• Korean Journal of Radiology
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• v.24 no.5
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• pp.395-405
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• 2023

Objective: This study aimed to develop and validate models using radiomics features on a native T1 map from cardiac magnetic resonance (CMR) to predict left ventricular reverse remodeling (LVRR) in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods: Data from 274 patients with NIDCM who underwent CMR imaging with T1 mapping at Severance Hospital between April 2012 and December 2018 were retrospectively reviewed. Radiomic features were extracted from the native T1 maps. LVRR was determined using echocardiography performed ≥ 180 days after the CMR. The radiomics score was generated using the least absolute shrinkage and selection operator logistic regression models. Clinical, clinical + late gadolinium enhancement (LGE), clinical + radiomics, and clinical + LGE + radiomics models were built using a logistic regression method to predict LVRR. For internal validation of the result, bootstrap validation with 1000 resampling iterations was performed, and the optimism-corrected area under the receiver operating characteristic curve (AUC) with 95% confidence interval (CI) was computed. Model performance was compared using AUC with the DeLong test and bootstrap. Results: Among 274 patients, 123 (44.9%) were classified as LVRR-positive and 151 (55.1%) as LVRR-negative. The optimism-corrected AUC of the radiomics model in internal validation with bootstrapping was 0.753 (95% CI, 0.698-0.813). The clinical + radiomics model revealed a higher optimism-corrected AUC than that of the clinical + LGE model (0.794 vs. 0.716; difference, 0.078 [99% CI, 0.003-0.151]). The clinical + LGE + radiomics model significantly improved the prediction of LVRR compared with the clinical + LGE model (optimism-corrected AUC of 0.811 vs. 0.716; difference, 0.095 [99% CI, 0.022-0.139]). Conclusion: The radiomic characteristics extracted from a non-enhanced T1 map may improve the prediction of LVRR and offer added value over traditional LGE in patients with NIDCM. Additional external validation research is required.

• Endocrinology and Metabolism
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• v.33 no.4
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• pp.485-492
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• 2018

Background: Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA. Methods: Forty-two patients (mean age $48.8{\pm}10.9$ years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins. Results: The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was $8.9{\pm}0.3mg/dL$ (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ${\rho}=-0.424$, P=0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (${\beta}=-0.366$, P=0.068 and ${\beta}=-0.252$, P=0.070, respectively). Conclusion: Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.

• Journal of Veterinary Clinics
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• v.27 no.6
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• pp.735-739
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• 2010

An 8 month old female Maltese (body weight 3.6 kg) was referred with primary complaints of dyspnea and exercise intolerance. Diagnostic imaging studies revealed marked cardiomegaly and prominent main pulmonary trunk dilation on thoracic radiography, abnormally arisen aortic roots (toward right ventricle) with left-to right shunted perimembraneous ventricular septal defect located underneath of aortic root, aortic root was located to predominantly to the right ventricle and pulmonary regurgitation (peak velocity 4.7 m/s, pressure gradient ~88 mmHg) from pulmonary over-circulation and hypertension on echocardiography, indicating double outlet right ventricle (DORV). The dog was treated with furosemide (1 mg/kg, BID) for reducing volume overload at right ventricle, spironolatcone (1 mg/kg) and enalapril (0.5 mg/kg) for minimizing deleterious cardiac remodeling, and sildenafil (1 mg/kg) for lessening pulmonary over-circulation and hypertension. The clinical condition of this dog was improved after 1 week of medical treatment. The dog is currently survived and regularly monitored.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.482-489
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• 2020

G protein-coupled receptor kinase 5 (GRK5) has been considered as a potential target for the treatment of heart failure as it has been reported to be an important regulator of pathological cardiac hypertrophy. To discover novel scaffolds that selectively inhibit GRK5, we have identified a novel small molecule inhibitor of GRK5, KR-39038 [7-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-2-(2-chlorophenyl)-6-fluoroquinazolin-4(3H)-one]. KR-39038 exhibited potent inhibitory activity (IC₅₀ value=0.02 µM) against GRK5 and significantly inhibited angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes. In the pressure overload-induced cardiac hypertrophy mouse model, the daily oral administration of KR-39038 (30 mg/kg) for 14 days showed a 43% reduction in the left ventricular weight. Besides, KR-39038 treatment (10 and 30 mg/kg/day, p.o.) showed significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure following coronary artery ligation. These results suggest that potent GRK5 inhibitor could effectively attenuate both cardiac hypertrophy and dysfunction in experimental heart failure, and KR-39038 may be useful as an effective GRK5 inhibitor for pharmaceutical applications.

