibrillator), CRT (cardiac resynchronization therapy), LVAD (left ventricular assist device), or cardiac transplantation. Cardiac autonomic imaging with SPECT and PET tracers also shows potential to assess patients following cardiac transplant, those with primary arrhythmic condition, coronary artery disease, diabetes mellitus, and during cardiotoxic chemotherapy. Radiotracer imaging of cardiac autonomic function allows visualization and quantitative measurements of underlying molecular aspects of cardiac disease, and should therefore provide a perspective that other cardiac tests cannot.

J Nucl Cardiol: 10 May 2010; epub ahead of print

Myocardial perfusion imaging analysis in patients with regurgitant valvular heart disease.

Sidhu M, Chan AK, Chockalingam A, Dresser T
Background/AIM: We noticed that there was decreased correlation of the findings from myocardial perfusion imaging (MPI) and cardiac catheterization (CATH) in patients with mitral regurgitation (MR) and aortic regurgitation (AR) compared to patients without valve disease. Methods: Through a systematic review of MPI records at the Harry S. Truman Memorial Veterans\' Hospital between 1998 and 2008, we identified 58 patients with at least moderate MR or AR by echocardiogram who underwent cardiac catheterization within 6 months of the MPI study. A control group was formulated with 60 patients who did not have significant MR or AR on echocardiogram and who had both MPI and CATH. Correlation between MPI and CATH was graded as complete, partial, or absent. Results: Correlation between MPI and CATH was lower in the valve disease patients (study group) when compared to controls. Correlation was complete in 76% of study patients and 90% of controls, partial in 15% of study patients and 5% of controls, and absent in 9% of study patients and 5% of controls. Differences between the groups were significant (P < .05). Conclusions: Patients with regurgitant valvular heart disease may have myocardial perfusion abnormalities that are not associated with angiographic critical coronary stenosis.

J Nucl Cardiol: 08 Feb 2011; epub ahead of print

Gated SPECT in assessment of regional and global left ventricular function: An update.

Abidov A, Germano G, Hachamovitch R, Slomka P, Berman DS
Gated myocardial perfusion SPECT (GSPECT) is a major clinical tool, widely used for performing myocardial perfusion imaging procedures. In this review, we have presented the fundamentals of GSPECT and the ways in which the functional measurements it provides have contributed to the emergence of myocardial perfusion SPECT in its important role as a major tool of modern cardiac imaging. GSPECT imaging has shown unique capability to provide accurate, reproducible and operator-independent quantitative data regarding myocardial perfusion, global and regional systolic and diastolic function, stress-induced regional wall-motion abnormalities, ancillary markers of severe and extensive disease, left ventricular geometry and mass, as well as the presence and extent of myocardial scar and viability. Adding functional data to perfusion provides an effective means of increasing both diagnostic accuracy and reader\'s confidence in the interpretation of the results of perfusion scans. Assessment of global and regional LV function has improved the prognostic power of myocardial perfusion SPECT and has been shown in a large registry to add to the perfusion assessment in predicting benefit from revascularization.

J Nucl Cardiol: 14 Nov 2013; epub ahead of print

Motion frozen (18)F-FDG cardiac PET.

Le Meunier L, Slomka PJ, Dey D, Ramesh A, ... Germano G, Berman DS
Background: PET reconstruction incorporating spatially variant 3D Point Spread Function (PSF) improves contrast and image resolution. "Cardiac Motion Frozen" (CMF) processing eliminates the influence of cardiac motion in static summed images. We have evaluated the combined use of CMF- and PSF-based reconstruction for high-resolution cardiac PET. Methods: Static and 16-bin ECG-gated images of 20 patients referred for (18)F-FDG myocardial viability scans were obtained on a Siemens Biograph-64. CMF was applied to the gated images reconstructed with PSF. Myocardium to blood contrast, maximum left ventricle (LV) counts to defect contrast, contrast-to-noise (CNR) and wall thickness with standard reconstruction (2D-AWOSEM), PSF, ED-gated PSF, and CMF-PSF were compared. Results: The measured wall thickness was 18.9 ± 5.2 mm for 2D-AWOSEM, 16.6 ± 4.5 mm for PSF, and 13.8 ± 3.9 mm for CMF-PSF reconstructed images (all P < .05). The CMF-PSF myocardium to blood and maximum LV counts to defect contrasts (5.7 ± 2.7, 10.0 ± 5.7) were higher than for 2D-AWOSEM (3.5 ± 1.4, 6.5 ± 3.1) and for PSF (3.9 ± 1.7, 7.7 ± 3.7) (CMF vs all other, P < .05). The CNR for CMF-PSF (26.3 ± 17.5) was comparable to PSF (29.1 ± 18.3), but higher than for ED-gated dataset (13.7 ± 8.8, P < .05). Conclusion: Combined CMF-PSF reconstruction increased myocardium to blood contrast, maximum LV counts to defect contrast and maintained equivalent noise when compared to static summed 2D-AWOSEM and PSF reconstruction.

J Nucl Cardiol: 16 Dec 2010; epub ahead of print

Randomized transcoronary delivery of CD34(+) cells with perfusion versus stop-flow method in patients with recent myocardial infarction: Early cardiac retention of (99m)Tc-labeled cells activity.

Musialek P, Tekieli L, Kostkiewicz M, Majka M, ... Zmudka K, Tracz W
Background: For transcoronary progenitor cells\' administration, injections under flow arrest (over-the-wire balloon technique, OTW) are used universally despite lack of evidence for being required for cell delivery or being effective in stimulating myocardial engraftment. Flow-mediated endothelial rolling is mandatory for subsequent cell adhesion and extravasation. Methods: To optimize cell directing toward the coronary endothelium under maintained flow, the authors developed a cell-delivery side-holed perfusion catheter (PC). Thirty-four patients (36-69 years, 30 men) with primary stent-assisted angioplasty-treated anterior MI (peak TnI 151 [53-356]ng/dL, mean[range]) were randomly assigned to OTW or PC autologous (99)Tc-extametazime-labeled bone marrow CD34(+) cells (4.34 [0.92-7.54] × 10(6)) administration at 6-14 days after pPCI (LVEF 37.1 [24-44]%). Myocardial perfusion ((99m)Tc-MIBI) and labeled cells\' activity were evaluated (SPECT) at, respectively, 36-48 h prior to and 60 min after delivery. Results: In contrast to OTW coronary occlusions, no intolerance or ventricular arrhythmia occurred with PC cells\' administration (P < .001). One hour after delivery, 4.86 [1.7-7.6]% and 5.05 [2.2-9.9]% activity was detected in the myocardium (OTW and PC, respectively, P = .84). Labeled cell activity was clearly limited to the (viable) peri-infarct zone in 88% patients, indicating that the infarct core zone may be largely inaccessible to transcoronary-administered cells. Conclusions: Irrespective of the transcoronary delivery method, only ≈5% of native (i.e., non-engineered) CD34(+) cells spontaneously home to the injured myocardium, and cell retention occurs preferentially in the viable peri-infarct zone. Although the efficacy of cell delivery is not increased with the perfusion method, by avoiding provoking ischemic episodes PC offers a rational alternative to the OTW delivery.

J Nucl Cardiol: 16 Dec 2010; epub ahead of print

The role of nuclear imaging in pulmonary hypertension.

Ohira H, Beanlands RS, Davies RA, Mielniczuk L
Pulmonary hypertension (PH) is a disease characterized by a chronic elevation of pulmonary artery pressure from various causes. Pulmonary artery hypertension (PAH) is one of subtype which results in premature death often as a result of right ventricular (RV) dysfunction. In spite of the recent progress in novel cardiac imaging techniques and new drugs for PAH, there remain significant unresolved issues including a need for earlier diagnosis, refinement of risk stratification, and monitoring the effects of treatment. Cardiac and pulmonary imaging with transthoracic echocardiography (TTE) with Doppler, magnetic resonance imaging (MRI), and computed tomography (CT) are done routinely in many clinical centers. However, routine and emerging nuclear techniques may have a pivotal role of assessment of the patient with PH, and is currently the subject of significant research. Potential Roles for Nuclear Imaging in the Evaluation of the PH Patient: (1) Evaluation of cardiac structure and function (RNA) (non-nuclear techniques would include TTE, CT, and MRI). (2) Functional imaging. This includes the use of ventilation-perfusion scintigraphy (V/Q scan) to diagnose chronic thromboembolic pulmonary hypertension (CTEPH), 123l-metaiodobenzylguanidine (MIBG) imaging to evaluate the cardiac sympathetic nervous system (non-nuclear techniques include invasive right heart catheterization and TTE). (3) Measurement of RV perfusion (with gated SPECT studies). (4) Evaluation of cardiac and pulmonary metabolism (PET scans). This review article will summarize the pathophysiology, classification, natural history, and diagnostic approach of PH. Current and emerging nuclear techniques will be discussed under the four themes of evaluation of structure, functional imaging, flow, and metabolism. These will be compared to current and emerging nuclear and non-nuclear diagnostic tests in the evaluation and management of patients with PH. We will also discuss research applications exploring new insights into flow and metabolism in the right heart and lung and the application of new radioligands.

J Nucl Cardiol: 26 Aug 2014; epub ahead of print

Quantitative myocardial perfusion imaging by cardiovascular magnetic resonance and positron emission tomography.

