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Biomedical subjects

George A Beller

Publications and source records attributed to George A Beller.

At least 19 recordsLinked to original sources

A proposal for an advanced cardiovascular imaging training track.

Cardiovascular (CV) imaging has experienced major growth and technological advances with respect to the long-standing traditional cardiac imaging procedures of echocardiography and nuclear cardiology, the emergence of cardiac computed tomography and magnetic resonance imaging in clinical practice, and multimodality and molecular imaging as new technologies. Therefore, it is perhaps timely to change the training paradigm for fellows interested in emphasizing CV imaging as a subspecialty in their professional careers and desiring extensive training in all CV imaging modalities. Proposed is the establishment of a formal fourth year of training leading to board certification in advanced CV imaging. Areas of training would include the acquisition of knowledge of physics and instrumentation related to the various imaging modalities, interpretation and quantitation of imaging variables, multimodality imaging technology, molecular and vascular imaging, and clinical guidelines with appropriateness criteria for all technologies. The training track would lead to an American Board of Internal Medicine examination for a Certificate of Added Qualification, similar to that for subspecialization in electrophysiology and interventional cardiology, with noninvasive cardiologists who have already completed fellowship training given the opportunity to sit for an examination on the basis of predetermined eligibility criteria. One benefit of this CV imaging subspecialty track that provides cardiologists with expertise in all imaging modalities is the capability to select the best modality for the clinical indication and to independently interpret multimodality imaging studies. Its rigorous didactic and procedural requirements would enhance quality of CV imaging, enhance research, and increase the speed with which new discoveries are translated into practice. This ultimately would yield better patient outcomes.

Cardiology↗

Fractional flow reserve of infarct-related arteries identifies reversible defects on noninvasive myocardial perfusion imaging early after myocardial infarction.

OBJECTIVES: We hypothesized that fractional flow reserve (FFR) of an infarct-related artery (IRA) early after myocardial infarction (MI) identifies inducible ischemia on noninvasive imaging. BACKGROUND: Early after MI, IRAs frequently have angiographically indeterminant lesions. Whether FFR can detect reversible perfusion defects early after MI when dynamic microvascular abnormalities are present is not known. METHODS: Rest and dipyridamole (DP)-stress 99mTc sestamibi single-photon emission computed tomography (SPECT) were performed in 48 patients 3.7 +/- 1.3 days after MI, with 23 patients undergoing concurrent myocardial contrast echocardiography (MCE). Angiography, FFR, and percutaneous coronary intervention (PCI) of the IRA (as necessary) were subsequently performed. Follow-up SPECT was performed 11 weeks after PCI to identify true reversibility on baseline SPECT. RESULTS: The sensitivity, specificity, positive and negative predictive value, and concordance of FFR < or =0.75 for detecting reversibility on SPECT were 88%, 50%, 68%, 89%, and 71% (chi-square <0.001), respectively; which improved to 88%, 93%, 88%, 93%, and 91% (chi-square <0.001), respectively, for the detection of true reversibility. The corresponding values of FFR < or =0.75 for detecting reversibility on DP-MCE were 90%, 100%, 100%, 75%, and 93% (chi-square <0.001), respectively, and on either SPECT or MCE were 88%, 93%, 91%, 91%, and 91% (chi-square <0.001), respectively. The optimal FFR value for discriminating inducible ischemia on noninvasive imaging was 0.78. CONCLUSIONS: Fractional flow reserve of the IRA accurately identifies reversibility on noninvasive imaging early after MI. These findings support the utility of FFR early after MI.

Aged↗

Organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of coronary stenoses.

BACKGROUND: Technetium 99m N-DBODC5 is a new myocardial perfusion tracer shown to exhibit high heart uptake and rapid liver clearance in normal rats. The objectives of this canine study were (1) to compare the organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 with Tc-99m sestamibi over a period of 3 hours in a more clinically relevant large animal species and (2) to compare the myocardial uptake of Tc-99m N-DBODC5 with thallium 201 when co-injected during vasodilator stress in dogs with coronary stenoses. METHODS AND RESULTS: At peak adenosine-induced hyperemia, 10 dogs with critical left anterior descending artery stenoses received either Tc-99m N-DBODC5 (n = 6) or Tc-99m sestamibi (n = 4) and microspheres, followed by serial imaging and blood sampling over a period of 3 hours. Another 14 dogs with either critical (n = 7) or mild (n = 7) left anterior descending artery stenoses underwent simultaneous injection of Tc-99m N-DBODC5, Tl-201, and microspheres during peak vasodilator stress. Like sestamibi, Tc-99m N-DBODC5 showed good myocardial uptake with slow washout and minimal redistribution over a period of 3 hours (P = not significant); however, Tc-99m N-DBODC5 cleared more rapidly from the liver (heart-lung ratio at 30 minutes, 0.92+/-0.11 versus 0.51 +/- 0.05; P < .05). When injected during hyperemic flow, the myocardial extraction plateau for Tc-99m N-DBODC5 was lower than that for Tl-201 and was intermediate between Tc-99m sestamibi and Tc-99m tetrofosmin. CONCLUSIONS: Excellent organ biodistribution and myocardial uptake and clearance kinetic properties, combined with rapid liver clearance and a favorable flow-extraction relationship, make Tc-99m N-DBODC5 a very promising new myocardial perfusion imaging agent.

