Biomedical subjects
Publications and source records attributed to Vasken Dilsizian.
Heart failure (HF), a heterogeneous syndrome of epidemic proportions, is increasingly defined by its underlying molecular and genomic alterations. Molecular cardiac imaging has emerged as a complementary discipline that has improved the understanding of the pathophysiologic principles governing experimental HF and has a potential to revolutionize assessment and management of HF in humans.
Long-chain free fatty acids and glucose account for the vast majority of ATP production in the heart. An alteration of fatty acid oxidation is considered to be a sensitive marker of ischemia and myocardial damage. Recently, several radiolabeled fatty acid analogs have been introduced to assess myocardial cellular function. The use of such analogs has enabled the analysis of cardiac metabolism and led to the identification of prior ischemic events, termed 'ischemic memory'. Such advances will find use in the clinical setting for the diagnosis and treatment of subclinical or progressive cardiovascular disorders, as in acute coronary syndrome, that often remain elusive with traditional imaging approaches.
Multiple strategies and testing modalities are available to evaluate patients presenting to the emergency department with cardiac complaints. Many provide anatomic and prognostic information about coronary stenosis and long-term out-comes. Although nuclear and stress echo imaging have the ability to predict outcomes in patients in the emergency department population, the newer modalities of cardiac imaging (EBCT, MDCT,and CMR) continue to show promising results and may soon be incorporated into emergency department chest pain centers. Protocols can be developed within an institution to meet the needs of the patient population while minimizing risk and improving outcomes for all patients.
PURPOSE OF REVIEW: The assessment of myocardial viability provides important information that may guide therapeutic decisions in patients with coronary artery disease and left ventricular dysfunction. This review describes methods for assessing myocardial viability using single-photon emission computed tomography, with an emphasis on how to optimize the detection of viable myocardium using current techniques. Relevant comparisons of radionuclide techniques with echocardiographic methods are also discussed. RECENT FINDINGS: The basis for the assessment of myocardial viability using radionuclides is reviewed briefly. Radionuclide techniques provide important prognostic information that may affect the decision on if patients with coronary artery disease should be revascularized or treated medically. Data suggest that dobutamine stress echocardiography may underestimate viability in certain patients. Radionuclide techniques that assess both radiotracer uptake and ventricular function can provide a comprehensive approach to detect viable myocardium in most patients. SUMMARY: The methods for assessing myocardial viability using single-photon emission computed tomography are accurate, reproducible, and widely available. Viability testing should be considered in patients with known coronary artery disease and left ventricular dysfunction. Further studies are warranted to assess the affect of viability assessment on clinical outcomes.
BACKGROUND: After myocardial ischemia, prolonged suppression of fatty acid metabolism may persist despite restoration of blood flow, which is called metabolic stunning. We hypothesized that a branched-chain fatty acid, beta-methyl-p-[(123)I]-iodophenyl-pentadecanoic acid (BMIPP), might identify the presence of myocardial ischemia late after demand ischemia at rest up to 30 hours later. METHODS AND RESULTS: In 32 patients with exercise-induced ischemia on thallium SPECT, BMIPP was injected at rest within 30 hours of ischemia. SPECT images were acquired beginning 10 minutes after injection (early) and again 30 minutes after injection (delayed). Thallium and BMIPP SPECT data were read separately by 3 observers blinded to other imaging and clinical data. Agreement between BMIPP and thallium data for the presence of an abnormality on the patient level was 91% (95% CI, 75 to 98) for the early BMIPP data and 94% (95% CI, 79 to 99) for the delayed BMIPP data. Agreement between delayed BMIPP and thallium was 95% among 21 patients studied on the same day, a mean of 6.2+/-1.4 hours after exercise-induced ischemia, and 91% among the 11 patients studied on the next calendar day, a mean of 24.9+/-2.6 hours after ischemia (P=NS). The magnitude of resting BMIPP metabolic defect by semiquantitative visual analysis was correlated to the magnitude of exercise-induced thallium perfusion defect (r=0.6, P<0.001 for early BMIPP; r=0.5, P=0.005 for delayed BMIPP). CONCLUSIONS: Metabolic imaging with BMIPP identifies patients with recent exercise-induced myocardial ischemia. These findings support the concept that BMIPP imaging can successfully demonstrate the metabolic imprint of a stress-induced ischemic episode, also known as ischemic memory.