Bratis K, Mahmoud I, Chiribiri A, Nagel E
Recent studies have demonstrated that a detailed knowledge of the extent of angiographic coronary artery disease (CAD) is not a prerequisite for clinical decision making, and the clinical management of patients with CAD is more and more focused towards the identification of myocardial ischemia and the quantification of ischemic burden. In this view, non-invasive assessment of ischemia and in particular stress imaging techniques are emerging as preferred and non-invasive options. A quantitative assessment of regional myocardial perfusion can provide an objective estimate of the severity of myocardial injury and may help clinicians to discriminate regions of the heart that are at increased risk for myocardial infarction. Positron emission tomography (PET) has established itself as the reference standard for myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) quantification. Cardiac magnetic resonance (CMR) is increasingly used to measure MBF and MPR by means of first-pass signals, with a well-defined diagnostic performance and prognostic value. The aim of this article is to review the currently available evidence on the use of both PET and CMR for quantification of MPR, with particular attention to the studies that directly compared these two diagnostic methods.

J Nucl Cardiol: 21 Jul 2013; epub ahead of print

Molecular imaging in cardiovascular disease: Which methods, which diseases?

Lindner JR, Sinusas A
Techniques for in vivo assessment of disease-related molecular changes are being developed for all forms of non-invasive cardiovascular imaging. The ability to evaluate tissue molecular or cellular phenotype in patients has the potential to not only improve diagnostic capabilities but to enhance clinical care either by detecting disease at an earlier stage when it is more amenable to therapy, or by guiding most appropriate therapies. These new techniques also can be used in research programs in order to characterize pathophysiology and as a surrogate endpoint for therapeutic efficacy. The most common approach for molecular imaging involves the creation of novel-targeted contrast agents that are designed so that their kinetic properties are different in disease tissues. The main focus of this review is not to describe all the different molecular imaging approaches that have been developed, but rather to describe the status of the field and highlight some of the clinical and research applications that molecular imaging will likely provide meaningful benefit. Specific target areas include assessment of atherosclerotic disease, tissue ischemia, and ventricular and vascular remodeling.

J Nucl Cardiol: 03 Oct 2013; epub ahead of print

The role of pharmacological stress testing in women.

Standbridge K, Reyes E
Pharmacological stress is an alternative method to dynamic exercise that combined with noninvasive imaging allows the detection of flow-limiting coronary artery disease (CAD). It represents the stress procedure of choice in patients who cannot exercise appropriately. In women, pharmacological stress combined with myocardial perfusion scintigraphy (MPS) has demonstrated to be highly accurate for the detection of obstructive CAD and a valuable tool that helps separate patients at low cardiac risk from those with an adverse prognosis. Pharmacological stress with positron emission tomographic (PET) imaging is increasingly used in the investigation of suspected obstructive CAD; available evidence shows that the diagnostic profile and prognostic value of stress PET imaging is similar to that of stress MPS in women.

J Nucl Cardiol: 11 Aug 2016; epub ahead of print

Left ventricular dyssynchrony assessment by phase analysis from gated PET-FDG scans.

Pazhenkottil AP, Buechel RR, Nkoulou R, Ghadri JR, ... Gaemperli O, Kaufmann PA
Background: The outcome of patients with severe ischaemic left ventricular (LV) dysfunction is determined by the extent of myocardial viability and the presence of LV dyssynchrony. We aimed at assessing both parameters from the same imaging method, i.e. gated positron emission tomography (PET) F18-fluorodeoxyglucose (FDG) scans. Methods: Phase analysis from Emory Cardiac Toolbox was applied on gated PET-FDG scans to assess histogram bandwidth and standard deviation (SD) as a measure of LV dyssynchrony in 30 heart failure patients (mean ejection fraction: 30.2% ± 13.8%) referred for the evaluation of myocardial viability. Cut-off values from single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) best predicting cardiac resynchronization therapy (CRT) response served as standard of reference (bandwidth < 135°; phase SD < 43°). Severe LV dyssynchrony was diagnosed if both SPECT-MPI values were above these limits. Intraclass correlation and clinical agreement in detection of severe LV dyssynchrony by PET vs SPECT were assessed. Results: There was a significant correlation between PET-FDG and SPECT-MPI for bandwidth (r = 0.88, P < .001) and phase SD (r = 0.88, P < .001) resulting in an excellent clinical agreement between the two methods of 93%. Conclusions: Accurate LV dyssynchrony assessment by phase analysis of gated PET-FDG scans is feasible, allowing assessing myocardial viability and severe LV dyssynchrony in one scan.

J Nucl Cardiol: 14 Jun 2011; epub ahead of print

Clinical decision support systems in myocardial perfusion imaging.

Garcia EV, Klein JL, Taylor AT
Diagnostic imaging is becoming more complicated, physicians are also required to master an ever-expanding knowledge base and take into account an ever increasing amount of patient-specific clinical information while the time available to master this knowledge base, assemble the relevant clinical data, and apply it to specific tasks is steadily shrinking. Compounding these problems, there is an ever increasing number of aging "Baby Boomers" who are becoming patients coupled with a declining number of cardiac diagnosticians experienced in interpreting these studies. Hence, it is crucial that decision support tools be developed and implemented to assist physicians in interpreting studies at a faster rate and at the highest level of up-to-date expertise. Such tools will minimize subjectivity and intra- and inter-observer variation in image interpretation, help achieve a standardized high level of performance, and reduce healthcare costs. Presently, there are many decision support systems and approaches being developed and implemented to provide greater automation and to further objectify and standardize analysis, display, integration, interpretation, and reporting of myocardial perfusion SPECT and PET studies. This review focuses on these systems and approaches.

J Nucl Cardiol: 30 Jan 2014; epub ahead of print

The role of radionuclide imaging in heart failure.

Gulati V, Ching G, Heller GV
The incidence of heart failure (HF) is increasing and it remains the only area in cardiovascular disease wherein hospitalization rates and mortalities have worsened in the past 25 years. This review is provided to assess the role of radionuclide imaging in HF. The focus is on three aspects: the value of nuclear imaging to distinguish ischemic from non-ischemic etiologies; risk stratification of patients with HF with evaluation of candidates for specific treatment strategies; and the role of cardiac neuronal imaging in patients with HF. Distinguishing ischemic from non-ischemic cardiomyopathy is important because patients with ischemic cardiomyopathy can potentially have dramatic improvement with revascularization. Single photon emission computed tomography (SPECT) has excellent reported sensitivity and negative predictive value in the detection of coronary artery disease in HF patients. SPECT imaging is also useful in establishing treatment strategies in patients with HF, including those with new onset CHF. Cardiac neuronal imaging of mIBG is particularly helpful in risk stratification of patients with HF. The modality can be used to monitor the response to therapy as dysfunctional mIBG uptake may show improvement with pharmacological treatment.

J Nucl Cardiol: 29 Aug 2013; epub ahead of print

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

Aljaroudi WA, Desai MY, Tang WH, Phelan D, Cerqueira MD, Jaber WA
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.

J Nucl Cardiol: 17 Dec 2013; epub ahead of print

Asystole following regadenoson infusion in stable outpatients.

Rosenblatt J, Mooney D, Dunn T, Cohen M
Regadenoson is a selective A2A receptor agonist approved for use as a pharmacologic stress agent for myocardial perfusion imaging after several multicenter trials demonstrated its equivalence in diagnostic accuracy for the detection of coronary artery disease and a decreased incidence of serious side effects as compared to adenosine. Recently, the FDA released a safety announcement advising of the rare but serious risk of heart attack and death associated with regadenoson and adenosine in cardiac stress testing, particularly in patients with unstable angina or cardiovascular instability. We report two cases of asystole with hemodynamic collapse in stable outpatients soon after receiving a standard regadenoson injection. The prevalence of potentially life threatening bradycardia, including asystole, associated with the use of regadenoson may be greater than previously expected. These cases highlight the need for cardiac stress labs to anticipate the potential for serious side effects with all patients during the administration of coronary vasodilators.

J Nucl Cardiol: 30 May 2014; epub ahead of print

Diagnostic accuracy of 64-slice computed tomography coronary angiography for the detection of in-stent restenosis: A meta-analysis.

Carrabba N, Schuijf JD, de Graaf FR, Parodi G, ... Antoniucci D, Bax JJ
Background: We sought to evaluate the diagnostic accuracy of 64-slice multi-detector row computed tomography (MDCT) compared with invasive coronary angiography for in-stent restenosis (ISR) detection. Methods: MEDLINE, Cochrane library, and BioMed Central database searches were performed until April 2009 for original articles. Inclusion criteria were (1) 64-MDCT was used as a diagnostic test for ISR, with >50% diameter stenosis selected as the cut-off criterion for significant ISR, using invasive coronary angiography and quantitative coronary angiography as the standard of reference; (2) absolute numbers of true positive, false positive, true negative, and false negative results could be derived. Standard meta-analytic methods were applied. Results: Nine studies with a total of 598 patients with 978 stents included were considered eligible. On average, 9% of stents were unassessable (range 0-42%). Accuracy tests with 95% confidence intervals (CIs) comparing 64-MDCT vs invasive coronary angiography showed that pooled sensitivity, specificity, positive and negative likelihood ratio (random effect model) values were: 86% (95% CI 80-91%), 93% (95% CI 91-95%), 12.32 (95% CI 7.26-20.92), 0.18 (95% CI 0.12-0.28) for binary ISR detection. The symmetric area under the curve value was 0.94, indicating good agreement between 64-MDCT and invasive coronary angiography. Conclusions: 64-MDCT has a good diagnostic accuracy for ISR detection with a particularly high negative predictive value. However, still a relatively large proportion of stents remains uninterpretable. Accordingly, only in selected patients, 64-MDCT may serve as a potential alternative noninvasive method to rule out ISR.

