Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE) data: type 2 diabetes mellitus (DM), hypertension (HT), and coronary artery disease (CAD). We showed that epistatic single-nucleotide polymorphisms (SNPs) were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012), which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE). Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.
We evaluated the results of sequential SPECT dual-isotope imaging with Tl-201 and Tc-99m MIBI in 24 patients. all of whom also had coronary angiography within the past one month. Coronary angiography showed that 12 patients had no CAD, 4 patients had one-vessel CAD, 7 patients had two-vessel CAD and 1 patient had three-vessel CAD. Serial studies of resting Tl-201 and dipyridamole stress Tc-99m MIBI were completed within 2 hours. When more than 50% of coronary artery narrowing was considered significant, the overall sensitivity and specificity of CAD detection were 91.7%. The sensitivity of CAD detection in patients with one-vessel and multi-vessel diseases was 75% and 100%. respectively. Therefore, sequential dual-isotope SPECT demonstrated high sensitivity and specificity for CAD detection. In conclusion, sequential dual-isotope imaging is feasible and can be completed in a short time and may therefore enhance laboratory throughput and patient convenience.
Purpose: Soft tissue attenuation and scattering are major methodological limitations of myocardial perfusion SPECT. To overcome these limitations, algorithms for attenuation, scatter correction and resolution recovery (ASCRR) is being developed, while quantitative myocardial SPECT has also become available. In this study, we investigated the efficacy of an ASCRR-corrected quantitative myocardial SPECT method for the diagnosis of coronary artery disease (CAD). Materials and Methods: Seventy-five patients (M:F=51:24, $61.0{\pm}8.9$ years old) suspected of CAD who underwent coronary angiography (CAG) within $7{\pm}12$ days of SPECT(Group-I) and 20 subjects (M:F=10:10, age $40.6{\pm}9.4$) with a low likelihood of coronary artery disease (Group-II) were enrolled. Tl-201 rest/ dipyridamole-stress Tc-99m-MIBI gated myocardial SPECT was performed. ASCRR correction was peformed using a Gd-153 line source and automatic software (Vantage-Pro; ADAC Labs, USA). Using a 20-segment model, segmental perfusion was automatically quantified on both the ASCRR-corrected and uncorrected images using an automatic quantifying software (AutoQUANT; ADAC Labs.). Using these quantified values, CAD was diagnosed in each of the 3 coronary arterial territories. The diagnostic performance of ASCRR-corrected SPECT was compared with that of non-corrected SPECT. Results: Among the 75 patients of Group-I, 9 patients had normal CAG while the remaining 66 patients had 155 arterial lesions; 61 left anterior descending (LAD), 48 left circumflex (LCX) and 46 right coronary (RCA) arterial lesions. For the LAD and LCX lesions, there was no significant difference in diagnostic performance. In Group-II patients, the overall normalcy rate improved but this improvement was not statistically significant (p=0.07). However, for RCA lesions, specificity improved significantly but sensitivity worsened significantly with ASCRR correction (both p<0.05). Overall accuracy was the same. Conclusion: The ASCRR correction did not improve diagnostic performance significantly although the diagnostic specificity for RCA lesions improved on quantitative myocardial SPECT. The clinical application of the ASC-RR correction requires more discretion regarding cost and efficacy.
