• Journal of Chest Surgery
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• v.50 no.3
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• pp.144-152
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• 2017

Background: The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of $NF-{\kappa}B$ and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model. Methods: We constructed a transverse aortic constriction (TAC)-induced LVH rat model with 3 groups: sham (TAC-sham, n=10), control (TAC-cont, n=10), and MG132 administration (TAC-MG132, n=10). MG-132 (0.1 mg/kg) was injected for 4 weeks in the TAC-MG132 group. Pathophysiologic evaluations were performed and the expression of AR and $NF-{\kappa}B$ was measured in the left ventricle. Results: Fibrosis was prevalent in the pathologic examination of the TAC-cont model, and it was reduced in the TAC-MG132 group, although not significantly. Less expression of AR, but not $NF-{\kappa}B$, was found in the TAC-MG132 group than in the TAC-cont group (p<0.05). Conclusion: MG-132 was found to suppress AR in the TAC-CMP model by blocking the UPS, which reduced fibrosis. However, $NF-{\kappa}B$ expression levels were not related to UPS function.

• Korean Circulation Journal
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• v.54 no.8
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• pp.468-481
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• 2024

Background and Objectives: Although the clinical consequences of advanced heart failure (HF) may be similar across different etiologies of cardiomyopathies, their proteomic expression may show substantial differences in relation to underlying pathophysiology. We aimed to identify myocardial tissue-based proteomic characteristics and the underlying molecular pathophysiology in non-ischemic cardiomyopathy with different etiologies. Methods: Comparative extensive proteomic analysis of the myocardium was performed in nine patients with biopsy-proven non-ischemic cardiomyopathies (3 dilated cardiomyopathy [DCM], 2 hypertrophic cardiomyopathy [HCM], and 4 myocarditis) as well as five controls using tandem mass tags combined with liquid chromatography-mass spectrometry. Differential protein expression analysis, Gene Ontology (GO) analysis, and Ingenuity Pathway Analysis (IPA) were performed to identify proteomic differences and molecular mechanisms in each cardiomyopathy type compared to the control. Proteomic characteristics were further evaluated in accordance with clinical and pathological findings. Results: The principal component analysis score plot showed that the controls, DCM, and HCM clustered well. However, myocarditis samples exhibited scattered distribution. IPA revealed the downregulation of oxidative phosphorylation and upregulation of the sirtuin signaling pathway in both DCM and HCM. Various inflammatory pathways were upregulated in myocarditis with the downregulation of Rho GDP dissociation inhibitors. The molecular pathophysiology identified by extensive proteomic analysis represented the clinical and pathological properties of each cardiomyopathy with abundant proteomes. Conclusions: Different etiologies of non-ischemic cardiomyopathies in advanced HF exhibit distinct proteomic expression despite shared pathologic findings. The benefit of tailored management strategies considering the different proteomic expressions in non-ischemic advanced HF requires further investigation.

• Kosin Medical Journal
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• v.33 no.3
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• pp.328-336
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• 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.

• Korean Journal of Radiology
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• v.22 no.7
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• pp.1044-1053
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• 2021

Objective: Motion-corrected averaging with a single-shot technique was introduced for faster acquisition of late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging while free-breathing. We aimed to evaluate the image quality (IQ) of free-breathing motion-corrected single-shot LGE (moco-ss-LGE) in patients with hypertrophic cardiomyopathy (HCM). Materials and Methods: Between April and December 2019, 30 patients (23 men; median age, 48.5; interquartile range [IQR], 36.5-61.3) with HCM were prospectively enrolled. Breath-held single-shot LGE (bh-ss-LGE) and free-breathing moco-ss-LGE images were acquired in random order on a 3T MR system. Semi-quantitative IQ scores, contrast-to-noise ratios (CNRs), and quantitative size of myocardial scar were assessed on pairs of bh-ss-LGE and moco-ss-LGE. The mean ± standard deviation of the parameters was obtained. The results were compared using the Wilcoxon signed-rank test. Results: The moco-ss-LGE images had better IQ scores than the bh-ss-LGE images (4.55 ± 0.55 vs. 3.68 ± 0.45, p < 0.001). The CNR of the scar to the remote myocardium (34.46 ± 11.85 vs. 26.13 ± 10.04, p < 0.001), scar to left ventricle (LV) cavity (13.09 ± 7.95 vs. 9.84 ± 6.65, p = 0.030), and LV cavity to remote myocardium (33.12 ± 15.53 vs. 22.69 ± 11.27, p < 0.001) were consistently greater for moco-ss-LGE images than for bh-ss-LGE images. Measurements of scar size did not differ significantly between LGE pairs using the following three different quantification methods: 1) full width at half-maximum method; 23.84 ± 12.88% vs. 24.05 ± 12.81% (p = 0.820), 2) 6-standard deviation method, 15.14 ± 10.78% vs. 15.99 ± 10.99% (p = 0.186), and 3) 3-standard deviation method; 36.51 ± 17.60% vs. 37.50 ± 17.90% (p = 0.785). Conclusion: Motion-corrected averaging may allow for superior IQ and CNRs with free-breathing in single-shot LGE imaging, with a herald of free-breathing moco-ss-LGE as the scar imaging technique of choice for clinical practice.