J Nucl Cardiol: 09 Apr 2010; epub ahead of print

A comparison of the image quality of full-time myocardial perfusion SPECT vs wide beam reconstruction half-time and half-dose SPECT.

Depuey EG, Bommireddipalli S, Clark J, Leykekhman A, Thompson LB, Friedman M
ObjectiveS: Wide Beam Reconstruction (WBR) (UltraSPECT, Ltd) uses resolution recovery and noise modeling to cope with decreased SPECT count statistics. Because WBR processing reconstructs half the usual SPECT count statistics, we postulate that image quality equivalent to a full-time acquisition can be achieved in either half the time or with half the radiopharmaceutical activity. Methods: In 156 consecutive patients (pts) rest and 8-frame gated post-stress myocardial perfusion SPECT was performed following 333-444 and 1184-1480 MBq (9-12 and 32-40 mCi) Tc-99m sestamibi injections, respectively, with full-time (rest = 14 min; stress = 12.3 min) acquisitions processed with OSEM and also separate "half-time" acquisitions processed with WBR. A subsequent group of 160 consecutive pts matched in gender, weight, and chest circumference received "half-dose" rest and stress injections 214.6 ± 22.2 and 647.5 ± 92.5 MBq (5.8 ± 0.6 and 17.5 ± 2.5 mCi) with full-time SPECT acquisitions. Image quality (1 = poor to 5 = excellent) was judged by myocardial count density and uniformity, endocardial edge definition, perfusion defect delineation, right ventricular visualization, and background noise. Results: Mean image quality for rest, stress, and post-stress gated images were 3.6 ± 0.7, 3.8 ± 0.7, and 3.9 ± 1.0, respectively, for "full-time OSEM; 3.7 ± 0.8, 4.0 ± 0.7, and 4.8 ± 0.4 for "half-time" WBR; and 4.3 ± 0.8, 4.6 ± 0.6, and 4.7 ± 0.6 for "half-dose" WBR. "Half-time" and "half-dose" WBR image quality were both superior to standard full-time OSEM (P\'s < .001). There was no significant difference between the summed stress and rest scores for "full-time" OSEM vs "half-time" WBR in 82 patients with perfusion defects. Conclusions: Both "half-time" and "half-dose" WBR provide myocardial perfusion SPECT quality superior to full-time OSEM, with an associated decrease in scan acquisition time and patient radiation exposure, respectively.

J Nucl Cardiol: 02 Feb 2011; epub ahead of print

Myocardial imaging with (99m)Tc-Tetrofosmin: Influence of post-stress acquisition time, regional radiotracer uptake, and wall motion abnormalities on the clinical result.

Giorgetti A, Kusch A, Casagranda M, Tagliavia ID, Marzullo P
Background: We previously demonstrated that early (15\', T1) post-stress myocardial imaging with Tetrofosmin could be more accurate than standard acquisitions (45\', T2) in identifying coronary artery disease. Methods and results: To clarify this phenomenon, 120 subjects (age 61 +/- 10 years) with both T1 and T2 scans were divided into Group 1 (53/120 pts) with more ischemia at T1 vs T2 imaging (T1-T2SDS >/= 3); Group 2 (67/120 pts) with similar results (T1-T2SDS </= 2). Myocardial areas were categorized as control nonischemic, ischemic, and scarred on the basis of perfusion/contraction properties and coronary anatomy. In each area, regional myocardial count statistic and semiquantitative wall motion/thickening values were obtained. Analysis of T1 and T2 post-stress myocardial counts demonstrated a significant Tetrofosmin wash-out rate that was higher in Group 1 control nonischemic regions (15 +/- 8% vs 13.6 +/- 9.6%, P < .02), significantly lower in Group 1 ischemic regions (7 +/- 10% vs 12.2 +/- 9.5%, P < .0001), and comparable between scarred areas of the two groups (P = NS). Delta post-stress wall thickening (T1-T2) was lower in Group 1 ischemic regions (-4.5 +/- 9.15% vs -1.90 +/- 7.0%, P < .001) and comparable in both control nonischemic and scarred areas of the two groups (P = NS). Conclusion: The clinical result of Tetrofosmin gated-SPECT can be influenced by the post-stress acquisition time because of ischemic-induced regional wall thickening abnormalities and the existence of a differential radiotracer myocardial wash-out.

J Nucl Cardiol: 16 Dec 2009; epub ahead of print

Caffeine reduces the sensitivity of vasodilator MPI for the detection of myocardial ischaemia: Pro.

Reyes E
Caffeine is a non-selective antagonist at the adenosine receptors, which is expected to reverse both the intended (coronary vasodilation) and unintended (hypotension, flushing) effects of exogenously administered adenosine and adenosine-related compounds. In the past, several studies were conducted to characterize the effect of caffeine on vasodilator myocardial perfusion imaging (MPI) with conflicting results. However, new evidence supports earlier observations and shows that recent caffeine intake attenuates vasodilator-induced myocardial hyperaemia and may therefore reduce the sensitivity of radionuclide MPI for the detection of inducible perfusion abnormality in patients with coronary artery disease. Although the magnitude of this effect and hence its clinical significance are dose dependent, the acute response to equivalent doses of caffeine varies largely among individuals, and this might be explained by differences in caffeine exposure and genetically determined variations in caffeine metabolism. Abstinence from caffeinated foods and beverages for a minimum of 12 hours before vasodilator stress is therefore recommended although longer abstention might be required in order to prevent the potentially blocking effect of residual caffeine on vasodilator-mediated actions.

J Nucl Cardiol: 16 Feb 2016; epub ahead of print

Assessment of coronary endothelial function using PET.

Yoshinaga K, Manabe O, Tamaki N
Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. Several coronary risk factors adversely affect endothelial function. Therefore, a finding of endothelial dysfunction may guide interventions for preventing the development of future cardiovascular events. The non-invasive aspects and coronary specificity of measurements of myocardial blood flow (MBF) using positron emission tomography (PET) with sympathetic stress make it widely applicable for the evaluation of endothelial function. PET MBF measurements with sympathetic stress have been applied to a variety of subjects with coronary risk factors and have been shown to have value for risk assessment in these subjects. Endothelial measurement using PET remains an ideal research tool for the study of the pathophysiology of several cardiac diseases. PET is also well suited for the acute and longitudinal evaluation of treatment. Thus, the continued development of this approach for the evaluation of new treatment effects should be expected.

J Nucl Cardiol: 30 Mar 2011; epub ahead of print

Established and emerging dose reduction methods in cardiac computed tomography.

Small GR, Kazmi M, Dekemp RA, Chow BJ
Cardiac computed tomography (CT) is a non-invasive modality that is commonly used as an alternative to invasive coronary angiography for the investigation of coronary artery disease. The enthusiasm for this technology has been tempered by a growing appreciation of the potential risks of malignancy associated with the use of ionising radiation. In the spirit of minimizing patient risk, the medical profession and industry have worked hard to developed methods and protocols to reduce patient radiation exposure while maintaining excellent diagnostic accuracy. A complete understanding of radiation reduction techniques will allow clinicians to reduce patient risk while providing an important diagnostic service. This review will consider the established and emerging techniques that may be adopted to reduce patient absorbed doses from x-ray CT. By modifying (1) x-ray tube output, (2) imaging time (scan duration), (3) imaging distance (scan length) and (4) the appropriate use of shielding, clinicians will be able to adhere to the \'as low as reasonably achievable (ALARA)\' principle.

J Nucl Cardiol: 01 Jun 2011; epub ahead of print

Differentiation of malignant from benign heart and pericardial lesions using positron emission tomography and computed tomography.

Shao D, Wang SX, Liang CH, Gao Q
Objective: To assess the feasibility of (18)F-FDG PET-CT for the differentiation of malignancy from benign lesions of the heart and the pericardium. Methods: A total of 23 cases (malignancy:benign = 13:10) with cardiac and pericardial lesions, confirmed by pathology or on clinical grounds, were analyzed in this study. All lesions were evaluated semi-quantitatively using maximum standard uptake values (SUV(max)) and SUV(max) lesion/blood, and the density of the heart and pericardium lesions and the relation with surrounding tissues were evaluated. The differences of SUV(max) and SUV(max) lesion/blood between benign and malignant lesions were analyzed by the Mann-Whitney test. Subsequently, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for CT and PET-CT, respectively. Results: The maximum SUV showed significant difference between malignancy (avg ± SD 6.5) and benign (avg ± SD 1.5) (Z = -3.601, P < .01), the SUV(max) lesion/blood of malignancy and benign were avg ± SD 3.4 and avg ± SD 0.9, respectively, also with a significant difference (Z = -3.600, P < .01). In this pilot study, the optimal cutoff value to separate benign vs malignant lesions of SUV(max) was 3.5-4.0 and the cutoff for SUV(max) lesion/blood was 1.3-2.0. The sensitivity, specificity, accuracy, PPV, and NPV of CT and PET-CT were 76.9%(10/13), 100.0%(10/10), 87.0%(20/23), 100.0%(10/10), 76.9%(10/13) and 100.0%(13/13), 90.0%(9/10), 95.7%(22/23), 92.9%(13/14), 100.0%(9/9), respectively. Conclusion: (18)F-FDG PET-CT appears promising for correctly differentiating benign vs malignant cardiac and pericardial lesions.

