Vasken Dilsizian

Effect of metoprolol on absolute myocardial blood flow in patients with heart failure secondary to ischemic or nonischemic cardiomyopathy

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Strategies for defining an optimal risk-benefit ratio for stress myocardial perfusion SPECT.

Tremendous growth in medical imaging has prompted a re-focusing on the appropriateness of testing and the rationale for exposure to ionizing radiation for large segments of the adult population at intermediate to high likelihood for coronary artery disease (CAD). Part I of this series addressed the technical or methodological approaches to measuring radiation exposure and laboratory approaches to reducing exposure including the clinical utility of stress only imaging. In the current statement, we present a clinical approach for defining the risk:benefit ratio of myocardial perfusion imaging (MPI) focusing on the appropriate use of single photonemission computed tomography (SPECT) or positron emission tomography (PET) MPI. We also review the concept of ‘‘patient-centered imaging’’ and discuss methods for effectively addressing patient concerns regarding procedural risk.

Variation of Heart-to-Mediastinal Ratio in 123I-mIBG Cardiac Sympathetic Imaging: Its Affecting Factors and Potential Corrections

Studies have repeatedly shown the utility of 123I-mIBG cardiac sympathetic imaging for identifying symptomatic heart failure patients most likely to experience adverse cardiac events. Delayed heart-to-mediastinal ratio (H/M) and washout rate derived from meta-iodobenzylguanidine (mIBG) scintigraphy have been used to monitor response to medical treatment. However, there is great variation of H/M ratio among publications from various institutions. The current article systemically reviews factors that can potentially affect H/M ratio, particularly the acquisition parameters, and proposes new approaches and/or procedures to standardize the imaging procedure and minimize the variation of H/M among institutions.

18F-Fluorodeoxyglucose PET Imaging of Coronary Atherosclerosis and Plaque Inflammation

The emphasis of current cardiovascular imaging modalities is on the anatomic detection of coronary artery luminal narrowing. However, in the clinical setting, vulnerable plaques that are not flow limiting may account for the majority of cardiovascular events. Thus, the pursuit for developing noninvasive imaging techniques that target vulnerable plaques is a laudable goal. Recent studies have demonstrated the clinical feasibility of direct visualization and characterization of coronary and carotid artery plaques with 18F-fluorodeoxyglucose (FDG) positron emission tomography imaging. In experimental studies, the intensity of FDG uptake has been shown to correlate with macrophage density and inflammatory state of plaques. Vascular plaque FDG uptake has been linked to cardiovascular events such as myocardial infarction and stroke. Anti-inflammatory drugs and statins have been shown to attenuate FDG uptake in plaques. Thus, the identification of FDG uptake in vascular plaques may have important clinical implications for predicting and preventing future cardiovascular events.

The role and regulation of cardiac angiotensin-converting enzyme for noninvasive molecular imaging in heart failure

Congestive heart failure is a pathologic condition characterized by progressive decrease in left ventricular contractility and consequent decline of cardiac output. There is convincing clinical and experimental evidence that the renin-angiotensin system (RAS) and its primary effector peptide, angiotensin II, are linked to the pathophysiology of interstitial fibrosis, cardiac remodeling, and heart failure. In addition to the traditional endocrine or circulating RAS, an active tissue RAS has been characterized. Tissue angiotensin-converting enzyme and locally synthesized angiotensin II, for example, by chymase, exert local trophic effects that modulate gene expression, which regulates growth and proliferation in both myocytes and nonmyocytes. The existence of the tissue RAS offers an opportunity for targeted imaging, which may be of considerable value for guiding medical therapy.

The Potential Role of Iodine-123 Metaiodobenzylguanidine Imaging for Identifying Sustained Ventricular Tachycardia in Patients with Cardiomyopathy

Implantable cardioverter-defibrillators (ICDs) significantly reduce mortality in patients with depressed left ventricular ejection fraction (LVEF) and heart failure (HF). However, shortcomings of LVEF to accurately identify those at greatest risk of ventricular tachyarrhythmias have led to the pursuit of alternative means to refine qualification criteria for ICD implantation. It is well established that imaging the cardiac nervous system with123I meta-iodobenzylguanidine (123I-mIBG) provides incremental prognostic value in patients with HF beyond LVEF. Whether 123I-mIBG will also play an important role for identifying and/or predicting sustained ventricular tachyarrhythmias in patients with cardiomyopathy and determining those who may benefit from ICD implantation is currently under investigation. Novel imaging approaches that pinpoint the site of ventricular arrhythmias and guide ventricular tachycardia ablation are presented.

Targeted Metabolic Imaging to Improve the Management of Heart Disease

Tracer techniques are powerful methods for assessing rates of biological processes in vivo. A case in point is intermediary metabolism of energy providing substrates, a central feature of every living cell. In the heart, the tight coupling between metabolism and contractile function offers an opportunity for the simultaneous assessment of cardiac performance at different levels in vivo: coronary flow, myocardial perfusion, oxygen delivery, metabolism, and contraction. Noninvasive imaging techniques used to identify the metabolic footprints of either normal or perturbed cardiac function are discussed.

Introduction of New Tests: Low Are the Mountains, High the Expectations

There has been a significant movement recently in a rather stagnant field of cardiovascular radionuclide imaging in the U.S. Two relatively large prospective clinical studies have just been completed with 123I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid and 123I-labeled meta -

Delayed recovery of fatty acid metabolism after transient myocardial ischemia: A potential imaging target for “ischemic memory”

The myocardium preferentially oxidizes free fatty acids for energy production. However, the dependency of this metabolic pathway on oxygen makes this process vulnerable to ischemia. The energy requirements of the myocardium are subsequently met by the oxidation of carbohydrates, particularly glucose. Recovery of fatty acid metabolism lags behind restoration of perfusion, resulting in the phenomenon ofmetabolic stunning. This decrease of fatty acid utilization following ischemia can be imaged with fatty acid radiotracers, particularly β-Methyl-p-123I-iodophenyl pentadecanoic acid (BMIPP), which demonstrates markedly limited metabolism via β-oxidation, resulting in prolonged retention in the cardiomyocyte. Thus, in patients presenting with chest pain and no prior myocardial infarction, abnormal BMIPP uptake at rest reflects metabolic alteration caused by the preceding ischemia, also termedischemic memory.

Microvascular Angina: Assessment of Coronary Blood Flow, Flow Reserve, and Metabolism

Microvascular angina (MVA) is an often overlooked cause of significant chest pain. Decreased myocardial perfusion secondary to dysregulated blood flow in the microvasculature can occur in the presence or absence of obstructive epicardial coronary artery disease. The corresponding myocardial ischemia and angina is now a well-established diagnosis, made by detection of decreased coronary flow reserve (CFR). Although low CFR and MVA are associated with poor prognosis, there is initial evidence for reversibility of this abnormal vascular regulation with aggressive medical therapy and control of associated risk factors. Current assessment of MVA is carried out predominantly during cardiac catheterization; however, noninvasive techniques to assess CFR are being developed, including PET, MRI, and CT modalities. Quantitative tracer techniques or imaging of metabolic disturbances reflecting ischemia will likely enhance diagnostic approaches for such patients as well as allow more frequent monitoring of response to therapy.