Anti-mitochondrial flavoprotein autoantibodies of patients with myocarditis and dilated cardiomyopathy (anti-M7): interaction with flavin-carrying proteins, effect of vitamin B2 and epitope mapping

Vitamin B2 and flavin cofactors are transported tightly bound to immunoglobulin in human serum. We reasoned that anti-mitochondrial flavoprotein autoantibodies (alpha Fp-AB) present in the serum of patients with myocarditis and cardiomyopathy of unknown aetiology may form immunoglobulin aggregates with these serum proteins. However, immunodiffusion and Western blot assays demonstrated that the flavin-carrying proteins were not recognized by alpha Fp-AB. Apparently the flavin moiety in the native protein conformation was inaccessible to alpha Fp-AB. This conclusion was supported by the absence of an immunoreaction between the riboflavin-binding protein from egg white and alpha FP-AB. Intravenous application of vitamin B2 to rabbits immunized with 6-hydroxy-D-nicotine oxidase, a bacterial protein carrying covalently attached FAD, did not neutralize alpha Fp-AB which had been raised in the serum of the animals. FAD-carrying peptides generated from 6-hydroxy-D-nicotine oxidase by trypsin and chymotrypsin treatment were not recognized by the alpha Fp-AB, but those generated by endopeptidase Lys were. This demonstrates that the epitope recognized by alpha Fp-AB comprises, besides the flavin moiety, protein secondary structure elements.     

Myocarditis: unresolved issues in diagnosis and treatment

Myocarditis is an enigmatic disease. Lymphocytic myocarditis is most commonly viral in origin. Considerable evidence suggests that myocardial damage is due to an immune-mediated mechanism rather than to direct effects of the virus itself. The presentation is variable, ranging from a clinically inapparent or relatively benign illness to acute progressive heart failure and death. Although examination of the endomyocardial biopsy specimen is the "gold standard" for the diagnosis of myocarditis there are problems with this technique, relating particularly to sampling error and histologic interpretation. Considerable evidence, both animal and human, suggests that a link between viral myocarditis and dilated cardiomyopathy does exist. There is a rational basis for the use of immunosuppressive therapy in myocarditis. Although many favorable responses have been reported with the use of these agents, the results of more definitive studies are awaited to determine the role of immunosuppressive therapy in myocarditis more clearly. Recommendations for the practical management of patients with myocarditis are made. Whenever possible, patients with this diagnosis should be entered into the ongoing NIH trial.     

QT Dispersion Level and Its Clinical Significance.in Dilated Cardiomyopathy

［1］Richardson CP, Mckenna RM, Bristow CM, et al.Report of the 1995 Word Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation, 1996,93: 841 ［2］Barr CS, Naas A, Freeman M, et al. QT dispersion and sudden unexpected death in chronic heart failure. Lancet, 1994,343:327 ［3］Martin AB, Garson A, Perry JC, et al. Prolonged QT interval in hypertropic and dilated cardiomyopathy in children. Am Heart J, 1994,127(1):64 ［4］Pye M, Quinn AC, Cobble SM. QT dispersion: a non-invasive marker of susceptibility to arrhythmia in patients with sustained ventricular arrhythmias?Br Heart J, 1994,71(5):51 ［5］Berger RD, Kasper EK, Baughman KL, et al. Beat to beat QT interval variability: novel evidence for repolarization lability in ischemic and non ischemic dilated cardiomyopathy. Circulation, 1997, 96 (5):1557 ［6］Wolfram G, Ulrike S, Volker M, et al. QT dispersion and arrhythmic events in idiopathic dilated cardiomyopathy. Am J Cardiol, 1997,78: 458 ［7］Fei L, Goldman JH, Prasal K, et al. QT dispersion and RR variations on 12-lead ECGs in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy. Eur Heart J, 1996,17: 258 ［8］Pan YZ, Guo NS, Xing ZF, et al. The relation between QT dispersion and ventricular arrhythmia of dilated cardiomyopathy. Chin J Inter Medi, 1996,35(11):73 ［9］Galinier M, Vialette JC, Fourcade J, et al. QT interval dispersion as a predictor of arrhythmic events in congestive heart failure. Importance of aetiology. Eur Heart J, 1998,19(7) :1054     