J Nucl Cardiol: 09 Jun 2011; epub ahead of print

Relation of left-ventricular dyssynchrony by phase analysis of gated SPECT images and cardiovascular events in patients with implantable cardiac defibrillators.

Aljaroudi WA, Hage FG, Hermann D, Doppalapudi H, ... Heo J, Iskandrian AE
Background: Left-ventricular (LV) dyssynchrony could be measured by gated SPECT myocardial perfusion imaging (MPI). This study examined the relation between the degree of dyssynchrony and outcome in patients with implantable cardiac defibrillators (ICDs). Methods and results: We studied 70 patients with ICD and LV ejection fraction (EF) <.40 by gated MPI (performed within 6 weeks of the device implantation). The images were re-processed using phase analysis to derive phase standard deviation (SD) and histogram bandwidth. All-cause mortality and appropriate ICD shocks were identified as the primary endpoint. There were 87% men, aged 62 +/- 11 years. The EF was 26 +/- 8% (range 12%-39%). The phase SD was 51 degrees +/- 20 degrees (range 12 degrees -99 degrees ) and the histogram bandwidth was 157 degrees +/- 72 degrees (range 21 degrees -327 degrees ). The SD and bandwidth were significantly greater than corresponding values in patients with normal EF (15.8 +/- 11.8 degrees and 42.0 +/- 28.4 degrees , respectively, P < .0001, each). At 1 year, 8 patients (11%) died or had shocks. The patients with events had higher phase SD than those without events (60 +/- 5 degrees vs 50 +/- 21 degrees , P = .002). The histogram bandwidth was also higher in those with events (185 +/- 37 vs 154 +/- 75, P = .07). All patients with event had a phase SD >/= 50 degrees , while none of the patients with a phase SD < 50 degrees (N = 26) had an event (P = .02). Conclusions: The severity of LV dyssynchrony by phase analysis in patients with LV dysfunction, and ICD is associated with increased risk of death and appropriate ICD shock; a phase SD < 50 degrees was associated with no events at 1 year.

J Nucl Cardiol: 19 Mar 2010; epub ahead of print

Duration and type of therapy for diabetes: Impact on cardiac risk stratification with stress electrocardiographic-gated SPECT myocardial perfusion imaging.

Barmpouletos D, Stavens G, Ahlberg AW, Katten DM, O\'Sullivan DM, Heller GV
Background: Stress electrocardiogram(ECG)-gated single photon emission computed tomography (SPECT) imaging is highly effective in risk stratification of diabetic patients for adverse cardiac events. While patients with diabetes are predisposed to a more aggressive progression of vascular disease, the impact of its duration and type of therapy on risk stratification are unknown. Methods: From the Hartford Hospital Nuclear Cardiology clinical database, 886 diabetic patients who underwent exercise or pharmacologic stress ECG-gated SPECT were identified, with complete follow-up regarding the occurrence of adverse cardiac events and information regarding the duration of diabetes and the type of therapy (insulin vs oral medication only) at the time of testing. Images were interpreted using the American College of Cardiology/ASNC standard 17-segment scoring model. Results: Of the 886 diabetic patients, 98 (11%) suffered cardiac death or non-fatal myocardial infarction during follow-up (2.5 ± 1.6 years). A receiver operator characteristics curve demonstrated that diabetes ≥10 years in duration provided the maximal sum of sensitivity and specificity for the prediction of adverse cardiac outcomes. Multivariate analysis identified the following as independent predictors of adverse outcome: Post-stress ejection fraction (EF) <40% (P = .001), age (P = .004), insulin therapy (P = .031), diabetes duration >10 years (P = .038), summed stress score (SSS) >8 (P = .046). For patients with an SSS >8, diabetes duration and type of therapy significantly enhanced risk stratification. Similar findings emerged for patients with a post-stress EF <40%. Conclusion: For diabetic patients undergoing stress ECG-gated SPECT myocardial perfusion imaging, disease duration and type of therapy provide independent and incremental prognostic information. Integration of these variables with this cardiovascular imaging technology significantly enhances cardiac risk stratification.

J Nucl Cardiol: 21 Oct 2010; epub ahead of print

Treatment of patients with intermediate cardiovascular risk: Are clinical measures enough?

Bove AA, Santamore WP, Homko C, Kashem A, ... Shirk G, Menapace F
AIM: Clinical measures of cardiovascular disease risk (CVD) are important tools for establishing therapy to lower CVD risk. Risk assessment has come under criticism because clinical measures can underestimate or overestimate CVD risk. We assessed CVD risk in 252 subjects without evidence of CVD to establish therapy of one or more risk factors from clinical indications. The subjects all had intermediate CVD risk using the Framingham score. Results: Average age was 59.1 years. 23.8% were smokers, 59.1% were hypertensive, 65.1% had hyperlipidemia. BMI was greater than 30 kg/M(2) in 56% and diabetes was present in 43.7%. In this cohort, 86.9% required therapy for hypertension or hyperlipidemia, and this proportion increased to 95.6% when subjects with diabetes were included. Of the remaining 4.4% (11 subjects), 7 reached intermediate risk based on cigarette smoking and 4 based on age >65 years old. Among diabetics, 94/110 had another risk factor and would require statin and ACE or ARB therapy. Conclusions: Of subjects at intermediate risk for CVD, 98.4% would not require further testing to decide on therapy to lower CVD risk. Although 16 diabetic subjects had no other risk factors, current guidelines suggest that these subjects should be treated to reduce CVD risk.

J Nucl Cardiol: 02 Aug 2011; epub ahead of print

Predictors of an ischemic electrocardiographic response in patients with exercise-induced myocardial ischemia.

Malhotra S, Follansbee WP, Soman P
Background: The determinants of an ischemic electrocardiographic (ECG) response in patients with exercise-induced ischemia on single-photon emission computed tomography (SPECT) remain poorly defined. Specifically, it is unknown whether the occurrence of an ischemic ECG response is related to the extent and/or severity of SPECT ischemia. Methods and results: Among 3,294 patients who underwent exercise SPECT using a rest thallium-201/exercise Tc-99m sestamibi protocol, 699 (21%) patients had myocardial ischemia defined as summed difference score (SDS) ≥2. The extent of SPECT ischemia was further defined as the total number of segments with difference score ≥1, and severity of ischemia as the largest difference score among all segments. Patients with ischemic ECG changes (n = 315) were significantly older and had a significantly greater prevalence of hyperlipidemia. SDS (7.4 ± 2.2 vs 4.7 ± 1.9, P < .0001), extent (4.2 ± 2.6 vs 2.9 ± 1.7, P < .0001), and severity (2.8 ± 0.9 vs 2.3 ± 0.8, P < .0001) of SPECT ischemia were greater among patients with ischemic ECG changes. In multivariate analysis, age and SDS (which is a composite of the extent and severity of ischemia) were associated with ischemic ECG. When analyzed in a separate model which did not include SDS, both severity of SPECT ischemia (OR 1.42, CI 1.13-1.79) and extent of SPECT ischemia (OR 1.21, CI 1.10-1.33) were independently associated with ischemic ECG. Conclusions: Among patients with exercise-induced myocardial ischemia by SPECT, age and SDS were associated with ischemic ECG changes. When analyzed separately, the severity and extent of SPECT ischemia were both independent predictors of ischemic ECG changes.

J Nucl Cardiol: 14 Jun 2011; epub ahead of print

Transient ischemic dilatation ratio derived from myocardial perfusion scintigraphy: What are we looking at?

van der Veen BJ, Kuperij N, Stokkel MP
Background: Elevated transient ischemic dilatation (TID) ratio during myocardial perfusion imaging (MPI) is described as a marker of severe CAD, even in acquisitions with normal perfusion. This was initiated to explore the effects of stressor type on the TID. Additionally the relation between the TID and other functional parameters, such as end diastolic volume (EDV), end systolic volume (ESV), and left ventricle ejection fraction (LVEF), heart rate (HR), and severity of ischemia, was evaluated. METHOD: A total of 299 consecutive patients referred for a 2-day stress/rest MPI protocol were included. Patients were stressed with either adenosine (n = 164) or exercise (n = 135). MPI data were analyzed with an automated software tool to determine TID, EDV, ESV, LVEF, SSS, and SDS. The SDS was used to quantify the degree of ischemia, with a SDS >/= 3 considered ischemic. Results: Comparison of the adenosine and exercise stressed population revealed significant differences, especially in parameters derived from the poststress acquisition. Within the exercise stressed population, TID was proportional with the SDS (R (2) = .12); whereas the adenosine population did not show such a relation (R (2) = .001). Difference in HR between rest and poststress acquisitions showed high levels of linear regression with TID values of both the adenosine (R (2) = .41) and exercise (R (2) = .29) stressed population. Conclusion: In an exercise stressed population, TID is determined by both the degree of ischemia and the heart-rate difference between the two acquisition moments. TID within the adenosine population was found to be highly proportional with the HR, rather than with the degree of ischemia.

J Nucl Cardiol: 25 Dec 2009; epub ahead of print

Noninvasive assessment myocardial viability: Current status and future directions.

