Thomas H. Schindler

Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.

Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments

Despite major advances in mechanical and pharmacological reperfusion strategies to improve acute myocardial infarction (MI) injury, substantial mortality, morbidity, and socioeconomic burden still exists. To further reduce infarct size and thus ameliorate clinical outcome, the focus has also shifted towards early detection of MI with high-sensitive troponin assays, imaging, cardioprotection against pathophysiological targets of myocardial reperfusion injury with mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hypoxemia) and newer pharmacological interventions (atrial natriuretic peptide, cyclosporine A, and exenatide). Evidence from animal models of myocardial ischaemia and reperfusion also demonstrated promising results on more selective anti-inflammatory compounds that require additional validation in humans. Cardiac stem cell treatment also hold promise to reduce infarct size and negative remodelling of the left ventricle that may further improves symptoms and prognosis in these patients. This review focuses on the pathophysiology, detection, and reperfusion strategies of ST-segment elevation MI as well as current and future challenges to reduce ischaemia/reperfusion injury and infarct size that may result in a further improved outcome in these patients.

Advances in Cardiac SPECT and PET Imaging: Overcoming the Challenges to Reduce Radiation Exposure and Improve Accuracy

Nuclear cardiology came of age in the 1970s and subsequently has expanded so that more than 9 million single-photon emission computed tomography (SPECT) studies are performed annually in North America. Coronary artery disease management has demanded a reliable technique that will detect, risk stratify, and assist with revascularization decisions. Using cardiac SPECT and positron-emission tomography (PET), researchers and clinicians have sought to achieve excellence in coronary artery disease diagnosis and risk stratification, and strive to achieve higher standards in these areas. Developments in other cardiac imaging modalities, however, such as cardiac computed tomography, cardiac magnetic resonance, and echocardiography, have raised expectations in terms of diagnostic accuracy and achieving high quality images with little or no ionizing radiation exposure. The challenge facing nuclear cardiology as it embarks upon a fifth decade of clinical use is whether high quality images can be obtained at lower radiation exposures. In this review we consider current practice in SPECT and PET perfusion imaging. We discuss emerging advances in techniques, technologies, and radiotracers that focus specifically on improvements in image quality that enhance diagnostic accuracy while reducing radiation exposure. We provide a perspective as to the future roles of cardiac SPECT and PET in ischemic heart disease, and consider emerging novel applications beyond perfusion imaging. Although for a number of years nuclear cardiology has shone brightly as a leading light for the imaging of ischemic heart disease, its half-life has not yet been reached. Instead, even with the pressure to reduce radiation exposure, the future continues to look bright for cardiac SPECT and PET.

New SPECT and PET radiopharmaceuticals for imaging cardiovascular disease

Nuclear cardiology has experienced exponential growth within the past four decades with converging capacity to diagnose and influence management of a variety of cardiovascular diseases. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m radiotracers or thallium-201 has dominated the field; however new hardware and software designs that optimize image quality with reduced radiation exposure are fuelling a resurgence of interest at the preclinical and clinical levels to expand beyond MPI. Other imaging modalities including positron emission tomography (PET) and magnetic resonance imaging (MRI) continue to emerge as powerful players with an expanded capacity to diagnose a variety of cardiac conditions. At the forefront of this resurgence is the development of novel target vectors based on an enhanced understanding of the underlying pathophysiological process in the subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered to target a specific subcellular process has the capacity to improve diagnostic accuracy and deliver enhanced prognostic information to alter management. This paper, while not comprehensive, will review the recent advancements in radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis, atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry and preclinical and clinical development in addition to molecular imaging with emerging modalities such as cardiac MRI and PET-MR will be discussed.

Cardiovascular nuclear imaging: Balancing proven clinical value and potential radiation risk