• Korean Journal of Radiology
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• v.22 no.7
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• pp.1054-1065
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• 2021

Objective: We implemented a novel resectable myocardial model for mock myectomy using a hybrid method of three-dimensional (3D) printing and silicone molding for patients with apical hypertrophic cardiomyopathy (ApHCM). Materials and Methods: From January 2019 through May 2020, 3D models from three patients with ApHCM were generated using the end-diastolic cardiac CT phase image. After computer-aided designing of measures to prevent structural deformation during silicone injection into molding, 3D printing was performed to reproduce anatomic details and molds for the left ventricular (LV) myocardial mass. We compared the myocardial thickness of each cardiac segment and the LV myocardial mass and cavity volumes between the myocardial model images and cardiac CT images. The surgeon performed mock surgery, and we compared the volume and weight of the resected silicone and myocardium. Results: During the mock surgery, the surgeon could determine an ideal site for the incision and the optimal extent of myocardial resection. The mean differences in the measured myocardial thickness of the model (0.3, 1.0, 6.9, and 7.3 mm in the basal, midventricular, apical segments, and apex, respectively) and volume of the LV myocardial mass and chamber (36.9 mL and 14.8 mL, 2.9 mL and -9.4 mL, and 6.0 mL and -3.0 mL in basal, mid-ventricular and apical segments, respectively) were consistent with cardiac CT. The volume and weight of the resected silicone were similar to those of the resected myocardium (6 mL [6.2 g] of silicone and 5 mL [5.3 g] of the myocardium in patient 2; 12 mL [12.5 g] of silicone and 11.2 mL [11.8 g] of the myocardium in patient 3). Conclusion: Our 3D model created using hybrid 3D printing and silicone molding may be useful for determining the extent of surgery and planning surgery guided by a rehearsal platform for ApHCM.

• Journal of Cardiovascular Imaging
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• v.31 no.2
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• pp.85-95
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• 2023

BACKGROUND: The prognostic utility of follow-up transthoracic echocardiography (FU-TTE) in patients with hypertrophic cardiomyopathy (HCM) is unclear, specifically in terms of whether changes in echocardiographic parameters in routine FU-TTE parameters are associated with cardiovascular outcomes. METHODS: From 2010 to 2017, 162 patients with HCM were retrospectively enrolled in this study. Using echocardiography, HCM was diagnosed based on morphological criteria. Patients with other diseases that cause cardiac hypertrophy were excluded. TTE parameters at baseline and FU were analyzed. FU-TTE was designated as the last recorded value in patients who did not develop any cardiovascular event or the latest exam before event development. Clinical outcomes were acute heart failure, cardiac death, arrhythmia, ischemic stroke, and cardiogenic syncope. RESULTS: Median interval between the baseline TTE and FU-TTE was 3.3 years. Median clinical FU duration was 4.7 years. Septal trans-mitral velocity/mitral annular tissue Doppler velocity (E/e'), tricuspid regurgitation velocity, left ventricular ejection fraction (LVEF), and left atrial volume index (LAVI) at baseline were recorded. LVEF, LAVI, and E/e' values were associated with poor outcomes. However, no delta values predicted HCM-related cardiovascular outcomes. Logistic regression models incorporating changes in TTE parameters had no significant findings. Baseline LAVI was the best predictor of a poor prognosis. In survival analysis, an already enlarged or increased size LAVI was associated with poorer clinical outcomes. CONCLUSIONS: Changes in echocardiographic parameters extracted from TTE did not assist in predicting clinical outcomes. Cross-sectionally evaluated TTE parameters were superior to changes in TTE parameters between baseline and FU at predicting cardiovascular events.