Adenosine↗

Prognostic role of single-photon emission computed tomography (SPECT) imaging in myocardial viability.

PURPOSE OF REVIEW: Cardiac imaging is evolving rapidly. Appropriate use of this technology could reduce morbidity and mortality, but inappropriate use could have a significant financial burden. Single-photon emission computed tomography imaging is widely available. This review summarizes the clinical utility and limitations of the prognostic role of single-photon emission computed tomography imaging for myocardial viability in patients with coronary artery disease and left-ventricular dysfunction. RECENT FINDINGS: 201Tl single-photon emission computed tomography, 99mTc single-photon emission computed tomography with sestamibi or tetrofosmin, and 18F-fluorodeoxyglucose single-photon emission computed tomography are validated tools for assessing myocardial viability. These techniques have a very similar predictive value in determining regional and global response to revascularization. 201Tl single-photon emission computed tomography viability studies are predictive of reverse left-ventricular remodeling, symptom improvement, and patient outcome after revascularization. Combination imaging with dual-isotope simultaneous acquisition single-photon emission computed tomography or positron-emission tomography/single-photon emission computed tomography may improve the positive and negative predictive values of single-photon emission computed tomography-based viability studies. SUMMARY: Single-photon emission computed tomography-based myocardial viability testing is an important diagnostic modality due to widespread availability and reasonably good sensitivity and specificity for detecting viable myocardium and predicting clinical and functional responses to revascularization. In the future single-photon emission computed tomography viability techniques may have a prognostic role in predicting responses to cardiac resynchronization therapy and evaluating myocardial stem-cell transplantation.

Coronary Artery Disease↗

Reduction of infarct size and postischemic inflammation from ATL-146e, a highly selective adenosine A2A receptor agonist, in reperfused canine myocardium.

Adenosine and adenosine A(2A) receptor agonists have been shown to limit myocardial infarct size when given at vasodilatory doses during reperfusion. This beneficial effect is thought to be due, in part, to stimulation of adenosine A(2A) receptors on inflammatory cells. The specific aims of this study were to determine whether the anti-inflammatory and cardioprotective properties of a novel adenosine A(2A) receptor agonist, ATL-146e (ATL), alone or in combination with the phosphodiesterase IV inhibitor rolipram would occur using very low, nonvasodilating doses. In a canine model of reperfused myocardial infarction, low-dose ATL given alone reduced infarct size by 45% (P < 0.05 vs. control). When ATL was combined with a very low dose of rolipram (0.001 microg.kg(-1).min(-1)), a marked reduction in P-selectin expression and neutrophil infiltration (51% lower; P < 0.001 vs. control) was seen and the infarct size reduction (58% lower; P < 0.01 vs. control) was greater than observed with ATL (45% lower; P < 0.05) or rolipram (33% lower; P < 0.05) alone. In conclusion, a low, nonvasodilating dose of ATL, a highly selective adenosine A(2A) receptor agonist, reduced infarct size after reperfusion. Furthermore, combining ATL and the phosphodiesterase IV inhibitor rolipram reduced infarct size even more than either agent alone. Such combination therapy may be beneficial clinically by potentiating cardioprotection after coronary reperfusion at doses far below those producing vasodilatation or side effects.

3',5'-Cyclic-AMP Phosphodiesterases↗

Electromechanical mapping identifies improvement in function and retention of contractile reserve after revascularization in ischemic cardiomyopathy.

