Interação entre especialidades: miocardiopatia dilatada e neoplasia de mama HER2 positiva / Interaction between specialties: dilated cardiomyopathy and HER2-positive breast Cancer / Interacción entre especialidades: miocardiopatía dilatada y neoplasia de mama HER2 positiva

O progresso no conhecimento dos mecanismos da doença e suas potenciais possibilidades de tratamento, têm com o incremento da pesquisa básica, trazido a algumas situações inusitadas. Como quando algo observado em uma situação específica, definida na prática clínica, pode ser transportado para o laboratório, instigando a investigação de uma provável terapêutica em uma doença não relacionada e fazendo o caminho inverso da "bench-to-bedside". Nos últimos anos, o uso de um anticorpo monoclonal, o trastuzumabe, mostrou-se imprescindível no tratamento das neoplasias de mama com amplificação/superexpressão de HER2, com ganho de sobrevida significativo nos contextos adjuvante e terapêutico. A observação da ocorrência de cardiotoxicidade induzida pelo trastuzumabe, assim como a identificação dos mecanismos relacionados a esse efeito colateral, possibilitaram a pesquisa desses mesmos fatores na miocardiopatia dilatada, de uma forma muito interessante.

Basic research may result in unexpected benefit in terms of progress in the understanding of mechanisms responsible for different diseases and their potential treatment alternatives. This is seen, for instance, when a specific situation, defined in clinical practice, may be translated into laboratory findings which suggest a new therapy for an unrelated disease, representing the inverse of the more usual bench-to-bedside path. During the past few years, the use of the monoclonal antibody trastuzumab, in the adjuvant and therapeutic context, has become of fundamental importance in the treatment of breast cancer with amplification/overexpression of HER2, resulting in significant increase in survival rates. The observation that trastuzumab also induces cardiotoxicity, and the identification of mechanisms involved in this side effect, have allowed the investigation of these factors as a therapeutic alternative for dilated cardiomyopathy, in a highly interesting fashion.

El progreso en el conocimiento de los mecanismos de la enfermedad y sus potenciales posibilidades de tratamiento ocurre mediante el incremento de la investigación básica que se añade a algunas situaciones inusitadas. Así como cuando algo observado en una situación específica, definida en la práctica clínica, se puede trasladar al laboratorio, fomentando la investigación de una probable terapéutica en una enfermedad no relacionada, y haciendo el camino inverso de la "bench-to-bedside". En los últimos años, el uso de un anticuerpo monoclonal, el trastuzumabe, se halló imprescindible en el tratamiento de las neoplasias de mama con amplificación/superexpresión de HER2, con ganancia de sobrevida significativa en los contextos adyuvante y terapéutico. La observación de la ocurrencia de cardiotoxicidad inducida por el trastuzumabe, así como la identificación de los mecanismos relacionados a este efecto colateral, posibilitaran la investigación de estos mismos factores en la miocardiopatía dilatada, de una forma muy interesante.

Tachycardia Induced Cariomyopathy in Childhood

PURPOSE: Dilated cardiomyopathy in children is usually progressive and leads to death in several years. Chronic tachyarrhythmia has been shown to cause dilated cardiomyopathy in human and animals and this ventricular dysfuntion is usually reversible after control of the arrhythmia. The uncontrolled chronic tachycardia may be a curable cause of dilated cardiomyopathy in some patients. We describe six children who had persistent chronic tachycardia and ventricular dysfunction that improve significantly after control of the arrhythmia. METHODS: We retrosepctively reveiwed the medical records, electrocardiograms, Holter recordings, Echcardiographic reports of 6 children with the tachycardia induced ventricular dysfunction who have been managed at Sejong general hospital and Asan medical center from January 1992 to June 1995. RESULTS: 1) The causes of referral were dilated cardiomyopathy in 2 and tachyarrhythmia in 4. The age at diagnosis was 4 to 36 months old and follow-up period was 6 to 29 months. The symptoms of congestive heart failure were seen in 3 children. 2) The mechanisms of thachyarrhythmia causing cardiomyopathy were atrial ectopic tachycardia in 2, chaotic atrial rhythm in 3 and junctional ectopic tachycardia in 1. Atrial ectopic tachycardia has improved after combined treatment with amidarone and atenonl. One case of chaotic atrial rhythm has improved spontaneously and other 2 cases of chaotic arial rthythm have improved after treatment with digoxin or after combined therapy with amidarone and digoxin. Junctional ectopic tachycardia is partially controlled with mexiletine. 3) The shortening fractions of left ventricle at diagnosis were 14-21% and improved to over 30% in all after 2 to 9 months of follow-up. CONCLUSIONS: We have shown that control of persistent tachycardia resolved the left ventricular dysfunction. We suggest that patients with dilated cardiomyopathy be carefully screened for tachyarrhythmia as a curable cause of ventricular dysfunction and that left ventricular function be assessed in the asymptomatic patients with persistent tachycardia.

