Genetic Variations Leading to Familial Dilated Cardiomyopathy

Cho, Kae Won,Lee, Jongsung,Kim, Youngjo Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.10

Cardiomyopathy is a major cause of death worldwide. Based on pathohistological abnormalities and clinical manifestation, cardiomyopathies are categorized into several groups: hypertrophic, dilated, restricted, arrhythmogenic right ventricular, and unclassified. Dilated cardiomyopathy, which is characterized by dilation of the left ventricle and systolic dysfunction, is the most severe and prevalent form of cardiomyopathy and usually requires heart transplantation. Its etiology remains unclear. Recent genetic studies of single gene mutations have provided significant insights into the complex processes of cardiac dysfunction. To date, over 40 genes have been demonstrated to contribute to dilated cardiomyopathy. With advances in genetic screening techniques, novel genes associated with this disease are continuously being identified. The respective gene products can be classified into several functional groups such as sarcomere proteins, structural proteins, ion channels, and nuclear envelope proteins. Nuclear envelope proteins are emerging as potential molecular targets in dilated cardiomyopathy. Because they are not directly associated with contractile force generation and transmission, the molecular pathways through which these proteins cause cardiac muscle disorder remain unclear. However, nuclear envelope proteins are involved in many essential cellular processes. Therefore, integrating apparently distinct cellular processes is of great interest in elucidating the etiology of dilated cardiomyopathy. In this mini review, we summarize the genetic factors associated with dilated cardiomyopathy and discuss their cellular functions.

Genetic Variations Leading to Familial Dilated Cardiomyopathy

김영조,Kae Won Cho,Jongsung Lee 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.10

Cardiomyopathy is a major cause of death worldwide. Based on pathohistological abnormalities and clinical manifestation, cardiomyopathies are categorized into several groups: hypertrophic, dilated, restricted, arrhythmogenic right ventricular, and unclassified. Dilated cardiomyopathy, which is characterized by dilation of the left ventricle and systolic dysfunction, is the most severe and prevalent form of cardiomyopathy and usually requires heart transplantation. Its etiology remains unclear. Recent genetic studies of single gene mutations have provided significant insights into the complex processes of cardiac dysfunction. To date, over 40 genes have been demonstrated to contribute to dilated cardiomyopathy. With advances in genetic screening techniques, novel genes associated with this disease are continuously being identified. The respective gene products can be classified into several functional groups such as sarcomere proteins, structural proteins, ion channels, and nuclear envelope proteins. Nuclear envelope proteins are emerging as potential molecular targets in dilated cardiomyopathy. Because they are not directly associated with contractile force generation and transmission, the molecular pathways through which these proteins cause cardiac muscle disorder remain unclear. However, nuclear envelope proteins are involved in many essential cellular processes. Therefore, integrating apparently distinct cellular processes is of great interest in elucidating the etiology of dilated cardiomyopathy. In this mini review, we summarize the genetic factors associated with dilated cardiomyopathy and discuss their cellular functions.

Clomipramine에 의해 유발된 만성 확장성 심근증 1예

김응주,박창규,신성희,김진원,손장욱,강창돈,최창원,김병회,김현철,이승진,이은미,안정천,서홍석,오동주,노영무 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.8

확장성심근중 환자에서 Enalapril 치료가 좌심실내경의 순간변화율에 미치는 영향

김철우(Cheol Woo Kim),정유석(Yoo Suk Jung),이광제(Kwang Je Lee),곽미향(Mi Hyang Kwak),김경만(Kyung Man Kim),김태호(Tae Ho Kim),김치정(Chee Jeong Kim),류왕성(Wang Seong Ryu),유언호(Un Ho Ryoo) 대한내과학회 1997 대한내과학회지 Vol.52 No.5

N/A Objective: Angiotensin-converting enzyme inhibitors have been shown to improve survival in patients with congestive heart failure. To evaluate the efficacy of enalapril in patients with dilated cardiomyopathy during concurrent treatment with digoxin and diuretics, the peak rates of left ventricular movement were assessed after 6 months of follow-up by digitized echocardiography. Methods: Using a high quality digitizer, continuous measurement of left ventricular dimension and its rate of change (dD/dt) were obtained throughout the cardiac cycle. Normalized rates of wall movement (dD/dt/D) were used for comparison. Results: 1) Compared with control subjects, patients with dilated cardiomyopathy showed much lower Peak(-) dD/dt and Peak(-) dD/dt/D. 2) Peak(+) dD/dt and Peak(+) dD/dt/D were also depressed in patients. 3) Peak dD/dt improved significantly (p<0.05) in the enalapril group (n=16), but did not change in the conventional treatment group (n=20) after 6 months. Peak dD/dt/D improved approximately (p<0.005) in the enalapril group. 5) There were no deaths in 2 treatment groups during initial 6 months, but 3 patients in the conventional treatment group died suddenly during 1 year of follow-up. Conclusion: The present study has shown that left ventrieular Peak dD/dt and Peak dD/dt/D are significantly depressed in patients with dilated cardiomyopathy. Enalapril appears to provide well-tolerated and effective long-term therapy by improving peak rates of left ventricular movement in patients with dilated cardiomyopathy.