Min Jae Cha;William D Kim;Hoyoun Won;Jaeeun Joo;Hasung Kim;In-Cheol Kim;Jin Young Kim;Seonhwa Lee;Iksung Cho
Korean Circulation Journal
/
v.52
no.11
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pp.814-825
/
2022
Background and Objectives: Real-world trends in the utility and type of gatekeeping studies in invasive coronary angiography (ICA) requires further investigation. Methods: We identified outpatients who underwent noninvasive cardiac tests or directly ICA for suspected coronary artery disease (CAD) from the nationwide Korea Health Insurance Review and Assessment Service-National Patient Sample database between 2012 and 2018. Results: Among 71,401 patients, the percentage of patients who were evaluated for suspected CAD was 34.7% for treadmill test (TMT), 4.2% for single-photon emission computed tomography (SPECT), 24.2% for coronary computed tomography angiography (CCTA), 1.6% for multiple gatekeepers, and 32.3% for directly ICA without noninvasive studies. The proportion of CCTA as a gatekeeper showed linear increase, (18.6% in 2012 and 28.8% in 2018; p<0.001), while those of TMT, SPECT, and direct ICA have decreased (p<0.001, p=0.03, and p<0.001, respectively). The overall incidence of downstream ICA after gatekeeper was 13.8% (6,662/48,346), and SPECT showed higher ICA rate in pairwise comparison with TMT and CCTA (p<0.001). Patients who performed gatekeepers before ICA showed higher rate of subsequent PCI (34.7% vs. 32.3%; p<0.001) and CABG (3.5% vs. 1.0%; p<0.001), compared to those who directly underwent ICA, and CCTA was associated with higher revascularization rate after ICA in pairwise comparison with TMT and SPECT (p<0.001). Conclusions: Nationwide database demonstrated that CCTA is utilized increasingly as a gatekeeper for ICA and is associated with high revascularization rate after ICA in outpatients with suspected CAD.
Seo, Ji-Hyoung;Kang, Seong-Min;Bae, Jin-Ho;Jeong, Shin-Young;Lee, Sang-Woo;Yoo, Jeong-Soo;Ahn, Byeong-Cheol;Lee, Jae-Tae
Nuclear Medicine and Molecular Imaging
/
v.40
no.3
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pp.155-162
/
2006
Purpose: Diabetes mellitus (DM) is a critical disease with higher rates of cardiovascular morbidity and mortality due to myocardial ischemia and infarction. There is glowing interest in how to determine high-risk patients who are candidates for screening testing. This study was performed to evaluate the incidence of coronary artery disease (CAD) in diabetic patients detected by Tc-99m MIBI myocardial perfusion SPECT (MPS) and to assess risk factors of CAD and cardiac hard events. Subjects and Methods: 203 diabetic patients (64 male, mean age $64.1{\pm}9.0$ years) who underwent MPS were included between Jan 2000 and July 2004. Cardiac death and nonfatal myocardial infarction (MI) were considered as hard events, and coronary angioplasty and bypass surgery >60 days after testing were considered as soft events. The mean follow-up period was $36{\pm}18$ months. Patients underwent exercise (n=6) or adenosine stress (n=197) myocardial perfusion SPECT. Results: Perfusion defects on MPS were detected in 28.6% (58/203) of the patients. There was no cardiac death but 11 hard events were observed. The annual cardiac hard event rate was 1.1%. In univariate analysis of clinical factors, typical anginal pain, peripheral vascular disease, peripheral polyneuropathy, and resting ECG abnormality were significantly associated with the ocurrence of hard events. Anginal pain, peripheral vascular disease, and resting ECG abnormality remained independent predictors of nonfatal MIs with multivariate analysis. Abnormal SPECT results were significantly associated with high prevalence of hard events but not independent predictors on uni- and multivariate analyses. Conclusion: Patients who were male, had longer diabetes duration (especially over 20 years), peripheral vascular disease, peripheral polyneuropathy, or resting ECG abnormality had higher incidence of CAD. Among clinical factors in diabetic patients, typical angina, peripheral vascular disease, peripheral polyneuropathy, and resting ECG abnormality were strong predictors of hard events.