The debate on the potential risk of radiation exposure from diagnostic imaging tests highlights the importance of balancing the demonstrated clinical benefit and the theoretic risk of cardiovascular imaging studies. The Cardiovascular Council of the Society of Nuclear Medicine upholds the responsible application of imaging studies that use radiotracers associated with relatively small amounts of ionizing radiation. Radionuclide-based cardiac imaging studies, including myocardial perfusion imaging (MPI), provide accurate diagnostic and prognostic information about patients with suspected or known heart disease. There is a large body of scientific evidence on the clinical value of MPI, based on studies performed on many thousands of patients. On the basis of this information, appropriate-use criteria and guidelines were developed and endorsed by the Society of Nuclear Medicine and other professional societies, including the American College of Cardiology, American Heart Association, and American Society of Nuclear Cardiology (1). Cardiovascular nuclear medicine studies provide highly sensitive and specific tests that may be indicated for the evaluation of diagnosis, prognosis, and treatment response of coronary artery disease, as well as for selection of patients who benefit from revascularization. The value and justification of MPI for risk assessment is based on large observational outcome studies that demonstrate accurate risk stratification with radionuclide-based MPI in populations with an intermediate pretest risk. The incremental prognostic value of SPECT MPI is greater than that of the exercise electrocardiography stress test or coronary angiography. The cost effectiveness of MPI as a gatekeeper to coronary angiography has been established after being carefully and extensively studied. Several recent publications have raised concern about the potential harmful effects of ionizing radiation associated with cardiac imaging. Review of the measurement of radiation and associated biologic effects can help put this issue into reasonable perspective. Radiation effective dose is a measure used to estimate the biologic effects of radiation. Measuring the radiation effective dose associated with diagnostic imaging is complex and imprecise and often results in varying estimates among experts (2). A typical effective dose for a rest–stress same-day SPECT scan using 99mTclabeled agents (1,110 MBq [30 mCi] stress, 370 MBq [10 mCi] rest), the most commonly used MPI protocol, is approximately 10 mSv. Other agents and protocols are associated with a wide range of radiation exposure (2). In comparison, exposure to radiation from natural sources amounts to approximately 3 mSv annually. The risk of a fatal malignancy from medical imaging–related radiation is difficult to estimate precisely but is likely small and difficult to discern from the background risk of natural malignancies. The theoretic lifetime attributable risk of cancer from a rest and stress 99mTc-based MPI study for individuals age 35 y or older is less than 1.5 in 1,000 (3). This risk is less in older patients, who constitute most patients evaluated for coronary artery disease. The estimated risk of fatal malignancy from a typical MPI study is 0.5 per 1,000 individuals, compared with a risk of death from natural cancer of 212 per 1,000 (4). The potential risk of cancer must be balanced against the risk of death, myocardial infarction, or other morbid vascular events in an appropriately referred population. This risk ranges from 1% to 10% or more per year and is orders of magnitude greater than the potential lifetime risk of cancer and death from cancer attributable to cardiovascular nuclear medicine studies. Assessment of risk-to-benefit ratio mandates a good understanding of the clinical characteristics of the patient, including risk factors for coronary artery disease, prior history of coronary artery disease, and left ventricular function. For example, given the substantially higher risk of morbid coronary events or heart failure in patients with left ventricular dysfunction, higher radiation exposure associated with 201Tl or 18F-FDG for radionuclide assessment of viability is readily justifiable. In this context, one must not fail to take into account the risks of missing important diagnostic information by not performing a test (which could potentially influence near-term management and outcomes) because of a theoretic concern about a long-term small risk of malignancy. Similarly, assessment of the significance of radiation exposure risk in population-based studies would be challenging without information on the overall pool from which the patients are selected and how representative they are of the total patient population. While the potential long-term radiation risk associated with cardiovascular nuclear medicine studies is debated (5), Received Mar. 17, 2011; revision accepted Mar. 24, 2011. For correspondence or reprints contact: Mehran M. Sadeghi, Yale University School of Medicine, 950 Campbell Ave., West Haven, CT 06516. E-mail: mehran.sadeghi@yale.edu COPYRIGHT a 2011 by the Society of Nuclear Medicine, Inc. DOI: 10.2967/jnumed.111.090654

Joint SNMMI-ASNC expert consensus document on the role of 18F-FDG PET/CT in carDiac sarcoid detection and therapy monitoring writing group

1Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota; 2Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Canada; 3Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland; 4Division of Nuclear Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; 5Section of Cardiovascular Medicine, Yale University, New Haven, Connecticut; 6Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan; 7School of Medicine, Johns Hopkins University, Baltimore, Maryland; 8Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, Florida; 9Division of Cardiology, University of Chicago Medicine, Chicago, Illinois; 10Division of Pulmonary Medicine, University of Michigan, Ann Arbor, Michigan; 11Department of Radiology and Nuclear Medicine, Duke University, Durham, North Carolina; and 12Department of Radiology, Mallinckrodt Institute of Radiology, St. Louis, Missouri