Tachycardia Induced Cariomyopathy in Childhood

PURPOSE: Dilated cardiomyopathy in children is usually progressive and leads to death in several years. Chronic tachyarrhythmia has been shown to cause dilated cardiomyopathy in human and animals and this ventricular dysfuntion is usually reversible after control of the arrhythmia. The uncontrolled chronic tachycardia may be a curable cause of dilated cardiomyopathy in some patients. We describe six children who had persistent chronic tachycardia and ventricular dysfunction that improve significantly after control of the arrhythmia. METHODS: We retrosepctively reveiwed the medical records, electrocardiograms, Holter recordings, Echcardiographic reports of 6 children with the tachycardia induced ventricular dysfunction who have been managed at Sejong general hospital and Asan medical center from January 1992 to June 1995. RESULTS: 1) The causes of referral were dilated cardiomyopathy in 2 and tachyarrhythmia in 4. The age at diagnosis was 4 to 36 months old and follow-up period was 6 to 29 months. The symptoms of congestive heart failure were seen in 3 children. 2) The mechanisms of thachyarrhythmia causing cardiomyopathy were atrial ectopic tachycardia in 2, chaotic atrial rhythm in 3 and junctional ectopic tachycardia in 1. Atrial ectopic tachycardia has improved after combined treatment with amidarone and atenonl. One case of chaotic atrial rhythm has improved spontaneously and other 2 cases of chaotic arial rthythm have improved after treatment with digoxin or after combined therapy with amidarone and digoxin. Junctional ectopic tachycardia is partially controlled with mexiletine. 3) The shortening fractions of left ventricle at diagnosis were 14-21% and improved to over 30% in all after 2 to 9 months of follow-up. CONCLUSIONS: We have shown that control of persistent tachycardia resolved the left ventricular dysfunction. We suggest that patients with dilated cardiomyopathy be carefully screened for tachyarrhythmia as a curable cause of ventricular dysfunction and that left ventricular function be assessed in the asymptomatic patients with persistent tachycardia.

Screening of the Cardiac Beta Myosin Heavy Chain Gene for the Linkage to Familial Hypertrophic Cardiomyopathy in a Korean Family

BACKGROUND: Through a genome-wide search using the genetic markers(RFLP genetic markers), the familial hypertrophic cardiomyopathy(FHCM) with an autosomal dominant mode of inheritance has been firstly detected to be genetically linked to chromosome 14q1. The subsequent studies have shown that the point mutations at the exons encoding for the head and head /rod junction of the cardiac beta myosin heavy chain(beta-MHC) are the most frequent type of mutation in the FHCM families genetically implicated with a linkage to beta-MHC, whereas the alpha/beta-MHC hybrid gene and a large deletion at the 3' region of beta-MHC gene were also rarely detected. With the other families genetically implicated with the chromosomes 1,11,15,16 and 18, FHCM also manifests locus heterogeneity, a phenomenon in which abnormalities at different genes are involved in different families. In addition, a korean FHCM family with 403Arg-->Gln mutation of beta-MHC gene has been previously found by an american research group. METHODS: For clinical diagnosis, echocardiography and electrocardiography were performed on the individual members of a korean FHCM family. The microsatellite markers(MYO-I,MYO-II) located in the beta-MHC gene region were amplified by PCR(polymerase chain reaction) and the polymorphism was analyzed for the possible linkage to the phenotypic expression of FHCM. Independently, the same PCR products of the exons 13 and 23 were digested with the specific restriction enzymes for the presence of the most frequently reported point mutations of beta-MHC gene (403 and 908 amino acid mutations). Single strand conformation polymorphism(SSCP) of the exon 13 and 23 of the beta-MHC gene was also analyzed of the mobility shift expected if any point mutation is present at these two exons. RESULTS: The inheritance pattern of HCM(hypertrophic cardiomyopathy) in the family is considered as autosomal dominant. In this family(KU 101), one of the microsatellite markers(MYO-II) indicated the possible cosegregation between the allele was also present in the 32-year-old brother of the proband, who reveals no clinical signs of the disease. The other microsatellite genetic marker(MYO-I) was uninformative, without giving the discriminating power to verify the linkage to beta-MHC gene. In the analysis for two common mutations of beta-MHC gene by PCR-RFLP and PCR-SSCP, no evidence was found for 403 and 908 amino acid mutations and any point mutation in the exons 13 and 23. CONCLUSIONS: Based on the linkage analysis using microsatellite genetic markers, there was a possibility that the disease could be linked to an abnormality in the beta-MHC gene of the chromosome 14q1.