Cardiac Rehabilitation of a Patient With an Advanced Dilated Cardiomyopathy: A Case Report

Chul Kim,Hee Eun Choi,이병주 대한재활의학회 2014 Annals of Rehabilitation Medicine Vol.38 No.4

The dilated cardiomyopathy is the common type of cardiomyopathy, and its distinctive characteristic is the systolic dysfunction. Not many reports were issued about the efficacy of cardiac rehabilitation in patients with an advanced dilated cardiomyopathy until yet. A 50-year-old man who was diagnosed with dilated cardiomyopathy with congestive heart failure was admitted to the emergency room after a sudden collapse and a ventricular fibrillation was presented in the actual electrocardiogram. After three months, the patient participated in an 8-week cardiac rehabilitation program with electrocardiogram monitoring for 50 minutes per session at five times per week. The maximal oxygen consumption improved from 13.5 to 19.4 mL/kg/min during this time. At 3.9 metabolic equivalents, the myocardial oxygen demand decreased from 21,710 to 12,669 mmHg.bpm and the Borg’s scale of perceived exertion decreased from 15 to 9. The left ventricular ejection fraction improved from 14% to 19%. So in this case report will be presented a patient after a successful cardiac rehabilitation program. Before this the patient suffered from a much more advanced dilated cardiomyopathy and was resuscitated from cardiac arrest.

확장성 심근증이 병발한 전신성 홍반성 루푸스

정명선 ( Myung Sun Chung ),오은숙 ( Eun Suk Oh ),조은주 ( Eun Ju Cho ),민준기 ( Jun Ki Min ),홍연식 ( Yeon Sik Hong ),이상헌 ( Sang Heon Lee ),박성환 ( Sung Hwan Park ),조철수 ( Chul Soo Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 1997 대한류마티스학회지 Vol.4 No.1

SLE is an acute and/or chronic disease of a complex autoimmune nature affecting the skin, joints, serous membranes, kidney, central nervous system, cardiovascular system, and other organs of the body. Cardiac abnormalities are one of the most important clinical manifestations of SLE, contributing significantly to the morbidity and morality of the disease. We report a woman, a 30-year-old with SLE, who developed symptoms and echocardiographic signs of dilated cardiomyopathy. She had a history of acute myocardial infartion 7 months ago and has taken cyclophosphamide pulse therapy owing to lupus nephritis. The diagnosis of the condition was based only on clinical and echocardiographic grounds without coronary angiography or endomyocardial biopsy. She received high dose steroid (methylprednisolone pulse therapy: Img/kg for 3 days) and conservative therapy for heart failure. The association of SLE with dilated cardiomyopathy has not been described with review of previous literatures. For the probable causes of her dilated cardiomyopathy, we suggest that they are due to coronary arteritis or cyclophosphamide-induced myocarditis with regard to her past history of myocardial infartion and cyclophosphamide therapy for lupus nephritis. The incidence of dilated cardiomyopathy, complicated with SLE is rare, but it has an increased risk for untavorable outcome. It reserves to pioneer the method of early diagnosis and management which will improved the morbidity and mortality of the disease.

Prevalence, Characteristics, and Clinical Significance of Concomitant Cardiomyopathies in Subjects with Bicuspid Aortic Valves

정현주,심지영,김다래,최재연,최강운,이수연,홍그루,하종원 연세대학교의과대학 2019 Yonsei medical journal Vol.60 No.9