• Herbal Formula Science
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• v.30 no.3
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• pp.123-135
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• 2022

Oryeongsan (ORS), a formula composed of five herbal medicines, has long been used to treat impairments of the regulation of body fluid homeostasis. The purpose of this study was to determine the antihypertensive and renal protective effects of ORS in rats with hypertension. Spontaneously hypertensive rats (SHR) were divided into two groups with similar mean baseline systolic blood pressure (SBP). Then, 1 mL/kg of vehicle (distilled water) or 1.5, 3 g/kg of ORS extract were administered orally once a day for 4 weeks. SBP and diastolic blood pressure (DBP) were measured at weeks 1, 2, 3 and 4. At the end of the experiment, blood was collected, and heart were removed for histology. By the 2 weeks after initiation of treatment, the ORS treated group had significantly lower SBP than SHR rats. The ORS treatment significantly improved blood pressure and echocardiogram parameters compared to hypertensive rats. Additionally, the left ventricular (LV) remodeling and LV dysfunction were significantly improved in ORS treated group hypertensive rats. Furthermore, an increase in fibrotic area has been observed in SHR rats compared with Wistar-Kyoto rats (WKY). Furthermore, administration of ORS significantly attenuated cardiac fibrosis in hypertensive rats. Therefore, these findings suggest that ORS has a protective effect on heart failure by alleviating hypertensive heart disease and cardiovascular dysfunction in SHR.

• Clinical and Experimental Pediatrics
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• v.53 no.1
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• pp.41-47
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• 2010

Purpose : Adiponectin is an endogenous modulator of vascular remodeling that suppresses vascular inflammation. However, the role of adiponectin in Kawasaki disease (KD) has not been elucidated. The purpose of this study is to investigate the correlation between serum adiponectin level and several parameters, such as interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, lipid profile, and C reactive protein (CRP), and to clarify the association between adiponectin and cardiac function. Methods : Twenty-two KD patients (22 patients in acute phase and 20 patients in subacute phase) were enrolled in the study group. The control group consisted of 31 subjects (13 febrile patients and 18 healthy children). Both groups underwent blood sampling and tissue Doppler imaging (TDI). Results : CRP was significantly increased in the KD group compared with the control group. There were no significant differences in serum $TNF-{\alpha}$, IL-6, and adiponectin levels between groups. However, a negative correlation was found between adiponectin level and CRP level or platelet count. Systolic myocardial velocity and A myocardial velocity measured by TDI were decreased significantly in the acute KD group compared with the subacute KD group and control group. Positive correlations were found between adiponectin level and systolic myocardial velocity or A myocardial velocity. Conclusion : In acute KD patients, low adiponectin level was related to severe inflammatory reactions and decreased left ventricular functions.

• Journal of Chest Surgery
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• v.39 no.3 s.260
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• pp.226-229
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• 2006

Recently, heart transplantation has been accepted as a standard treatment for infant and children with end-stage cardiomyopathy or complex congenital heart disease. Due to the shortage of donors, size-mismatched cardiac transplantation is common. After size-mismatched transplantation, there could be side-effects such as hypertension and hypertensive encephalopathy because of the big-heart. Donor heart is also known to do remodel as time goes by. This is a case report of a size-mismatched heart transplantation between 9-year-old boy and a 39-year-old female whose body weight is almost twice of him. In this case, classical postoperative hypertension and hypertensive encephalopathy developed but was successfully managed. The donor heart has remodeled to normal dimension during 3 years follow-up period.