Allman KC
Observations of reversibility of cardiac contractile dysfunction in patients with coronary artery disease and ischemia were first made more than 40 years ago. Since that time a wealth of basic science and clinical data has been gathered exploring the mechanisms of this phenomenon of myocardial viability and relevance to clinical care of patients. Advances in cardiac imaging techniques have contributed greatly to knowledge in the area, first with thallium-201 imaging, then later with Tc-99m-based tracers for SPECT imaging and metabolic tracers used in conjunction with positron emission tomography (PET), most commonly F-18 FDG in conjunction with blood flow imaging with N-13 ammonia or Rb-82 Cl. In parallel, stress echocardiography has made great progress also. Over time observational studies in patients using these techniques accumulated and were later summarized in several meta-analyses. More recently, cardiac magnetic resonance imaging (CMR) has contributed further information in combination with either late gadolinium enhancement imaging or dobutamine stress. This review discusses the tracer and CMR imaging techniques, the pooled observational data, the results of clinical trials, and ongoing investigation in the field. It also examines some of the current challenges and issues for researchers and explores the emerging potential of combined PET/CMR imaging for myocardial viability.

J Nucl Cardiol: 16 Jun 2013; epub ahead of print

Tako-tsubo cardiomyopathy: How to understand possible pathophysiological mechanism and the role of (123)I-MIBG imaging.

Verschure DO, Somsen GA, van Eck-Smit BL, Knol RJ, Booij J, Verberne HJ
Tako-tsubo cardiomyopathy (TCM) is an increasingly recognized clinical syndrome characterized by acute reversible apical ventricular dysfunction, commonly preceded by exposure to severe physical or emotional stress. In this review, we give a short overview on clinical presentation and treatment of TCM and discuss the possible pathophysiological mechanisms of TCM and the role of various non-invasive imaging modalities in TCM with a focus on the potential role of (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy. Currently, the dominating hypothesis on the pathophysiology of TCM postulates that high levels of the neurotransmitter epinephrine may trigger a change in intracellular signaling in ventricular myocytes. More specific, epinephrine stimulates G-protein coupled β2 adenoreceptors (β2AR) which are located on ventricular myocytes. Normal levels of this neurotransmitter predominantly stimulate the intracellular G-protein, and induce a positive inotropic effect. However, with significant increasing levels of epinephrine, the predominance of stimulation is shifted from G-stimulating to the G-inhibitor protein coupling, which leads to a negative inotropic effect. Interestingly, this negative inotropic effect is the largest in the apical myocardium where the β2AR:β1AR ratio is the highest within the heart. Echocardiography and ventriculography are essential to diagnose TCM, but new imaging tools are promising to diagnose TCM and to evaluate therapeutic efficacy. Cardiovascular magnetic resonance can be used to differentiate TCM from other myocardial diseases, such as myocarditis. (123)I-meta-iodobenzylguanidine ((123)I-MIBG) scintigraphy can be used to assess ventricular adrenergic activity and may guide optimization of individual (pharmacological) therapy. These new insights into the possible pathophysiological mechanisms and novel diagnostic imaging modalities can be used as starting point for the development of international guidelines of TCM which may increase the awareness, and optimize the treatment of TCM.

J Nucl Cardiol: 26 Jan 2014; epub ahead of print

High-efficiency SPECT MPI: Comparison of automated quantification, visual interpretation, and coronary angiography.

Duvall WL, Slomka PJ, Gerlach JR, Sweeny JM, ... George T, Henzlova MJ
Background: Recently introduced high-efficiency (HE) SPECT cameras with solid-state CZT detectors have been shown to decrease imaging time and reduce radiation exposure to patients. An automated, computer-derived quantification of HE MPI has been shown to correlate well with coronary angiography on one HE SPECT camera system (D-SPECT), but has not been compared to visual interpretation on any of the HE SPECT platforms. Methods: Patients undergoing a clinically indicated Tc-99m sestamibi HE SPECT (GE Discovery 530c with supine and prone imaging) study over a 1-year period followed by a coronary angiogram within 2 months were included. Only patients with a history of CABG surgery were excluded. Both MPI studies and coronary angiograms were reinterpreted by blinded readers. One hundred and twenty two very low (risk of CAD < 5%) or low (risk of CAD < 10%) likelihood subjects with normal myocardial perfusion were used to create normal reference limits. Computer-derived quantification of the total perfusion deficit at stress and rest was obtained with QPS software. The visual and automated MPI quantification were compared to coronary angiography (≥70% luminal stenosis) by receiver operating curve (ROC) analysis. Results: Of the 3,111 patients who underwent HE SPECT over a 1-year period, 160 patients qualified for the correlation study (66% male, 52% with a history of CAD). The ROC area under the curve (AUC) was similar for both the automated and the visual interpretations using both supine only and combined supine and prone images (0.69-0.74). Using thresholds determined from sensitivity and specificity curves, the automated reads showed higher specificity (59%-67% vs 27%-60%) and lower sensitivity (71%-72% vs 79%-93%) than the visual reads. By including prone images sensitivity decreased slightly but specificity increased for both. By excluding patients with known CAD and cardiomyopathies, AUC and specificity increased for both techniques (0.72-0.82). The use of a difference score to evaluate ischemic burden resulted in lower sensitivities but higher specificities for both automated and visual quantification. There was good agreement between the visual interpretation and automated quantification in the entire cohort of 160 unselected consecutive patients (r = 0.70-0.81, P < .0001). Conclusions: Automated and visual quantification of high-efficiency SPECT MPI with the GE Discovery camera provides similar overall diagnostic accuracy when compared to coronary angiography. There was good correlation between the two methods of assessment. Combined supine and prone stress imaging provided the best diagnostic accuracy.

J Nucl Cardiol: 04 Jun 2013; epub ahead of print

Stress-only or stress/rest myocardial perfusion imaging in patients undergoing evaluation for bariatric surgery.

Gemignani AS, Muhlebach SG, Abbott BG, Roye GD, Harrington DT, Arrighi JA
Background: Bariatric surgery for management of obesity is being used with increasing frequency. Stress testing with myocardial perfusion imaging is often employed as part of the workup prior to anticipated bariatric surgery. The incidence of clinically significant abnormalities on stress MPI performed for this indication, however, has not been established. Methods and results: We retrospectively reviewed a series of 383 consecutive stress MPI studies performed on patients undergoing workup prior to planned bariatric surgery. The study population had a mean age 42 ± 10 years, and was 83% female, with a body mass index of 49 ± 8. The majority of patients (81%) were able to exercise using either the Bruce or Modified Bruce protocol, and 67% underwent stress-only imaging. Overall SPECT MPI findings were normal in 89% and equivocal in 6% of patients. The incidence of abnormal findings on MPI was 5% (3% mild and 2% moderate-to-severe abnormalities). At 1 year, overall survival was 99.5%, with no difference between those with and without MPI abnormalities. Similarly, the incidence of post-operative cardiac events was very low (2%), and mostly due to atrial arrhythmias or borderline elevations of troponin. Conclusion: In a typical pre-bariatric surgery population, the incidence of abnormal stress MPI is low. The majority of patients were able to use a stress-only strategy for assessment of perfusion. At 1 year the incidence of adverse cardiovascular outcomes is very low. Additional studies should be focused on determining whether any subgroup of such patients may benefit more from pre-operative stress testing.

J Nucl Cardiol: 15 Jul 2011; epub ahead of print

Survival analysis and regression models.

George B, Seals S, Aban I
Time-to-event outcomes are common in medical research as they offer more information than simply whether or not an event occurred. To handle these outcomes, as well as censored observations where the event was not observed during follow-up, survival analysis methods should be used. Kaplan-Meier estimation can be used to create graphs of the observed survival curves, while the log-rank test can be used to compare curves from different groups. If it is desired to test continuous predictors or to test multiple covariates at once, survival regression models such as the Cox model or the accelerated failure time model (AFT) should be used. The choice of model should depend on whether or not the assumption of the model (proportional hazards for the Cox model, a parametric distribution of the event times for the AFT model) is met. The goal of this paper is to review basic concepts of survival analysis. Discussions relating the Cox model and the AFT model will be provided. The use and interpretation of the survival methods model are illustrated using an artificially simulated dataset.

J Nucl Cardiol: 08 May 2014; epub ahead of print

Evaluation of baseline contractile reserve vs dyssynchrony as a predictor of functional improvement and long term outcome after resynchronization pacing therapy: A radionuclide stress study.