Screening of the Cardiac Beta Myosin Heavy Chain Gene for the Linkage to Familial Hypertrophic Cardiomyopathy in a Korean Family

BACKGROUND: Through a genome-wide search using the genetic markers(RFLP genetic markers), the familial hypertrophic cardiomyopathy(FHCM) with an autosomal dominant mode of inheritance has been firstly detected to be genetically linked to chromosome 14q1. The subsequent studies have shown that the point mutations at the exons encoding for the head and head /rod junction of the cardiac beta myosin heavy chain(beta-MHC) are the most frequent type of mutation in the FHCM families genetically implicated with a linkage to beta-MHC, whereas the alpha/beta-MHC hybrid gene and a large deletion at the 3' region of beta-MHC gene were also rarely detected. With the other families genetically implicated with the chromosomes 1,11,15,16 and 18, FHCM also manifests locus heterogeneity, a phenomenon in which abnormalities at different genes are involved in different families. In addition, a korean FHCM family with 403Arg-->Gln mutation of beta-MHC gene has been previously found by an american research group. METHODS: For clinical diagnosis, echocardiography and electrocardiography were performed on the individual members of a korean FHCM family. The microsatellite markers(MYO-I,MYO-II) located in the beta-MHC gene region were amplified by PCR(polymerase chain reaction) and the polymorphism was analyzed for the possible linkage to the phenotypic expression of FHCM. Independently, the same PCR products of the exons 13 and 23 were digested with the specific restriction enzymes for the presence of the most frequently reported point mutations of beta-MHC gene (403 and 908 amino acid mutations). Single strand conformation polymorphism(SSCP) of the exon 13 and 23 of the beta-MHC gene was also analyzed of the mobility shift expected if any point mutation is present at these two exons. RESULTS: The inheritance pattern of HCM(hypertrophic cardiomyopathy) in the family is considered as autosomal dominant. In this family(KU 101), one of the microsatellite markers(MYO-II) indicated the possible cosegregation between the allele was also present in the 32-year-old brother of the proband, who reveals no clinical signs of the disease. The other microsatellite genetic marker(MYO-I) was uninformative, without giving the discriminating power to verify the linkage to beta-MHC gene. In the analysis for two common mutations of beta-MHC gene by PCR-RFLP and PCR-SSCP, no evidence was found for 403 and 908 amino acid mutations and any point mutation in the exons 13 and 23. CONCLUSIONS: Based on the linkage analysis using microsatellite genetic markers, there was a possibility that the disease could be linked to an abnormality in the beta-MHC gene of the chromosome 14q1.

Two cases of doxorubicin-induced dilated cardiomyopathy

No abstract available.

CATECHOLAMINE-INDUCED CARDIOMYOPATHY——AN ANALYSIS of 48 CASES / 中华内分泌代谢杂志

Fourty eight cases of pheochromocytoma and adrenal medullary hyperplasia confirmed by pathology were analysed. According to clinical manifestations, EKG, UCG and radiograph-ical findings, they were divided into two groups: group 1,23 cases (48.9%) without cate-cholamine-induced cardiomyopathy and group 2,25 cases (52.1%) with catecholamine-in-duced cardiomyopathy. There were no significant differences between the two groups in age, duration of disease, size and location of the pheochromocytomas. Significant differences were found in urine VMA content and types of hypertension between the two groups (P