Coronary artery disease (CAD) and atrial fibrillation (AF) are known to share many risk factors. In particular, in the case of acute coronary syndrome, it may be difficult to clearly determine the diameter of the vessel due to complete occlusion of the vessel and thrombus. Thus, the relationship between the diameter of the coronary arteries was evaluated to be used as a reference data before the treatment of coronary arteries and drug selection in patients with AF. From January 2020 to August 2022, images of coronary angiography (CAG) with AF and normal sinus rhythm (NSR) on electrocardiography were target. In both subjects, images of normal coronary artery without lesions as a result of CAG were used. For all vessels, the diameters of the vessels were measured by dividing them into proximal, middle, and distal parts, and the measured diameters were divided by the average for evaluation. As a result of analyzing the left anterior descending artery diameter, the vessel diameter of the AF patient was 2.24±0.26 mm, which was smaller than that of the NSR patient, 2.86±0.38 mm, and was statistically significant. (p<0.001) As a result of analyzing the left circumflex artery diameter, the vessel diameter of the AF patient was 2.34±0.28 mm, which was smaller than the vessel diameter of the NSR patient, 2.87±0.29 mm, and was statistically significant. (p<0.001) As a result of analyzing the diameter of the right coronary artery, the vessel diameter of the AF patient was 2.68±0.5 mm, which was smaller than the vessel diameter of the NSR patient, 3.35±0.4 mm, and was statistically significant. (p<0.001) Considering that the coronary artery size of AF patients is significantly smaller than the coronary vessel size of NSR patients, it is considered as a useful study to be used as a reference for evaluating coronary artery diameter when the arrhythmia is AF. In particular, it is considered to be a study that can be helpful in diagnosing lesions, using drugs before and after surgery, and choosing to use auxiliary devices such as intravascular ultrasound.
Kim, Gwang-Weon;Choi, Chung-Il;Chung, Byung-Cheon;Lee, Jae-Tae;Lee, Kyu-Bo;Chae, Shung-Chull;Jun, Jae-Eun;Park, Wee-Hyun;Park, Hee-Myung
The Korean Journal of Nuclear Medicine
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v.25
no.1
/
pp.27-36
/
1991
Thirty-one patients with coronary artery disease and twenty-sir normal subjects underwent $^{99m}Tc-GBPS$ before and after coronary vasodilatation was induced by dipyridamle 0.54 mg/kg given IV over 4 min. LVEF, ${\Delta}EF$ and regional wall motion by phase analysis were measured during rest and dipyridamole infusion. The results were as follows: 1) Mean LVEF of normal subjects was significantly higher than that of MI group (p=0.001), but similar to that of angina group during rest. Among MI group, mean LVEF of anterior MI group was significantly lower than that of inferior MI group during rest (p=0.024). 2) The normal subjects had a significaat increase in mean LVEF during dipyridamole infusion $(+12{\pm}3.8)$, while the CAD group had no increase $(+2{\pm}5.0)$ (p<0.001). If an increase of LVEF during stress is less than 5%, it suggests an abnormality. The sensitivity and specificity of LVEF changes after dipyridamole infusion were 81%, 96%, respectively. 3) With phase analysis, LV mean phase angle of normal subjects and CAD patients was $143{\pm}20.5^{\circ},\;132{\pm}20.6^{\circ}$ respectively, durign rest (p=0.049). But an ncrease of LV mean phase angle during dipyridamole infusion in these two groups was not significantly different. Dipyridamole infusion did not affect standard deviation and FWHM of phase angle. 4) Regional wall motion was abnormal in 5 patients (16%) during dipyridamole infusion. 5) Side effects with dipyridamole infusion include; headache, angina pain, chest discomfirt, nausea, weakness sense. In conclusion, dipyridamole GBPS might be useful in detection and follow up of CAD.