Verna E, Ghiringhelli S, Scotti S, Caravati F
AIM: To assess the predictive value of baseline ventricular dyssynchrony and myocardial contractile reserve (mCR) in identifying responders to cardiac resynchronization therapy (CRT). Methods: We prospectively studied 57 patients selected for CRT according to current recommendations. Regional dyssynchrony was evaluated by parametric phase imaging of ecg-gated equilibrium radionuclide angiography (ERNA). The mean inter-ventricular phase delay and the standard deviation to mean left ventricular (LV) phase angle were used as a measure of inter- and intra-ventricular dyssynchrony, respectively. Change in LV ejection fraction (LVEF) during low-dose dobutamine (LDD) was measured to assess mCR. ERNA was repeated at 6 months to evaluate changes in LVEF after CRT. Combined end-points of re-hospitalization for heart failure, heart transplantation, and cardiac death were assessed over a period of 76 months (mean 43 ± 31). Results: Baseline dyssynchrony was present in most patients (85%). After CRT only one half of patients showed a reduction in intra-ventricular dyssynchrony and 33% an increase in LVEF by >5%. Improvement of LVEF was not predicted by baseline LVEF, clinical presentation, dyssynchrony parameters or QRS duration. There was a significant relationship between changes in LVEF during LDD testing and after CRT (r = 0.65; P < .0001). Logistic regression analysis identified mCR as independent predictor of improvement in LVEF (P = .039; OR = 3.84; CI 95% = 1.06-13.9), resynchronization (P = .046; OR = 4.20; CI 95% = 1.03-17.2), and event-free survival (P = .002; OR = 0.10; CI 95% = 0.02-0.43). Conclusions: In patients with left ventricular dysfunction and baseline dyssynchrony as assessed by ERNA, evaluation of mCR during LDD may help predicting functional improvement and selecting potential responders to CRT.

J Nucl Cardiol: 19 Jul 2011; epub ahead of print

Increased Regional Epicardial Fat Volume Associated with Reversible Myocardial Ischemia in Patients with Suspected Coronary Artery Disease.

Khawaja T, Greer C, Thadani SR, Kato TS, ... Einstein AJ, Schulze PC
Epicardial adipose tissue is a source of pro-inflammatory cytokines and has been linked to the development of coronary artery disease. No study has systematically assessed the relationship between local epicardial fat volume (EFV) and myocardial perfusion defects. We analyzed EFV in patients undergoing SPECT myocardial perfusion imaging combined with computed tomography (CT) for attenuation correction. Low-dose CT without contrast was performed in 396 consecutive patients undergoing SPECT imaging for evaluation of coronary artery disease. Regional thickness, cross-sectional areas, and total EFV were assessed. 295 patients had normal myocardial perfusion scans and 101 had abnormal perfusion scans. Mean EFVs in normal, ischemic, and infarcted hearts were 99.8 ± 82.3 cm(3), 156.4 ± 121.9 cm(3), and 96.3 ± 102.1 cm(3), respectively (P < 0.001). Reversible perfusion defects were associated with increased local EFV compared to normal perfusion in the distribution of the right (69.2 ± 51.5 vs 46.6 ± 32.0 cm(3); P = 0.03) and left anterior descending coronary artery (87.1 ± 76.4 vs 46.7 ± 40.6 cm(3); P = 0.005). Our results demonstrate increased regional epicardial fat in patients with active myocardial ischemia compared to patients with myocardial scar or normal perfusion on nuclear perfusion scans. Our results suggest a potential role for cardiac CT to improve risk stratification in patients with suspected coronary artery disease.

J Nucl Cardiol: 22 Oct 2014; epub ahead of print

Imaging in patients after cardiac transplantation and in patients with ventricular assist devices.

Gupta B, Jacob D, Thompson R
The field of cardiac imaging and the management of patients with severe heart failure have advanced substantially during the past 10 years. Cardiac transplantation offers the best long-term survival with high quality of life for the patients with end stage heart failure. However, acute cardiac rejection and cardiac allograft vasculopathy (CAV) can occur post cardiac transplantation and these problems necessitate regular surveillance. The short-term success of mechanical circulatory support devices (MCSD), such as ventricular assist devices (VADs), in improving survival and quality of life has led to a dramatic growth of the patient population with these devices. The development of optimal imaging techniques and algorithms to evaluate these advanced heart failure patients is evolving and multimodality non-invasive imaging approaches and invasive techniques are commonly employed. Most of the published studies done in the transplant and VAD population are small, and biased based on the strength of the particular program, and there is a relative lack of published protocols to evaluate these patient groups. Moreover, the techniques of echocardiography, computed tomography (CT), magnetic resonance imaging, and nuclear cardiology have all progressed rapidly in recent years. There is thus a knowledge gap for cardiologists, radiologists, and clinicians, especially regarding surveillance for CAV and ideal imaging approaches for patients with VADs. The purpose of this review article is to provide an overview of different noninvasive imaging modalities used to evaluate patients after cardiac transplantation and for patients with VADs. The review focuses on the role of echocardiography, CT, and nuclear imaging in surveillance for CAV and rejection and on the assessment of ventricular structure and function, myocardial remodeling and complications for VAD patients.

J Nucl Cardiol: 01 Apr 2015; epub ahead of print

Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA.

Phillips LM, Hachamovitch R, Berman DS, Iskandrian AE, ... Maron DJ, Shaw LJ
There is a preponderance of evidence that, in the setting of an acute coronary syndrome, an invasive approach using coronary revascularization has a morbidity and mortality benefit. However, recent stable ischemic heart disease (SIHD) randomized clinical trials testing whether the addition of coronary revascularization to guideline-directed medical therapy (GDMT) reduces death or major cardiovascular events have been negative. Based on the evidence from these trials, the primary role of GDMT as a front line medical management approach has been clearly defined in the recent SIHD clinical practice guideline; the role of prompt revascularization is less precisely defined. Based on data from observational studies, it has been hypothesized that there is a level of ischemia above which a revascularization strategy might result in benefit regarding cardiovascular events. However, eligibility for recent negative trials in SIHD has mandated at most minimal standards for ischemia. An ongoing randomized trial evaluating the effectiveness of randomization of patients to coronary angiography and revascularization as compared to no coronary angiography and GDMT in patients with moderate-severe ischemia will formally test this hypothesis. The current review will highlight the available evidence including a review of the published and ongoing SIHD trials.

J Nucl Cardiol: 20 Aug 2013; epub ahead of print

Myocardial viability as integral part of the diagnostic and therapeutic approach to ischemic heart failure.

Bax JJ, Delgado V
Chronic heart failure is a major public-health problem with a high prevalence, complex treatment, and high mortality. A careful and comprehensive analysis is needed to provide optimal (and personalized) therapy to heart failure patients. The main 4 non-invasive imaging techniques (echocardiography, magnetic resonance imaging, multi-detector-computed tomography, and nuclear imaging) provide information on cardiovascular anatomy and function, which form the basis of the assessment of the pathophysiology underlying heart failure. The selection of imaging modalities depends on the information that is needed for the clinical management of the patients: (1) underlying etiology (ischemic vs non-ischemic); (2) in ischemic patients, need for revascularization should be evaluated (myocardial ischemia/viability?); (3) left ventricular function and shape assessment; (4) presence of significant secondary mitral regurgitation; (5) device therapy with cardiac resynchronization therapy and/or implantable cardiac defibrillator (risk of sudden cardiac death). This review is dedicated to assessment of myocardial viability, however "isolated assessment of myocardial viability" may be clinically not meaningful and should be considered among all those different variables. This complete information will enable personalized treatment of the patient with ischemic heart failure.

J Nucl Cardiol: 02 Mar 2015; epub ahead of print

Appropriateness of referrals for single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in a developing community: A comparison between 2005 and 2009 versions of ACCF/ASNC appropriateness criteria.

Gholamrezanezhad A, Shirafkan A, Mirpour S, Rayatnavaz M, ... Hassanpour S, Ramezani M
Introduction: Appropriateness of referrals for myocardial perfusion imaging (MPI) in developing countries has not been extensively studied. Our study was conducted to describe the ordering practices of physicians and appropriateness of MPI referrals in Iran. METHOD: We prospectively applied 2005 and 2009 versions of the Appropriateness Use Criteria published by the American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC) to 291 consecutive patients (age 55.3 ± 10.3 years) who underwent SPECT-MPI. For this purpose, we convened a panel, consisting of two academic cardiologists, one academic clinician in internal medicine, and one academic clinician in nuclear medicine. The panelists were invited for a face-to-face meeting to judge appropriateness of SPECT-MPI and independently assign a specific indication (scenario), whenever possible, for each case in accordance with ACCF/ASNC appropriateness scenarios. Results: Based on the 2005 ACCF/ASNC criteria, SPECT-MPI studies were judged appropriate for 211 (72.5%), uncertain for 36 (12.4%), inappropriate for 32 (11.0%), and unclassifiable for 12 (4.1%) referrals. The same figures based on the 2009 version were 219 (75.3%), 15 (5.2%), 49 (16.8%), and 8 (2.7%) patients, respectively. Overall agreement between the 2005 and 2009 versions was good (κ 0.63). Lack of chest pain and age below 60 years were significant indicators increasing the likelihood of inappropriate referrals by 2.9-3.4 fold. Absence of diabetes mellitus and hypertension, a normal lipid profile, lack of a past history of myocardial infarction or cardiovascular interventions (CABGs or PCI), as well as lack of application and exercise ECG stress test as the gate keeper (keeping abnormal ETT or inability of the patient to perform exercise as the appropriate indication for SPECT-MPI referral) were significant indicators, decreasing the odds of appropriate referrals. Generally a higher percentage of referrals with inappropriate indications had normal MPI. Conclusion: Our study provides an evidence for the fact that SPECT-MPI ordering practices in our developing community largely parallel the ACCF/ASNC recommendations. The implementation of appropriateness criteria is feasible in clinical settings and might provide an alternative to utilization management.

J Nucl Cardiol: 05 Aug 2011; epub ahead of print

Quantification of myocardial perfusion SPECT studies in Chinese population with Western normal databases.