超声心动图对扩张性心肌病患者左室舒张功能的评价

为评价超声心动图对扩张性心肌病（ＤＣＭ）患者左室舒张功能的诊断价值。方法：用超声心动图 和放射性核素显像（ＲＮＶ）对２０例ＤＣＭ患者和２０例同龄正常人的左室舒张功能进行对照分析。结果：ＤＣＭ组左室 舒张功能ＲＮＶ指标峰充盈率（ＰＦＲ）明显降低,同对照组比较差异有显著性（Ｐ＜０．０５）;超声指标二尖瓣血流频谱早 期充盈峰速度（νＥ）、晚期充盈峰速度（νＡ）、νＡ／νＥ等参数同对照组比较无明显差异（Ｐ＞０．０５）,表现为“正常”。结 论：超声心动图舒张功能指标νＥ、νＡ、νＡ／νＥ不能真实反映ＤＣＭ患者的左室舒张功能。     

美托洛尔治疗充血性心力衰竭的临床研究

目的：探讨美托洛尔（ｍｅｔｏｐｒｏｌｏｌ）治疗充血性心力衰竭（ＣＨＦ）的有效性和可行性。方法：采用随机对照方法,观察经强心、利尿和血管紧张素转换酶抑制剂（ＡＣＥＩ）治疗仍有ＣＨＦ症状的扩张型心肌病患者加用美托洛尔治疗前后循环内分泌因子和心功能状态的变化。结果：①治疗３个月时,美托洛尔组心胸比和心脏面积与对照组相比均明显缩小（分别Ｐ＜００１）;②治疗３个月时,美托洛尔组左室射血分数（ＬＶＥＦ）较对照组显著增高（３７３５±６２８ｖｓ３３２５±６４６,Ｐ＜００１）;③所有患者血浆内皮素（ＥＴ）和去甲肾上腺素（ＮＥ）水平均与ＬＶＥＦ呈负相关（均Ｐ＜０００１）;④显效组患者年龄偏小,心率偏快,血浆ＮＥ,ＥＴ水平较高,和其他组相比有显著差异。结论：美托洛尔治疗ＣＨＦ有效,尤其年龄偏小、心率偏快、血浆ＮＥ和ＥＴ水平较高的扩张型心肌病亚组。     

玻璃体腔注药有必要散瞳吗?

玻璃体腔注药是目前眼科最常用的治疗手段之一,操作简单,手术时间较短。但是对于注药前是否有必要进行散瞳国内尚未达成共识,为此我们进行了一项网络问卷调查,在参阅国外相关研究的基础上,就上述问题进行了讨论并提出我们的主张,玻璃体腔注药术前常规散瞳没有必要。     

Phospholamban p.Arg14del Cardiomyopathy: A Japanese Case Series

Phospholamban p.Arg14del is reported to cause hereditary cardiomyopathy with malignant ventricular tachycardia (VT) and advanced heart failure. However, the clinical courses of Japanese cardiomyopathy patients with phospholamban p.Arg14del remain uncharacterized. We identified five patients with this variant. All patients were diagnosed with dilated cardiomyopathy (DCM), developed end-stage heart failure and experienced VT requiring implantable cardioverter defibrillator discharge. Four patients survived after implantation of a left ventricular assist device (LVAD), while one patient who refused LVAD implantation died of heart failure. Based on the severe course of the disease, we propose genetic screening for phospholamban p.Arg14del in DCM patients.     

Regional distribution of β1- and β2-adrenoceptors in the failing and nonfailing human heart

Summary Total -adrenoceptor density and ₁- and ₂-subtype distribution in right and left atria and in different ventricular regions from 14 failing and seven nonfailing human hearts have been compared. End-stage heart failure was due to idiopathic dilated cardiomyopathy (n=8) or ischaemic cardiomyopathy (n=6).In nonfailing hearts the total -adrenoceptor density was similar in the right and left atria and in all the ventricular regions studied (about 70 to 80 fmol/mg protein). The ₁:₂-adrenoceptor ratio in both nonfailing atria was similar (about 70:30%) and was significantly smaller than in the different regions of both ventricles (about 80:20%). The ₁-subtype density was similar in nonfailing atria and ventricles (about 55 fmol/mg protein). The ₂-subtype density was significantly higher in the right and left atrium (about 25 fmol/mg protein) than in both ventricles (about 15 fmol/mg protein).In patients with end-stage heart failure due to idiopathic dilated cardiomyopathy or ischaemic cardiomyopathy the total -adrenoceptor density was reduced by 50–60% in all regions. On the other hand, the ₁- and ₂-subtype distribution differed with the cause of heart failure. In patients with idiopathic dilated cardiomyopathy, the ₁-adrenoceptor density was lower in all regions, but the ₂-adrenoceptor density was not significantly reduced. In patients with ischaemic cardiomyopathy both ₁- and ₂-adrenoceptors were reduced in all regions.It is concluded that downregulation of -adrenoceptors in patients with end-stage idiopathic dilated cardiomyopathy or ischaemic cardiomyopathy occurs uniformly throughout the heart. The results support the hypothesis that changes in -adrenoceptor subtypes may be related to the cause of heart failure.     