Role of risk stratification by SPECT, PET, and hybrid imaging in guiding management of stable patients with ischaemic heart disease: Expert panel of the EANM cardiovascular committee and EACVI

Risk stratification has become increasingly important in the management of patients with suspected or known ischaemic heart disease (IHD). Recent guidelines recommend that these patients have their care driven by risk assessment. The purpose of this position statement is to summarize current evidence on the value of cardiac single-photon emission computed tomography, positron emission tomography, and hybrid imaging in risk stratifying asymptomatic or symptomatic patients with suspected IHD, patients with stable disease, patients after coronary revascularization, heart failure patients, and specific patient population. In addition, this position statement evaluates the impact of imaging results on clinical decision-making and thereby its role in patient management. The document represents the opinion of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee and of the European Association of Cardiovascular Imaging (EACVI) and intends to stimulate future research in this field.

Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly

Dysregulation of the endogenous lipid mediators endocannabinoids and their G-protein-coupled cannabinoid receptors 1 and 2 (CB1R and CB2R) has been implicated in a variety of cardiovascular pathologies. Activation of CB1R facilitates the development of cardiometabolic disease, whereas activation of CB2R (expressed primarily in immune cells) exerts anti-inflammatory effects. The psychoactive constituent of marijuana, Δ9-tetrahydrocannabinol (THC), is an agonist of both CB1R and CB2R, and exerts its psychoactive and adverse cardiovascular effects through the activation of CB1R in the central nervous and cardiovascular systems. The past decade has seen a nearly tenfold increase in the THC content of marijuana as well as the increased availability of highly potent synthetic cannabinoids for recreational use. These changes have been accompanied by the emergence of serious adverse cardiovascular events, including myocardial infarction, cardiomyopathy, arrhythmias, stroke, and cardiac arrest. In this Review, we summarize the role of the endocannabinoid system in cardiovascular disease, and critically discuss the cardiovascular consequences of marijuana and synthetic cannabinoid use. With the legalization of marijuana for medicinal purposes and/or recreational use in many countries, physicians should be alert to the possibility that the use of marijuana or its potent synthetic analogues might be the underlying cause of severe cardiovascular events and pathologies.

Joint SNMMI–ASNC expert consensus document on the role of 18F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring

Joint SNMMI–ASNC expert consensus document on the role of F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring Panithaya Chareonthaitawee, Rob S. Beanlands, Wengen Chen, Sharmila Dorbala, Edward J. Miller, Venkatesh L. Murthy, David H. Birnie, Edward S. Chen, Leslie T. Cooper, Roderick H. Tung, Eric S. White, Salvador Borges-Neto, Marcelo F. Di Carli, Robert J. Gropler, Terrence D. Ruddy, Thomas H. Schindler, and Ron Blankstein

Impact of Obesity and Bariatric Surgery on Metabolism and Coronary Circulatory Function

Increases in intra-abdominal visceral adipose tissue have been widely appreciated as a risk factor for metabolic disorders such as dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, whereas this is not the case for peripheral or subcutaneous obesity. While the underlying mechanisms that contribute to these differences in adipose tissue activity remain uncertain, increases in visceral fat commonly induce metabolic dysregulation, in part because of increased venous effluent of fatty acids and/or adipokines/cytokines to the liver. Increased body weight, paralleled by an increase in plasma markers of the insulin-resistance syndrome and chronic inflammation, is independently associated with coronary circulatory dysfunction. Recent data suggest that plasma proteins originating from the adipose tissue, such as endocannabinoids (EC), leptin, and adiponectin (termed adipocytes) play a central role in the regulation and control of coronary circulatory function in obesity. Positron emission tomography (PET) in concert with tracer kinetic modeling is a well established technique for quantifying regional myocardial blood flow at rest and in response to various forms of vasomotor stress. Myocardial flow reserve assessed by PET provides a noninvasive surrogate of coronary circulatory function. PET also enables the monitoring and characterization of coronary circulatory function in response to gastric bypass-induced weight loss in initially morbidly obese individuals, to medication and/or behavioral interventions related to weight, diet, and physical activity. Whether the observed improvement in coronary circulatory dysfunction via weight loss may translate to diminution in cardiovascular events awaits clinical confirmation.