Jin-Chul Paeng

Noninvasive Imaging of Myocardial Inflammation in Myocarditis using 68Ga-tagged Mannosylated Human Serum Albumin Positron Emission Tomography

The diagnosis of myocarditis traditionally relies on invasive endomyocardial biopsy but none of the imaging studies so far are specific for infiltration of the inflammatory cells itself. We synthesized 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA) by conjugating human serum albumin with mannose, followed by conjugation with NOTA and labeling it with 68Ga. The efficacy of 68Ga-NOTA-MSA positron emission tomography (PET) for imaging myocardial inflammation was tested in a rat myocarditis model. A significant number of mannose receptor-positive inflammatory cells infiltrated the myocardium in both human and rat myocarditis tissue. 68Ga-NOTA-MSA uptake was upregulated in organs of macrophage accumulation, such as liver, spleen, bone marrow and myocardium (0.32 (0.31~0.33) for normal versus 1.02 (0.86~1.06) for myocarditis (median (range), SUV); n=4~6 per group, p-value=0.01). 68Ga-NOTA-MSA uptake in the left ventricle was upregulated in myocarditis compared with normal rats (2.29 (1.42~3.40) for normal versus 4.18 (3.43~6.15) for myocarditis (median (range), average standard uptake value ratio against paraspinal muscle); n=6 per group, p-value<0.01), which was downregulated in rats with cyclosporine-A treated myocarditis (3.69 (2.59~3.86) for myocarditis versus 2.28 (1.76~2.60) for cyclosporine-A treated myocarditis; n=6 per group, p-value<0.01). The specificity of the tracer was verified by administration of excess non-labeled MSA. 68Ga-NOTA-MSA uptake was significantly enhanced earlier in the evolution of myocarditis before any signs of inflammation could be seen on echocardiography. These results demonstrate the potential utility of visualizing infiltration of mannose receptor-positive macrophages with 68Ga-NOTA-MSA PET in the early diagnosis of as well as in the monitoring of treatment response of myocarditis.

Coronary computed tomography angiography vs. myocardial single photon emission computed tomography in patients with intermediate risk chest pain: a randomized clinical trial for cost-effectiveness comparison based on real-world cost

AIMS To compare the cost-effectiveness of coronary computed tomography angiography (CCTA) vs. myocardial single photon emission computed tomography (SPECT) in patients with stable intermediate risk chest pain. METHODS AND RESULTS Non-acute patients with 10-90% pre-test probability of coronary artery disease from three high-volume centres in Korea (n = 965) were randomized 1:1 to CCTA or myocardial SPECT as the initial non-invasive imaging test. Medical costs after randomization, the downstream outcome, including all-cause death, acute coronary syndrome, cerebrovascular accident, repeat revascularization, stent thrombosis, and significant bleeding following the initial test and the quality-adjusted life-years (QALYs) gained by the EuroQoL-5D questionnaire was compared between the two groups. In all, 903 patients underwent the initially randomized study (n = 460 for CCTA, 443 for SPECT). In all, 65 patients underwent invasive coronary angiography (ICA) in the CCTA and 85 in the SPECT group, of which 4 in the CCTA and 30 in the SPECT group demonstrated no stenosis on ICA [6.2% (4/65) vs. 35.3% (30/85), P-value < 0.001]. There was no difference in the downstream clinical events. QALYs gained was higher in the SPECT group (0.938 vs. 0.955, P-value = 0.039) but below the threshold of minimal clinically important difference of 0.08. Overall cost per patient was lower in the CCTA group (USD 4514 vs. 5208, P-value = 0.043), the tendency of which was non-significantly opposite in patients with 60-90% pre-test probability (USD 5807 vs. 5659, P-value = 0.845). CONCLUSION CCTA is associated with fewer subsequent ICA with no difference in downstream outcome. CCTA may be more cost-effective than SPECT in Korean patients with stable, intermediate risk chest pain.

PRACTICAL INTEGRATIVE DIAGNOSTIC STRATEGY FOR PATIENTS WITH SUSPECTED CORONARY ARTERY DISEASE: INSIGHT FROM 1,286 PATIENTS UNDERGOING BOTH ANATOMICAL AND FUNCTIONAL TESTS

methods: A total of 1,286 patients who underwent both CCTA and SPECT within 90 days, between November 2004 and November 2010, were retrospectively reviewed in 2 cardiac centers. Diagnostic performance of CCTA and SPECT were compared using invasive coronary angiography (ICA) as a reference standard. The cardiac events including cardiac death, non-fatal myocardial infarction, unstable angina and late (> 90 days after the exam) revascularization were assessed.