Purpose: The present study aimed to investigate the prevalence, characteristics, and clinical significance of concomitant specificcardiomyopathies in subjects with bicuspid aortic valves (BAVs). Materials and Methods: A total of 1186 adults with BAV (850 males, mean age 56±14 years) at a single tertiary center were comprehensivelyreviewed. Left ventricular non-compaction, hypertrophic cardiomyopathy, and idiopathic dilated cardiomyopathywere confirmed when patients fulfilled current clinical and echocardiographic criteria. Clinical and echocardiographic characteristics,including comorbidities, heart failure presentation, BAV morphology, function, and aorta phenotypes, in BAV subjectswith or without specific cardiomyopathies were compared. Results: Overall, 67 subjects (5.6%) had concomitant cardiomyopathies: 40 (3.4%) patients with left ventricular non-compaction,17 (1.4%) with hypertrophic cardiomyopathy, and 10 (0.8%) with dilated cardiomyopathy. BAV subjects with hypertrophic cardiomyopathyhad higher prevalences of diabetes mellitus and heart failure with preserved ejection fraction, and tended to havetype 0 phenotype, while BAV subjects with dilated cardiomyopathy showed higher prevalences of chronic kidney disease andheart failure with reduced ejection fraction. BAV subjects with left ventricular non-compaction were significantly younger andpredominantly male, and had greater BAV dysfunction and a higher prevalence of normal aorta shape. In multiple regressionanalysis, cardiomyopathy was independently associated with heart failure (odds ratio 2.795, 95% confidential interval 1.603–4.873, p<0.001) after controlling for confounding factors. Conclusion: Concomitant cardiomyopathies were observed in 5.6% of subjects with BAV. A few different clinical and echocardiographiccharacteristics were found. The presence of cardiomyopathy was independently associated with heart failure.

Genetics of Cardiomyopathy: Clinical and Mechanistic Implications for Heart Failure

Kyung-Hee Kim,Naveen L. Pereira 대한심장학회 2021 Korean Circulation Journal Vol.51 No.10

Genetics has played an important role in the understanding of different cardiomyopathies, and the field of heart failure (HF) genetics is progressing rapidly. Much research has also focused on distinguishing markers of risk in patients with cardiomyopathy using genetic testing. While these efforts currently remain incomplete, new genomic technologies and analytical strategies provide promising opportunities to further explore the genetic architecture of cardiomyopathies, afford insight into the early manifestations of cardiomyopathy, and help define the molecular pathophysiological basis for cardiac remodeling. Cardiovascular physicians should be fully aware of the utility and potential pitfalls of incorporating genetic test results into pre-emptive treatment strategies for patients in the preliminary stages of HF. Future work will need to be directed towards elucidating the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype-phenotype relationship. This future research should aim to further our ability to identify, diagnose, and treat disorders that cause HF and sudden cardiac death in young patients, as well as prioritize improving our ability to stratify the risk for these patients prior to the onset of the more severe consequences of their disease.

Utilities and Limitations of Cardiac Magnetic Resonance Imaging in Dilated Cardiomyopathy

Cha Min Jae,Hong Yoo Jin,Park Chan Ho,Cha Yoon Jin,Kim Tae Hoon,Kim Cherry,Park Chul Hwan 대한영상의학회 2023 Korean Journal of Radiology Vol.24 No.12

Dilated cardiomyopathy (DCM) is one of the most common types of non-ischemic cardiomyopathy. DCM is characterized by left ventricle (LV) dilatation and systolic dysfunction without coronary artery disease or abnormal loading conditions. DCM is not a single disease entity and has a complex historical background of revisions and updates to its definition because of its diverse etiology and clinical manifestations. In cases of LV dilatation and dysfunction, conditions with phenotypic overlap should be excluded before establishing a DCM diagnosis. The differential diagnoses of DCM include ischemic cardiomyopathy, valvular heart disease, burned-out hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, and non-compaction. Cardiac magnetic resonance (CMR) imaging is helpful for evaluating DCM because it provides precise measurements of cardiac size, function, mass, and tissue characterization. Comprehensive analyses using various sequences, including cine imaging, late gadolinium enhancement imaging, and T1 and T2 mapping, may help establish differential diagnoses, etiological workup, disease stratification, prognostic determination, and follow-up procedures in patients with DCM phenotypes. This article aimed to review the utilities and limitations of CMR in the diagnosis and assessment of DCM.

Dilated Cardiomyopathy in a 2 Month-Old Infant: A Severe Form of Hypocalcemia With Vitamin D Deficient Rickets

김병기,장승구,김신미,황진순,정조원 대한심장학회 2010 Korean Circulation Journal Vol.40 No.4

Dilated cardiomyopathy, which mostly has an idiopathic etiology or is caused by genetic inheritance or infection,can cause irreversible congestive heart failure. Hypocalcemia is a rare etiology of reversible dilated cardiomyopathy. Here we report the case of a two-month-old girl with congestive heart failure who was diagnosed as having dilated cardiomyopathy secondary to hypocalcemia. After calcium and vitamin D replacement therapy, the patient showed a rapid reduction in hypocalcemic tetany and a rapid recovery of left ventricular function. The cause of the hypocalcemia was vitamin D deficient rickets. She was exclusively breast-fed as an infant, and her mother had a vitamin D deficiency and was diagnosed with osteomalacia.