Li D, Li D, Feng J, Yuan D, Cao K, Chen J
Background: The purpose of this study is to assess diagnostic performance of the current quantification packages using Western normal databases in detecting coronary artery disease in Chinese population. Methods: Seventy-five patients who underwent rest/stress myocardial perfusion SPECT and coronary angiography (CAG) were enrolled. Emory Cardiac Toolbox (ECTb) and Quantitative Perfusion SPECT (QPS) with its standard (QPS-standard) and simplified (QPS-simplified) methods were used to quantify these studies. A preliminary Chinese normal database was created from 80 normal subjects (QPS-simplified-Chinese). Receiver operator characteristic (ROC) was used to assess the accuracy of the four normal databases in detecting >/=50% or >/=70% stenosis given by CAG. Results: The enrolled cohorts had lower body mass index (BMI) and smaller heart size than Western population. The areas under ROC curve of ECTb, QPS-standard, and QPS-simplified were significantly lower than QPS-simplified-Chinese in detecting >/=50% stenosis, but not in detecting >/=70% stenosis. Diagnostic accuracy was much lower in the RCA and LCX territory. Conclusion: Chinese normal database is needed for accurately applying these quantification methods to Chinese population, especially for detecting moderate defects in regions with relatively greater attenuation impact. An alternative approach could be modification of the existing Western normal databases for low-BMI and/or small-heart subjects.

J Nucl Cardiol: 18 Mar 2010; epub ahead of print

An investigation of potential sources of artifacts in SPECT-CT myocardial perfusion studies.

Celler A, Shcherbinin S, Hughes T
Background: The increased use of hybrid SPECT-CT systems in myocardial perfusion imaging calls for a careful review of protocols that are employed in data acquisition and processing. Our study investigates the cases of potential false perfusion defects that may appear in cardiac images reconstructed with CT-based attenuation correction and high-resolution acquisition matrix. Methods: Phantom experiments performed on Infinia-Hawkeye (GE Healthcare) modeling patients with normal hearts and different body sizes and shapes were reconstructed using standard ordered subsets expectation maximization (OSEM) method with 10 subsets and 2-50 iterations. The CT-based attenuation correction (AC) with and without distance-dependent resolution recovery (RR) were employed. Results: Images reconstructed from scans with a standard thorax phantom did not show any artifacts. However, some images reconstructed from the data with extra water bags (modeling high and non-uniformly distributed attenuation) clearly displayed false perfusion defects. A potential for creating such artifacts was especially high in complex reconstruction cases. In most cases, the severity of defects decreased when reconstructions with more iterations were used. Conclusions: In situations with strong and non-uniform attenuation, the reconstruction methods with sophisticated data processing (large matrix size, AC + RR corrections) may require substantially more processing than is currently used and/or recommended.

J Nucl Cardiol: 16 Dec 2009; epub ahead of print

The coronary calcium treadmill test: A new approach to the initial workup of patients with suspected coronary artery disease.

Rozanski A, Cohen R, Uretsky S
Due to the growth of cardiac testing and increasing cost of cardiovascular healthcare, the development of more cost-effective strategies has now become a dominant issue regarding future utilization of cardiac imaging procedures. To that end, we review the potential of combining two relatively inexpensive tests, the coronary artery calcium (CAC) scan and exercise electrocardiography (ECG), as a first-line test for the workup of patients with suspected coronary artery disease (CAD). The CAC scan was initially introduced as a screening test for CAD, based on data indicating that it is a specific marker for atherosclerosis, predicts clinical risk in accordance with the magnitude of CAC, and provides incremental information for prognostic risk compared to more readily available clinical data. However, CAC scores also predict the likelihood of observing myocardial ischemia among patients undergoing exercise myocardial perfusion SPECT imaging. Exercise ECG predicts clinical events according to the ST-segment response and according to functional exercise capacity, with the latter parameter as a stronger predictor of clinical outcomes. Like CAC scores, exercise functional capacity can also be used to predict the likelihood of ischemia since ischemia diminishes proportionally with increasing exercise capacity. Recent work indicates that when patients are designated by Bayesian analyses into low, intermediate, and high likelihood categories for CAD based on clinical data and the response to exercise ECG, the frequency of inducible myocardial ischemia is very low among both low and intermediate CAD likelihood patients who have a CAC score <400. Future studies are needed to investigate what clinical factors might further modify the CAC-ischemia relationship. On the basis of current data, an initial testing strategy that employs the combined calcium treadmill test has the inherent ability to designate a substantial number of intermediate likelihood patients who would not require further testing due to relatively low CAC scores and reasonable functional capacity.

J Nucl Cardiol: 25 Aug 2013; epub ahead of print

Main pulmonary artery diameter from attenuation correction CT scans in cardiac SPECT accurately predicts pulmonary hypertension.

Burger IA, Husmann L, Herzog BA, Buechel RR, ... Russi EW, Kaufmann PA
ObjectiveS: To establish the value of the main pulmonary artery (MPA) diameter assessed from unenhanced computer tomography (CT) scans used for attenuation correction (AC) of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to predict pulmonary hypertension (PHT). Background: In contrast-enhanced chest CT scans an MPA diameter of 29 mm or greater is an established predictor of PHT. However, it is unknown, whether measurements from an unenhanced CT scan for AC may be used as predictor of PHT. Methods: 100 patients underwent SPECT MPI for assessment of coronary artery disease. PHT was defined as a right ventriculo-atrial gradient of 30 mm Hg or greater by Doppler echocardiography. We compared MPA diameter from CT to SPECT findings (right ventricular hypertrophy/enlargement, septal wall motion abnormality/perfusion defect, and D-shape) to determine the best predictor of PHT. Results: PHT was found in 37 patients. An MPA diameter of 30 mm or greater yielded a sensitivity, specificity, accuracy, positive, and negative predictive value of 78%, 91%, 86%, 83%, and 88%, respectively. This yielded an area under the ROC curve of 0.85. Conclusions: MPA diameter from low-dose unenhanced multi-slice CT reliably predicts PHT, providing an important added clinical value from AC for SPECT MPI.

J Nucl Cardiol: 20 Jun 2011; epub ahead of print

Proceedings of the cardiac PET summit meeting 12 may 2014: Cardiac PET and SPECT instrumentation.

Garcia EV
Advances in PET and SPECT and imaging hardware and software are vastly improving the noninvasive evaluation of myocardial perfusion and function. PET perfusion imaging has benefitted from the introduction of novel detectors that now allow true 3D imaging, and precise attenuation correction (AC). These developments have also resulted in perfusion images with higher spatial and contrast resolution that may be acquired in shorter protocols and/or with less patient radiation exposure than traditional PET or SPECT studies. Hybrid PET/CT cameras utilize transmission computed tomographic (CT) scans for AC, and offer the additional clinical advantages of evaluating coronary calcium and myocardial anatomy but at a higher cost than PET scanners that use (68)Ge radioactive line sources. As cardiac PET systems continue to improve, dedicated cardiac SPECT systems are also undergoing a profound change in their design. The scintillation camera general purpose design is being replaced with systems with multiple detectors focused on the heart yielding 5 to 10 times the sensitivity of conventional SPECT. As a result, shorter acquisition times and/or lower tracer doses produce higher quality SPECT images than were possible before. This article reviews these concepts and compares the attributes of PET and SPECT instrumentation.

J Nucl Cardiol: 30 Mar 2015; epub ahead of print

Molecular imaging with contrast enhanced ultrasound.

Chadderdon SM, Kaul S
Noninvasive cardiovascular imaging techniques are well-established for studying cardiovascular anatomy and physiology. Over the past decade contrast enhanced imaging techniques have been developed that are also able to characterize the molecular constituents of cardiovascular disease. In this regard, microbubble- and ultrasound-based techniques have the ability to assess a broad range of molecular components of cardiovascular pathology such as inflammation, recent ischemia, atherosclerosis, acute transplant rejection, angiogenesis, and thrombosis. The advantages of ultrasound- and microbubble-based approach include the ability to assess multiple molecular disease markers without exposure to ionizing radiation or prolonged imaging protocols. This review highlights the development of microbubble-based molecular imaging, describes successful experimental conditions in which they have been studied, and postulates the importance of translating this technique into the clinical practice.

J Nucl Cardiol: 14 May 2010; epub ahead of print

Effect of bismuth breast shielding on radiation dose and image quality in coronary CT angiography.

Einstein AJ, Elliston CD, Groves DW, Cheng B, ... Pozniakoff T, Brenner DJ
Background: Coronary computed tomographic angiography (CCTA) is associated with high radiation dose to the female breasts. Bismuth breast shielding offers the potential to significantly reduce dose to the breasts and nearby organs, but the magnitude of this reduction and its impact on image quality and radiation dose have not been evaluated. Methods: Radiation doses from CCTA to critical organs were determined using metal-oxide-semiconductor field-effect transistors positioned in a customized anthropomorphic whole-body dosimetry verification phantom. Image noise and signal were measured in regions of interest (ROIs) including the coronary arteries. Results: With bismuth shielding, breast radiation dose was reduced 46%-57% depending on breast size and scanning technique, with more moderate dose reduction to the heart, lungs, and esophagus. However, shielding significantly decreased image signal (by 14.6 HU) and contrast (by 28.4 HU), modestly but significantly increased image noise in ROIs in locations of coronary arteries, and decreased contrast-to-noise ratio by 20.9%. Conclusions: While bismuth breast shielding can significantly decrease radiation dose to critical organs, it is associated with an increase in image noise, decrease in contrast-to-noise, and changes tissue attenuation characteristics in the location of the coronary arteries.