Electrocardiographic and Echocardiographic Features That Distinguish Anomalous Origin of the Left Coronary Artery from Pulmonary Artery from Idiopathic Dilated Cardiomyopathy

Many authors have reported noninvasive means of diagnosing anomalous left coronary artery from pulmonary artery (ALCAPA) and differentiating ALCAPA from idiopathic dilated cardiomyopathy (DCM). Systematic evaluation using these noninvasive diagnostic modalities is not available. To distinguish between ALCAPA and DCM using a systematic approach, we examined 23 patients with ALCAPA (age 1 month to 23 years, median 7 months) and 23 patients with DCM (age 5 days to 16 years, median 6.6 months). Standard 12-lead electrocardiograms (ECG) and 2-dimensional (2-D) and color Doppler echocardiograms were performed. A logistic regression model was applied using ALCAPA diagnosis as the dependent variable and ECG and echocardiographic findings as independent variables. A scoring system was created to establish the ALCAPA diagnosis based on results from the logistic regression. On the logistic regression, the ECG feature of QT pattern in aVL (Q wave ≥ 3 mm deep with an inverted T wave) and echocardiographic features of right coronary artery diameter to aortic annulus ratio ≥ 0.14, increased papillary muscle echogenicity, and Doppler color flow of LCA from aorta or pulmonary artery were the most significant differentiating features between the ALCAPA and DCM groups. A scoring system was developed using the previous five variables and assigning a score of 1 to each variable (−1 to Doppler color flow of LCA from aorta). The scoring system had sensitivity of 100% and specificity of 91% for ALCAPA diagnosis. Compared with previous reported diagnostic features in differentiating ALCAPA and DCM, the scoring system had a much higher specificity and positive predictive value. In conclusion, we selected the most useful ECG and echocardiographic features to differentiate between ALCAPA and DCM and created a scoring system to aid clinical diagnosis. This scoring system may be useful in evaluating children with acute congestive heart failure.     

Recovery of complete left bundle branch block in a dilated cardiomyopathy patient after treatment with sacubitril/valsartan: A case report

Rationale:The treatment of dilated cardiomyopathy (DCM) has recently been greatly improved, especially with the widespread use of sacubitril/valsartan (ARNI) combination therapy. We know that ARNI-like drugs can significantly improve the symptoms of heart failure with reducing ejection fraction. However, clinical studies evaluating the safety and efficacy of ARNI in DCM-associated arrhythmia are limited, and whether individuals with arrhythmia would benefit from ARNI remains controversial. In this case, we report a patient with complete left bundle branch block (CLBBB) associated with DCM whose CLBBB returned to normal after treatment with ARNI.Patient concerns:A 38-year-old man was admitted to the hospital for 20 days for idiopathic paroxysmal dyspnea. He presented with exacerbated dyspnea symptoms at night, accompanied by cough and sputum.Diagnosis:Physical examination revealed a grade 4/6 systolic murmur could be heard in the apical area of the heart and mild edema was present in both lower limbs. Laboratory examination found that the B-type natriuretic peptide was significantly increased. Echocardiography indicated left atrial internal diameter, right ventricular internal diameter, and left ventricular diastolic diameter were enlarged and ejection fraction was significantly decreased. Besides, the pulsation of the wall was diffusely attenuated. Electrocardiogram was suggestive of tachycardia and CLBBB. A diagnosis of DCM with CLBBB was considered based on a comprehensive evaluation of the physical examination, laboratory examination, echocardiography and electrocardiogram.Interventions:The patient was treated with ARNI at a dose of 50 mg (twice a day) at first, gradually increasing to the target dose (200 mg, twice a day) in the following 9 months as shown in Table ​Table1,1, along with metoprolol 25 mg (once a day [qd]), diuretics 20 mg (qd), and aldosterone 20 mg (qd).Table 1Specific medications used in treatment.