BACKGROUND: Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device (LVAD) implantation. In addition, we sought to gain preliminary information on graft survival and any associated changes in cardiac function. METHODS AND RESULTS: Thirty patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twenty-four patients with a history of previous myocardial infarction and a left ventricular ejection fraction <40% were enrolled in the CABG arm. In a second arm, 6 patients underwent LVAD implantation as a bridge to heart transplantation, and patients donated their explanted native hearts for testing at the time of heart transplantation. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term, unexpected adverse events. Follow-up positron emission tomography scans showed new areas of glucose uptake within the infarct scar in CABG patients. Echocardiography measured an average change in left ventricular ejection fraction from 28% to 35% at 1 year and of 36% at 2 years. Histological evaluation in 4 of 6 patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. CONCLUSIONS: These results demonstrate the survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality offers a potential therapeutic treatment for end-stage heart disease.
The influence of the renin-angiotensin system (RAS) is recognized in cardiac and vascular injury. An extrinsic RAS has been known for decades, and an equally important intrinsic RAS has been discovered recently. The latter leads to pathologic tissue alterations in the absence of systemic stimuli and may be the main source of local tissue effects of RAS. A new radiotracer fluorobenzoyl-lisinopril was synthesized by radiolabeling benzoic acid active ester with 18F and reacting that with the epsilon-amino group of lisinopril. The presence of angiotensin-converting enzyme (ACE) activity and angiotensin II receptors was examined in relation to myocardial fibrosis. This tissue-specific radioligand represents the first study of ACE in the human heart. This article presents preliminary data on imaging the RAS in the human cardiac tissue and discusses the potential for clinical application of these imaging techniques to human patients.
Recent advances in positron emission tomography (PET) instrumentation have paralleled those of multichannel computed tomography (CT) for cardiac applications. Whereas multichannel CT angiography provides information on the presence and extent of anatomical luminal narrowing of epicardial coronary arteries, stress myocardial perfusion PET provides information on the downstream functional consequences of such anatomic lesions. With the advent of hybrid PET/CT systems, such complementary information of anatomy and physiology can be realized immediately at the same imaging session. By acquiring dynamic, gated myocardial perfusion data, PET studies provide insight into impairment of regional coronary blood flow reserve and microvascular endothelial dysfunction. This paper presents recent developments in PET detector materials, acquisition modes, combined PET/CT scanners, rubidium-82 (Rb-82) gated myocardial perfusion studies and analysis methods for absolute myocardial blood flow quantification.
BACKGROUND: Dipyridamole and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects. METHODS AND RESULTS: In a multicenter, randomized, single-blind, 2-arm crossover trial, 240 patients underwent 2 single photon emission computed tomographic (SPECT) imaging studies in random order, first after pharmacological stress with adenosine and a second study with the selective adenosine A2A receptor agonist binodenoson, using 1 of 4 dosing regimens. Safety, tolerability, and SPECT image concordance between the 2 agents were examined. Exact categorical agreement in the extent and severity of reversible perfusion defects ranged from 79% to 87%, with kappa values from 0.69 to 0.85, indicating very good to excellent agreement between binodenoson and adenosine. The risk of any safety event/side effect was significantly lower with any dose of binodenoson than with adenosine (P< or =0.01) because of a dose-related reduction in subjective side effects, as objective events were infrequent. There was a reduction in the severity of chest pain, dyspnea, and flushing in all binodenoson doses compared with adenosine (P<0.01), and the magnitude of severity reduction was dose-related. CONCLUSIONS: The selective adenosine A2A receptor agonist binodenoson results in an extent and severity of reversible perfusion defects on SPECT imaging similar to nonselective adenosine receptor stimulation, accompanied by a dose-related reduction in the incidence and severity of side effects.
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