J Nucl Cardiol: 09 Nov 2011; epub ahead of print

Incremental prognostic value of coronary flow reserve assessed with single-photon emission computed tomography.

Daniele S, Nappi C, Acampa W, Storto G, ... Petretta M, Cuocolo A
Background: We assessed the prognostic value of coronary flow reserve (CFR) estimated by single-photon emission computed tomography (SPECT) in patients with suspected myocardial ischemia. Methods and results: Myocardial perfusion and CFR were assessed in 106 patients using dipyridamole/rest Tc-99m sestamibi SPECT and follow-up was obtained in 103 (97%) patients. Four early revascularized patients were excluded and 99 were assigned to normal (summed stress score <3) vs abnormal myocardial perfusion and to normal (≥2.0) vs abnormal CFR. During the follow-up (5.8 ± 2.1 years), 28 patients experienced a cardiac event (cardiac death, nonfatal myocardial infarction, and late revascularization). Abnormal perfusion (P < .01) and abnormal CFR (P < .05) were independent predictors of cardiac events at Cox proportional hazard regression analysis. Also in patients with normal perfusion, abnormal CFR was associated with a higher annual event rate compared with normal CFR (5.2% vs 0.7%; P < .05). CFR data improved the prognostic power of the model including clinical and myocardial perfusion data increasing the global chi-square from 18.6 to 22.8 (P < .05). Finally, at parametric survival analysis, in patients with normal perfusion the time to achieve ≥2% risk of events was >60 months in those with normal and <12 months in those with abnormal CFR. Conclusions: Myocardial perfusion findings and CFR at SPECT imaging are both independent predictors of cardiac events. Estimated CFR provides incremental prognostic information over those obtained from clinical and myocardial perfusion data, particularly in patients with normal perfusion findings.

J Nucl Cardiol: 31 May 2011; epub ahead of print

Stress-only SPECT myocardial perfusion imaging: A review.

Gowd BM, Heller GV, Parker MW
Myocardial perfusion imaging (MPI) has enjoyed considerable success for decades due to its diagnostic accuracy and wealth of prognostic data. Despite this success several limitations such as lengthy protocols and radiation exposure remain. Advancements to address these shortcomings include abbreviated stress-only MPI (SO MPI) protocols, PET and both hardware and software methods to reduce radiation exposure and time. SO MPI has advantages in protocol time and radiation reduction with a wealth of supporting data in terms of diagnostic validity and prognostic value. Newer technologies such as attenuation correction, and advanced camera technologies have enabled SO MPI to be more efficient in reducing the time of acquisition and radiation dose and improving accuracy. This review examines the literature available, regarding accuracy, patient outcomes, implementation strategies, and newer developments associated with SO MPI.

J Nucl Cardiol: 08 Jul 2014; epub ahead of print

Soft tissue attenuation patterns in stress myocardial perfusion SPECT images: A comparison between supine and upright acquisition systems.

Chawla D, Rahaby M, Amin AP, Vashistha R, ... Martinez HX, Doukky R
Background: Soft tissue attenuation patterns and their interaction with body habitus and gender in Single Photon Emission Computed Tomography (SPECT)-myocardial perfusion imaging (MPI) of upright patient-position acquisition systems are not well described. Methods: In a retrospective cross-sectional study, we compared the prevalence and patterns of soft tissue attenuation in two groups of normal SPECT-MPI studies acquired by supine (n = 263) vs upright (n = 212) acquisition systems. Results: Attenuation patterns observed in the study population were: anterior (22.3%), inferior (51.6%) and lateral (18.1%). Anterior attenuation was significantly less in those imaged upright (6.1% vs 35.4%), P < .001; particularly among women (9.5% vs 50.7%), P < .001. Inferior attenuation was more common among women imaged upright (49.5% vs 13.5%), P < .001; but was not affected by imaging position among men. Lateral attenuation was more prevalent in the upright group (24.1% vs 13.3%), P = .002; and had a strong association with female gender (P < .001) and BMI ≥ 30 (P < .001). Conclusions: Upright SPECT-MPI acquisition is associated with a unique attenuation pattern which is vastly different than the supine position. Female gender strongly impacted this attenuation pattern, particularly obese women. Our study is the first to describe, in details, the attenuation patterns with upright imaging and is critical for the accurate interpretation of SPECT-MPI acquired with upright systems.

J Nucl Cardiol: 14 Jan 2011; epub ahead of print

Comparison of attenuation, dual-energy-window, and model-based scatter correction of low-count SPECT to (82)Rb PET/CT quantified myocardial perfusion scores.

Wells RG, Soueidan K, Timmins R, Ruddy TD
Background: New reconstruction algorithms allow reduction in acquisition times or the amount of injected radioactivity. We examined the impact of different corrections on low-count clinical SPECT myocardial perfusion images (MPI) and compared to (82)Rb PET/CT. We compared no corrections (NC) to attenuation correction (AC) with and without scatter correction by either a dual-energy-window (AC-DEW) or model-based (AC-ESSE) approach. All reconstructions included resolution recovery. Methods: 56 Patients were imaged using a standard rest/stress Tc-99m-tetrofosmin MPI SPECT/CT protocol with an additional half-time acquisition. A (82)Rb-rest/stress PET/CT MPI was acquired within 4 weeks. Reconstruction methods were compared using summed rest/stress/difference scores from an objective algorithm (SRS/SSS/SDS). Results: The SRS and SSS for NC were significantly (P < .01) higher than for AC, but well correlated (r ≥ 0.87). The correlation in SRS/SSS among AC, AC-DEW, and AC-ESSE was excellent (r ≥ 0.98). AC-ESSE and AC-DEW had higher SRS (P ≤ .05) than AC, but the SDS values were not significantly different. Concordance with PET normal/abnormal classification was 76% for NC and ≥85% for the AC methods. Conclusion: AC significantly improves the accuracy of low-count myocardial perfusion SPECT half-time imaging for the detection of disease compared to NC. Compared to PET, there was no significant difference among AC, AC-DEW, and AC-ESSE.

J Nucl Cardiol: 04 Jun 2013; epub ahead of print

Non-contrast cardiac computed tomography can accurately detect chronic myocardial infarction: Validation study.

Gupta M, Kadakia J, Hacioglu Y, Ahmadi N, ... Yamada G, Budoff M
Background: This study evaluates whether non-contrast cardiac computed tomography (CCT) can detect chronic myocardial infarction (MI) in patients with irreversible perfusion defects on nuclear myocardial perfusion imaging (MPI). Methods: One hundred twenty-two symptomatic patients with irreversible perfusion defect (N = 62) or normal MPI (N = 60) underwent coronary artery calcium (CAC) scanning. MI on these non-contrast CCTs was visually detected based on the hypo-attenuation areas (dark) in the myocardium and corresponding Hounsfield units (HU) were measured. Results: Non-contrast CCT accurately detected MI in 57 patients with irreversible perfusion defect on MPI, yielding a sensitivity of 92%, specificity of 72%, negative predictive value (NPV) of 90%, and a positive predictive value (PPV) of 77%. On a per myocardial region analysis, non-contrast CT showed a sensitivity of 70%, specificity of 85%, NPV of 91%, and a PPV of 57%. The ROC curve showed that the optimal cutoff value of LV myocardium HU to predict MI on non-contrast CCT was 21.7 with a sensitivity of 97.4% and specificity of 99.7%. Conclusion: Non-contrast CCT has an excellent agreement with MPI in detecting chronic MI. This study highlights a novel clinical utility of non-contrast CCT in addition to assessment of overall burden of atherosclerosis measured by CAC.

J Nucl Cardiol: 03 Dec 2010; epub ahead of print

Safety of regadenoson in patients with end-stage liver disease.

Aljaroudi W, Iqbal F, Koneru J, Bhambhvani P, Heo J, Iskandrian AE
Background: Regadenoson is a selective A(2A) receptor agonist that is used for vasodilator stress myocardial perfusion imaging (MPI). Since the drug is partially metabolized by the liver, its safety in patients with end-stage liver disease (ESLD) needs to be determined. Methods and results: We studied 168 consecutive patients with ESLD who had regadenoson stress gated single photon emission computed tomography MPI between January 2008 and March 2010 before planned orthotopic liver transplantation and compared the hemodynamic responses and safety profile to 168 control patients. There were 72 women (43%) in ESLD versus 87 (52%) in the control group (P = .1). The patients with ESLD were younger (58 ± 7 vs 62 ± 12 years, P = .0002), but more likely to be Caucasians (P = .002). The MPI images were normal in 161 patients (96%) in each group. The left ventricular ejection fraction was 72 ± 10% in ESLD and 66 ± 11% in the control patients (P = .0001). The heart rate increase in response to regadenoson was lower in patients with ESLD than in the control group (16 ± 11 vs 23 ± 16 bpm, P = .0001), but the changes in systolic and diastolic blood pressures were similar (-9 ± 12 vs -11 ± 14 mmHg and -6 ± 8 vs -7 ± 10 mmHg, respectively, P = NS). There were no deaths or medication-related adverse events that required hospitalization in either group within 30 days of the study. Conclusion: This is the first study to document the tolerability and safety profile of regadenoson in patients with ESLD.

J Nucl Cardiol: 17 Sep 2010; epub ahead of print