Mark I. Travin

ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers

1. Treadmill exercise is the most widely used stress modality. Several treadmill exercise protocols are described which differ in the speed and grade of treadmill inclination and may be more appropriate for specific patient populations. The Bruce and modified Bruce protocosls are the most widely used exercise protocols. 2. Upright bicycle exercise is commonly used in Europe. This is preferable if dynamic first-pass imaging is planned during exercise. Supine or semisupine exercise is relatively suboptimal and should only be used while performing exercise radionuclide angiocardiography.

A Pooled Analysis of Multicenter Cohort Studies of 123I-mIBG Imaging of Sympathetic Innervation for Assessment of Long-Term Prognosis in Heart Failure

OBJECTIVES The study objectives were to create a cardiac metaiodobenzylguanidine (mIBG) database using multiple prospective cohort studies and to determine the quantitative iodine-123-labeled mIBG indices for identifying patients with chronic heart failure (HF) at greatest and lowest risk of lethal events. BACKGROUND Although the prognostic value of cardiac mIBG imaging in patients with HF has been shown, clinical use of this procedure has been limited. It is required to define universally accepted quantitative thresholds for high and low risk that could be used as an aid to therapeutic decision-making using a large cohort database. METHODS Six prospective HF cohort studies were updated, and the individual datasets were combined for the present patient-level analysis. The database consisted of 1,322 patients with HF followed up for a mean interval of 78 months. Heart-to-mediastinum ratio (HMR) and washout rate of cardiac mIBG activity were the primary cardiac innervation markers. The primary outcome analyzed was all-cause death. RESULTS Lethal events were observed in 326 patients, and the population mortality rate was 5.6%, 11.3%, and 19.7% at 1, 2, and 5 years, respectively. Multivariate Cox proportional hazard model analysis for all-cause mortality identified age (p < 0.0001), New York Heart Association (NYHA) functional class (p < 0.0001), late HMR of cardiac mIBG activity (p < 0.0001), and left ventricular ejection fraction (LVEF) (p = 0.0029) as significant independent predictors. Analysis of the 512-patient subpopulation with B-type natriuretic peptide (BNP) results showed BNP (p < 0.0001), greater NYHA functional class (p = 0.0002), and late HMR (p = 0.0011) as significant predictors, but LVEF was not. The receiver-operating characteristic-determined threshold of HMR (1.68) identified patients at significantly increased risk in any LVEF category. Survival rates decreased progressively with decreasing HMR, with 5-year all-cause mortality rates >7% annually for HMR <1.25, and <2% annually for HMR ≥1.95. Addition of HMR to clinical information resulted in a significant net reclassification improvement of 0.175 (p < 0.0001). CONCLUSIONS Pooled analyses of independent cohort studies confirmed the long-term prognostic value of cardiac mIBG uptake in patients with HF independently of other markers, such as NYHA functional class, BNP, and LVEF, and demonstrated that categoric assessments could be used to define meaningful thresholds for lethal event risk.

ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures

a Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD b Department of Radiology, University of California–San Francisco, San Francisco, CA c Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Canada d Pat and Jim Calhoun Cardiology Center, UConn Health, Farmington, CT e Department of Radiology, Vanderbilt University Medical Center, Nashville, TN f Division of Nuclear Medicine, Brigham and Women’s Hospital, Boston, MA g Division of Nuclear Medicine, Washington University School of Medicine, St. Louis, MO h Turku PET Centre, Turku University Hospital, Turku, Finland i Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA j Department of Radiology, Montefiore Medical Center, Bronx, NY

Pharmacological stress testing.

Pharmacological stress in conjunction with radionuclide myocardial perfusion imaging has become a widely used noninvasive method of assessing patients with known or suspected coronary artery disease. In the United States, over one third of perfusion imaging studies are performed with pharmacological stress. Pharmacological stress agents fall into two categories: coronary vasodilating agents such as dipyridamole and adenosine, and cardiac positive inotropic agents such as dobutamine and arbutamine. For both, in the presence of coronary artery disease (CAD), perfusion image abnormalities result from heterogeneity of coronary blood flow reserve. Vasodilating agents work directly on the coronary vessels to increase blood flow, whereas inotropic agents work indirectly by increasing myocardial work load, which then leads to an increase in coronary blood flow. Both classes of agents have high accuracies for diagnosing coronary artery disease, and they have excellent safety records with acceptably low occurrences of side effects. For dipyridamole planar thallium imaging, pooled analysis yields a sensitivity of 85% and a specificity of 87% for diagnosis of coronary disease, but there is a large variation in reported values depending on various factors, such as the extent of postcatheterization referral bias, the type of imaging (planar versus single photon emission computed tomography [SPECT]), the types of patients being studied (single versus multivessel disease, men versus women), and the imaging agent used (thallium versus one of the technetium-based agents). Diagnostic accuracies for adenosine are similar to those of dipyridamole, with reported overall sensitivities ranging from 83% to 97%, and specificities ranging from 38% to 94%. For dobutamine, pooled analyses yield a sensitivity of 82% and a specificity of 75%. There is some concern that dobutamine may interfere with uptake of technetium-99m sestamibi, lowering the sensitivity for detection of disease, and thus the vasdodilating agents are generally preferred. Pharmacological stress testing has high clinical use for risk stratifying patients with known or suspected CAD, in patients after myocardial infarction, and in patients needing noncardiac surgery. Vasodilating agents are particularly advantageous in assessing post-myocardial infarction patients, allowing testing as soon as 2 days after the event. Like patients undergoing exercise stress testing, patients with normal perfusion images by pharmacological stress have a <1% annual incidence of cardiac events. The likelihood of an event increases with the extent and severity of perfusion abnormalities. However, it is important to consider clinical variables when using perfusion imaging for risk stratification, particularly in the presurgery patients. As with exercise testing, adjunct markers such as ST segment depression during testing, lung uptake of radiotracer (if thallium is used), and ventricular cavity dilatation add additional prognostic information to that available from the perfusion images alone. The aim of current research is to find better agents that are easier to use and that have fewer side effects. MRE-0470 is an experimental vasodilating agent that is more receptor selective than adenosine and promises a lower incidence of hypotension. Arbutamine more closely simulates exercise than dobutamine, and it can be administered by a closed-loop computerized delivery device. Work is also underway to look at novel uses of pharmacological stress agents, such as acquiring gated SPECT images during dobutamine infusion to enhance detection of myocardial viability. With increasing use of noninvasive testing in elderly patients and in patients with comorbidities that preclude adequate exercise, pharmacological stress testing has become an indispensable tool for radionuclide myocardial perfusion imaging studies. A good understanding of pharmacological stress testing is essential for performing high-quality nuclear cardiology