Purpose: Aim of this study is to report real-life experience on the treatment of peripheral artery disease (PAD) with a specific drug-coated balloon (DCB), and to evaluate potential prognostic factors for outcomes. Materials and Methods: This is a retrospective study reporting outcomes in patients with PAD who were treated with the Lutonix DCB during a four-year period. Major outcomes included: all-cause mortality, amputation, clinical improvement, wound healing and target lesion revascularization (TLR). Mean follow-up was $24.2{\pm}2.3$ months. Results: Overall, 149 patients (mean age: $68.6{\pm}8.3$ years; 113 males) were treated, either for intermittent claudication (IC) (n=86) or critical limb ischemia (CLI) (n=63). More than half the target lesions (n=206 in total) were located in the superficial femoral artery and 18.0% were below-the-knee lesions. CLI patients presented more frequently with infrapopliteal (P=0.002) or multilevel disease (P=0.0004). Overall, all-cause mortality during follow-up was 10.7%, amputation-free survival was 81.2% and TLR-free survival was 96.6%. CLI patients showed higher all-cause mortality (P=0.007) and total amputation (P=0.0001) rates as well as lower clinical improvement (P=0.0002), compared to IC patients. Coronary artery disease (CAD), gangrene and infrapopliteal disease were found to be predictors for death whereas CLI and gangrene were found to be predictors for amputation, during follow-up. Conclusion: PAD treatment with Lutonix DCBs seems to be an efficient and safe endovascular strategy yielding promising results. However, CAD, gangrene, CLI and infrapopliteal lesions were found to be independent predictors for adverse outcomes. Larger series are needed to identify additional prognostic factors.
The genetic factors that contribute to the development of coronary artery disease (CAD) are poorly understood. It is likely that multiple genes that act independently or synergistically contribute to the development of CAD and the outcome. Recently, an insertion/deletion (I/D) polymorphism of the human angiotensin I-converting enzyme (ACE) gene, a major component of the renin-angiotensin system (RAS), was identified. The association of the ACE gene D allele with essential hypertension and CAD has been reported in the African-American, Chinese, and Japanese populations. However, other studies have failed to detect such an association. It has been suggested that these inconsistencies may be due to the difference in backgrounds of the population characteristics. In the present study, we investigated the I/D polymorphism of the ACE gene in 103 subjects of both sexes, consisting of 59 normal controls and 44 patients with hypertension. The allele and genotype frequency were significantly different between the hypertensive and control groups (p < 0.01). Among the three ACE I/D variants, the DD genotype was associated with the highest value of the mean systolic blood pressure [SBP] and mean diastolic blood pressure [DBP] (p = < 0.05) in men, but not in women. In the overall population, the mean SBP and DBP was highest in DD subjects, intermediate in I/D subjects, and the least in II subjects.
Chae, Cheol Byoung;Ha, Ju Hee;Kim, Jun Ho;Lee, Jae Joon;Choi, Han Il;Park, Ki Beom;Kim, Jin Hee;Choi, Jung Hyun
Kosin Medical Journal
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v.33
no.3
/
pp.328-336
/
2018
Objectives: Electrocardiograhy (ECG) is the first step in hypertrophic cardiomyopathy (HCMP) diagnosis. For various reasons, the T wave inversion (TWI) and ECG change with time and HCMP is not easy to diagnosis. The aim of this retrospective study was to investigate the association between TWI on ECG and apical HCMP. Methods: A total of 4,730 ECGs presenting TWI from January 2011 to March 2013 in Pusan National University Hospital were enrolled. 133 patients who were examined by both echocardiography and coronary angiogram were analyzed. Patients were divided into two groups: Group A (TWI ${\geq}$ 10 mm) and Group B (5 mm ${\leq}$ TWI < 10 mm). HCMP is defined by a wall thickness ${\geq}15mm$ in one or more LV myocardial segments. Apical HCMP is defined to be hypertrophy that is confined to LV apex. The patients who had ECGs with at least one month interval were divided 3 groups: Normal T wave, Abnormal T wave, and Persistent TWI. The prevalence of Apical HCMP and coronary artery disease (CAD) was reviewed among the three groups. Results: In this study there were a total 133 patients, with patients divided into Group A which had 15 patients and Group B which had 118 patients. Among the 23 patients with apical HCMP, three patients were Group A and twenty patients were Group B (P = 0.769). Regarding constancy of TWI, persistent TWI group was higher in apical HCMP than in other groups (P = 0.038). CAD had no difference between groups (P = 0.889). Conclusions: T wave negativity was not associated with incidence of apical HCMP. However, apical HCMP was diagnosed more frequently in patients with persistent TWI. Further follow up echocardiographic study is needed to evaluate the progression of apical HCMP in patients with TWI.
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