• Journal of Chest Surgery
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• v.38 no.5 s.250
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• pp.323-334
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• 2005

Background: Gene therapy is a new and promising option for the treatment of severe myocardial ischemia by therapeutic angiogenesis. The goal of this study was to elucidate the efficacy of therapeutic angiogenesis by using VEGF165 in large animals. Material and Method: Twenty-one pigs that underwent ligation of the distal left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF (VEGF) or intramyocardial injection of pCK-Null (Control). Injections were administered 30 days after ligation. Seven pigs died during the trial, but eight pigs from VEGF and six from Control survived. Echo-cardiography was performed on day 0 (preoperative) and on days 30 and 60 following coronary ligation. Gated myocardial single photon emission computed tomography imaging (SPECT) with $^{99m}Tc-labeled$ sestamibi was performed on days 30 and 60. Myocardial perfusion was assessed from the uptake of $^{99m}Tc-labeled$ sestamibi at rest. Global and regional myocardial function as well as post-infarction left ventricular remodeling were assessed from segmental wall thickening; left ventricular ejection fraction (EF); end systolic volume (ESV); and end diastolic volume (EDV) using gated SPECT and echocardiography. Myocardium of the ischemic border zone into which pCK plasmid vector had been injected was also sampled to assess micro-capillary density. Result: Micro-capillary density was significantly higher in the VEGF than in Control ($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2};\;p<0.001$). Segmental perfusion increased significantly from day 30 to day 60 after intramyocardial injection of plasmid vector in VEGF ($48.4\pm15.2\%\;vs.\;53.8\pm19.6\%;\;p<0.001$), while no significant change was observed in the Control ($45.1\pm17.0\%\;vs.\;43.4\pm17.7\%;\;p=0.186$). This resulted in a significant difference in the percentage changes between the two groups ($11.4\pm27.0\%\;increase\;vs.\;2.7\pm19.0\%\;decrease;\;p=0.003$). Segmental wall thickening increased significantly from day 30 to day 60 in both groups; the increments did not differ between groups. ESV measured using echocardiography increased significantly from day 0 to day 30 in VEGF ($22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL;\; p=0.006$) and in Control ($26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL;\;p=0.046$). EF decreased significantly in VEGF ($52.0\pm7.7\%\;vs.\;46.5\pm7.4\%;\;p=0.004$) and in Control ($48.2\pm9.2\%\;vs.\;41.6\pm10.0\%;\;p=0.028$). There was no significant change in EDV. The interval changes (days $30\~60$) of EF, ESV, and EDV did not differ significantly between groups both by gated SPECT and by echocardiography. Conclusion: Intramyocardial injection of pCK-VEGF165 induced therapeutic angiogenesis and improved myocardial perfusion. However, post-infarction remodeling and global myocardial function were not improved.

• Journal of Chest Surgery
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• v.42 no.1
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• pp.28-33
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• 2009

Background: Functional tricuspid regurgitation (TR) greater than or equal to a mild grade requires tricuspid valvuloplasty, and tricuspid valvuloplasty with ring annuloplasty has shown good outcomes. We report here on our early experience with the Edwards $MC^3$ annuloplasty system (Edwards LifeSciences, Irvine, CA). Material and Method: From November 2004 to July 2006, 72 patients with tricuspid annular dilatation and TR underwent tricuspid valvuloplasty with using the Edwards $MC^3$ annuloplasty ring. Sixty-eight patients were operated on via median sternotomy and four patients were operated on using robotic assisted minimal invasive thoracotomy. The patient population included 21 males and 51 females and their mean age was $53.9{\pm}12.3$. The mean grade of TR, as assessed by the preoperative echocardiography, was $2.2{\pm}1.0$. The mean NYHA functional class was $3.1{\pm}0.8$. The mean left ventricular ejection fraction was $57.0{\pm}9.9$%. Result: The TR and NYHA functional class, as assessed by postoperative echocardiography, was significantly reduced (mean=$0.4{\pm}0.6$ and $2.0{\pm}0.7$, respectively p<0.001). There was one case of hospital mortality. One patient required permanent pacemaker insertion for third degree atrioventricular block. Conclusion: Our study shows that the Edwards $MC^3$ remodeling ring is easy to implant and it effectively corrects functional TR with excellent clinical and echocardiographic outcomes. Further follow-up and a larger clinical series are required to establish the long-term stability of this repair technique.