Cardiac Applications of 123I-mIBG Imaging

Cardiac autonomic innervation plays a key role in maintaining hemodynamic and electrophysiologic harmony. Cardiac sympathetic function is adversely altered in many disease states, such as congestive heart failure, myocardial ischemia, and diabetes. (123)I-mIBG, a sympathetic neurotransmitter radionuclide analog, aids in the detection of sympathetic innervation abnormalities and can be imaged with planar and single-photon emission computed tomographic techniques. Cardiac (123)I-mIBG uptake can be assessed by the heart mediastinal ratio (H/M), tracer washout rate, and focal uptake defects. These parameters have been widely studied and shown to correlate strongly and independently with congestive heart failure progression, cardiac arrhythmias, cardiac death, and all-cause mortality. There is accumulating evidence that (123)I-mIBG imaging can help to monitor a patients clinical course and response to therapy. The ability to predict potentially lethal ventricular arrhythmias promises to help more accurately select patients for implantable cardioverter defibrillators, limiting unnecessary devices and identifying additional patients at risk who do not meet current guidelines. (123)I-mIBG shows potential to help determine whether greater risk and usually more expensive ventricular assist device therapies or cardiac transplantation might be needed. Although more investigation in larger populations is needed to strengthen previous findings, cardiac (123)I-mIBG imaging shows promise as a new technique for recognizing and following potentially life-threatening cardiac conditions.

Cardiac autonomic imaging with SPECT tracers

Radionuclide cardiac imaging has potential to assess underlying molecular, electrophysiologic, and pathophysiologic processes of cardiac disease. An area of current interest is cardiac autonomic innervation imaging with a radiotracer such as 123I-meta-iodobenzylguanidine (123I-mIBG), a norepinephrine analogue. Cardiac 123I-mIBG uptake can be assessed by planar and SPECT techniques, involving determination of global uptake by a heart-to-mediastinal ratio, tracer washout between early and delayed images, and focal defects on tomographic images. Cardiac 123I-mIBG findings have consistently been shown to correlate strongly with heart failure severity, pre-disposition to cardiac arrhythmias, and poor prognosis independent of conventional clinical, laboratory, and image parameters. 123I-mIBG imaging promises to help monitor a patient’s clinical course and response to therapy, showing potential to help select patients for an ICD and other advanced therapies better than current methods. Autonomic imaging also appears to help diagnose ischemic heart disease and identify higher risk, as well as risk-stratify patients with diabetes. Although more investigations in larger populations are needed to strengthen prior findings and influence modifications of clinical guidelines, cardiac 123I-mIBG imaging shows promise as an emerging technique for recognizing and following potentially life-threatening conditions, as well as improving our understanding of the pathophysiology of various diseases.

Radionuclide imaging of cardiac autonomic innervation

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 (123I-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.

A case of Takotsubo cardiomyopathy mimicking an acute coronary syndrome

Background A 71-year-old woman presented with severe chest pain after an episode of acute emotional distress. Her serum levels of cardiac enzymes were slightly elevated and electrocardiography revealed anterior ST-segment elevations. Significant coronary stenoses were excluded. A left ventriculogram revealed apical ballooning and a hypercontractile basal segment.Investigations Serum cardiac enzyme measurements, echocardiography, coronary angiography and left ventriculography.Diagnosis Takotsubo cardiomyopathyManagement Treatment with β-blockers, aspirin, angiotensin-converting-enzyme inhibitors, and intravenous diuretics.

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

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. 123I-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 123I-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.

Cardiac Neuronal Imaging at the Edge of Clinical Application

Cardiac neuronal innervation plays an important role in normal cardiac function and is adversely affected in the presence of disease. In particular, radiotracer imaging of cardiac sympathetic function has been extensively investigated and not only provides a method of assessing the severity of disease but also has repeatedly been shown to be prognostically useful with a potential for helping to guide patient management. SPECT imaging of myocardial uptake of (123)I-mIBG, an analog of the sympathetic neurotransmitter norepinephrine, has been the most studied, but PET neurotracers, such as (11)C-HED, are also under investigation. The ability of cardiac neuronal imaging to visualize and measure underlying molecular processes should allow it to provide a perspective on cardiac disease that other testing modalities cannot.