BACKGROUND: We hypothesized that (1) a significant proportion of ischemic dysfunctional segments that do not improve function will demonstrate postrevascularization contractile reserve and (2) electromechanical mapping (EMM) can identify segments that improve function as well as those with postrevascularization contractile reserve, a potential indicator of delayed functional improvement. METHODS AND RESULTS: Eighteen patients with severe ischemic left ventricular dysfunction underwent EMM and dobutamine (D) cardiac magnetic resonance imaging (CMR) followed by revascularization. Four months after revascularization, all patients underwent a repeated D-CMR, and at 35 months, a subgroup (n=6) underwent a third CMR. Of 120 dysfunctional segments, 60 segments had improved rest function (IRF) and 60 did not. Twenty-eight of 60 segments (47%) that did not improve RF demonstrated postrevascularization contractile reserve (CR), and 32 of 60 segments (53%) that demonstrated neither IRF nor CR were persistently dysfunctional (PD). CR segments recovered significantly greater late function compared with IRF or PD: 14+/-12% vs 2+/-5% and 4+/-7%, respectively; P<0.05. EMM ratio, defined as the unipolar voltage divided by linear shortening, was significantly higher in IRF segments compared with segments that did not improve RF: 2.4+/-4.5 vs 0.7+/-3.5, P<0.05. Unipolar voltage was stepwise lower in normal, IRF, CR, and PD segments (10.5+/-4.7, 9.3+/-3.9, 8.8+/-3.2, and 7.4+/-2.3 mV, respectively; P<0.01 for trend). CONCLUSIONS: Almost half of dysfunctional myocardial segments in chronic ischemic heart disease that do not improve RF early after revascularization demonstrate early CR and delayed functional recovery. EMM parameters can identify segments that improve RF and retain CR early after revascularization.

Adult↗

Comparison of the predictive value of exercise-induced ST depression versus exercise technetium-99m sestamibi single-photon emission computed tomographic imaging for detection of coronary artery disease in patients with left ventricular hypertrophy.

Scant knowledge exists regarding the significance of either additional ST depression in the presence of baseline depression or new stress-induced ST depression in patients with left ventricular (LV) hypertrophy. Accordingly, the purpose of this investigation is to determine whether the appearance and/or severity of ST abnormalities during exercise stress testing can accurately predict the prevalence of ischemic burden as measured by quantitative technetium-99m-sestamibi single-photon emission computed tomographic imaging in patients with LV hypertrophy. The results show that the presence of exercise ST-segment depression, as well as its magnitude, are not accurate predictors for identifying patients with coronary artery disease in the presence of electrocardiographic criteria for LV hypertrophy.

Adult↗

99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearance: comparison with 99mTc-sestamibi and 99mTc-tetrofosmin in rats.

UNLABELLED: (99m)Tc-[bis (dimethoxypropylphosphinoethyl)-ethoxyethylamine (PNP5)]-[bis (N-ethoxyethyl)-dithiocarbamato (DBODC)] nitride (N-PNP5-DBODC or N-DBODC5) is a new monocationic myocardial perfusion tracer. We sought to compare the myocardial uptake and clearance kinetics and organ biodistribution of (99m)Tc-N-DBODC5 with (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. METHODS: Seventy-five anesthetized Sprague-Dawley rats were injected intravenously with 22.2-29.6 MBq (99m)Tc-N-DBODC5 (n = 25), (99m)Tc-sestamibi (n = 25), or (99m)Tc-tetrofosmin (n = 25). Rats were euthanized at either 2, 10, 20, 30, or 60 min after injection and gamma-well counting was performed on excised organ (heart, lung, and liver) and blood samples. In 3 additional rats, serial in vivo whole-body gamma-camera imaging with each tracer was performed. RESULTS: (99m)Tc-N-DBODC5 cleared rapidly from the blood pool. At 2 min after injection, (99m)Tc-N-DBODC5 blood activity was significantly lower than either (99m)Tc-sestamibi or (99m)Tc-tetrofosmin (P < 0.01) and remained lower over 60 min. Myocardial (99m)Tc-N-DBODC5 uptake was rapid (2.9% +/- 0.1% injected dose/g at 2 min), and there was no significant clearance over 60 min, similar to (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. All 3 tracers exhibited rapid lung clearance. Importantly, (99m)Tc-N-DBODC5 cleared more rapidly from the liver than either (99m)Tc-sestamibi or (99m)Tc-tetrofosmin. As early as 30 min after injection, (99m)Tc-N-DBODC5 heart-to-liver ratio was 5.7 +/- 1.0 versus 1.6 +/- 0.1 and 2.9 +/- 0.3 for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin (P < 0.05). By 60 min, (99m)Tc-N-DBODC5 heart-to-liver ratio further increased to 18.4 +/- 2.0 compared with 2.6 +/- 0.2 and 5.8 +/- 0.7 for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin (P < 0.001). The rapid blood pool, lung, and liver clearance of (99m)Tc-N-DBODC5 resulted in excellent-quality myocardial images within 30 min after injection. CONCLUSION: (99m)Tc-N-DBODC5 is a promising new myocardial perfusion tracer with superior biodistribution properties. The rapid (99m)Tc-N-DBODC5 liver clearance may shorten the duration of imaging protocols by allowing earlier image acquisition and may markedly reduce the problem of photon scatter from the liver into the inferoapical wall on myocardial images.

Animals↗