• Journal of Chest Surgery
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• v.27 no.4
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• pp.313-317
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• 1994

Surgical treatment is possible for the obstructive form of hypertrophic cardiomyopathy and transaortic left ventricular septal myectomy and myotomy has been the procedure of choice. If coexisting intrinsic mitral valve disease exists, mitral valve replacement has been performed. But abnormal systolic anterior motion of anterior mitral leaflet[SAM] with intrinsic normal mitral valve disease is the typical feature of IHSS and we prefer not to replace mitral valve. 3 patients underwent transaortic myotomy and myectomy for IHSS with mitral regurgitation. 2 patients of them have coexisting intrinsic mitral valve diseases such as mitral valve vegetation and chorda rupture. Concomittent mitral valve replacement were performed. 1 patient shows SAM of mitral anterior leaflet but has intrinsic normal mitral valve morphologically and transepicardial echocardiogram and direct monitoring of pressure gradient during the operative procedure gives better information for subsided mitral regurgitation. Post operative course during the 12 months follow-up was uneventful.

• Journal of Chest Surgery
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• v.43 no.5
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• pp.522-524
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• 2010

Cardiac transplantation in a patient with persistent left superior vena cava (SVC) necessitates unifocalization of the caval veins. Here we report a successful case of orthotopic heart transplantation in a patient with hypertrophic cardiomyopathy and persistent left SVC. Cardiac transplantation was done after the left SVC was anastomosed to the right SVC in an end to side fashion. The postoperative course was uneventful, and the patient is currently in an excellent clinical condition.

• Clinical and Experimental Pediatrics
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• v.50 no.10
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• pp.1024-1029
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• 2007

Costello syndrome (CS) is a rare multiple congenital abnormality syndrome characterized by a typical coarse face, developmental delay, psychomotor and growth retardation, neurologic abnormalities, cardiac and cutaneous anomalies, severe feeding difficulties with postnatal growth failure, and increased risk of tumors. Since Costello first described it in 1971 and again in 1977, over 100 cases have been reported worldwide. It was recently shown that CS is a congenital condition caused by heterozygous de novo missense mutations affecting the codon for glycine 12 or 13 of the HRAS gene. We experienced three unrelated cases with coarse faces, developmental delays, short statures, macrocephaly, and redundant skin with deep palmar and plantar creases, hypertrophic cardiomyopathy and atrial tachycardia, which are characteristic of CS.

• Journal of Genetic Medicine
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• v.13 no.2
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• pp.99-104
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• 2016

$Cant{\acute{u}}$ syndrome (CS, OMIM 239850) is a very rare autosomal dominantly inherited genetic disease characterized by congenital hypertrichosis, neonatal macrosomia, a distinct facial features such as macrocephaly, and cardiac defects. Since the first description by $Cant{\acute{u}}$ et al. in 1982, about 50 cases have been reported to date. Recently, two causative genes for CS has been found by using exome sequencing analyses: ABCC9 and KCNJ8. Most cases of clinically diagnosed CS have resulted from de novo mutations in ABCC9. In this study, we report three independent Korean children with CS resulting from de novo ABCC9 mutations. Our patients had common clinical findings such as congenital hypertrichosis, distinctive facial features. One of them showed severe pulmonary hypertension and hypertrophic cardiomyopathy, which require medical treatment. And, two patients had a history of patent ductus arteriosus. Although two of our patients had shown early motor developmental delay, it was gradually improved during follow-up periods. Although CS is quite rare, there are the concerns about development of various cardiac problems in the lifetime. Therefore, an accurate diagnosis followed by appropriate management and genetic counseling should be provided to CS patients.