HISTOPATHOLOGICAL ANALYSIS OF SURGICALLY RESECTED MYOCARDIUM IN PATIENTS WITH SUSTAINED VENTRICULAR TACHYCARDIA

Surgical resection of the endocardium and subendocardium often abolishes sustained ventricular tachycardia (VT) in patients with old myocarcial infarct (OMI), unknown myocardial disease, and arrhythmogenic right ventricular dysplasia (ARVD), presumably by interrupting the reentrant pathway. In order to define the morphologic characteristics of histologic components in the reentrant pathway, we carried out histopathological analysis of surgically resected specimens from 17 patients who underwent this procedure. Bundles of apparently viable and hydropic myocardial fibers embedded in dense fibrous and adipose tissues were identified throughout the specimens obtained from OMI, ARVD and idiopathic VT cases. In 3 patients with Idiopathic VT, most of the resected areas were composed of ventricular muscle, the components of which appeared histologically similar to Purkinje fibres. In all patients, the abnormal muscle cells were characterized by a loss of contractile elements, hydropic cytoplasm and an elliptic shape. Such an abnormal structure and arrangement of surviving cardiac fibers following tissue injury might play an important role in creating abnormalities of transmembrane potential, leading to the micro-reentrant circuits that give rise to ventricular tachycardias.     

Partial Left Ventriculectomy in Patients with Dilated Failing Ventricle

BACKGROUND: While partial left ventriculectomy (PLV) improves left ventricular energetic efficiency, concomitant reduction in mitral regurgitation may improve ventricular function. METHODS: Two hundred ninety-five patients undergoing lateral ventricular wall excision between the papillary muscles (lateral PLV) and 101 patients with an additional excision of papillary muscles and mitral valve replacement (extended PLV) were compared with 65 patients undergoing excision of anterior wall or ventricular aneurysm (anterior PLV). RESULTS: All patients had reduced functional capacity, New York Heart Association (NYHA) Class III to IV (3.62+/-0.49). Etiologies were cardiomyopathy (37.3%), coronary artery disease (32.3%), valvular disease (19.7%), Chagas' disease (7.8%), and others (2.8%). Patients undergoing lateral and extended PLV had cardiomyopathy as the primary cause of heart failure, while a majority of anterior PLV patients had ischemic disease. Associated procedures included mitral valvuloplasty or replacement (lateral PLV 67%, extended PLV 100%, anterior PLV 40%) and tricuspid annuloplasty (67%, 76%, 28%, respectively.) In each group after surgery, end-systolic dimension decreased more than end-diastolic dimension despite reduced mitral regurgitation. Although extended PLV resulted in greater volume reduction and less mitral regurgitation, these patients had delayed recovery and poor survival. Patients with valvular disease had the most advanced myocardial hypertrophy with the best survival, while those with Chagas' disease had more severe myocarditis, interstitial fibrosis, and the poorest survival. CONCLUSION: Lateral PLV improved hemodynamics and functional capacity as much as aneurysmectomy by reducing ventricular volume and mitral regurgitation. Inclusion and exclusion criteria have to be sought to make PLV safer and more effective.     

E variants found in Japanese and c antigenicity alteration without substitution in the second extracellular loop

BACKGROUND: The molecular basis of E variants in the Japanese population is poorly understood. In this study, molecular analysis of E variants detected in Japanese by serologic methods was carried out. STUDY DESIGN AND METHODS: E variants from healthy Japanese blood donors were screened by serologic analysis using E MoAbs. Fifteen E variant samples were divided into three types--EFM, EKH, and EKK-on the basis of patterns of reactivity with five distinct E antibodies. The entire coding region of the Rh cDNAs from the E variant samples was analyzed by sequencing. RESULTS: Although the Rh cDNA sequences of the three types were different from each other, those of the EFM-type variants (RHEFM) had a partial DNA exchange in exon 5 between the RHCE and RHD genes, generating an RHcE variant (Gln233Glu, Met238Val). The cDNA of EKH-type variants (RHEKH) exhibited a point mutation (G461C) in exon 3 of the RHcE allele that resulted in an Arg154Thr substitution in the third external loop of the RhcE peptide. The EKK-type variant (RHEKK) carried a hybrid gene structure characterized by replacement of exons 1-3 (or 2-3) of the RHCE gene with those of the RHD gene. The RHD gene of a person possessing an E variant of the EKK type was also a hybrid gene, D-cE(2-3)-D or cE(1-3)-D (RHDKK). The E variants of types EKH and EKK showed weak c antigenicity. CONCLUSION: In serologic screening of 140,723 Japanese blood donors, 15 were found to possess E variants (0.011%). A new RHCE variant, RHEKH, was identified. On the basis of the variants found in this study, the c antigenicity seemed to be determined not only by Pro-103 but also by the structure of the third extracellular loop or the amino acids contained in it.     

Löffler's endocarditis associated with unusual ECG change mimicking posterior myocardial infarction

A73-year-old man with a history of bronchial asthma and atrial fibrillation was admitted to our hospital because of dyspnea and back pain. Blood analysis revealed a marked increase in total blood cell and eosinophil counts. The creatine kinase and creatine kinase-MB increased slightly. The ECG demonstrated significant ST-segment depression that mimicked acute posterior myocardial infarction. Emergent coronary angiography showed no stenotic lesions. The histological findings in endomyocardial biopsy showed thickened endocardium associated with significant eosinophilic infiltration, which was compatible with L?ffler's endocarditis. After the administration of prednisolone, the patient's general condition, eosinophilia, ECG abnormalities, and histological findings were improved dramatically. The endomyocardial biopsy in the acute phase was helpful for diagnosis and therapeutic decision-making.     

Distribution of myofibroblast and tenascin‐C in cystic adventitial disease: Comparison with ganglion

Cystic adventitial disease (CAD) is a rare peripheral artery disorder which shows the development of gelatinous cysts in the adventitia. Although several theories for the pathogenesis of CAD have been postulated, the etiology of CAD remains unclear. Histological examination of three CAD cases revealed that these cyst walls were composed of fibrous tissue and lacked both epithelial and endothelial lining. The surfaces of these cysts were partially covered with spindle‐shaped cells, similar to the interstitial cells within the cyst wall. A pool of mucinous material in the adventitia was evident. Distribution of vimentin‐positive spindle‐shaped cells and scattered CD68‐positive oval‐shaped cells in the cyst wall was revealed by immunohistochemistry. A part of vimentin‐positive spindle‐shaped cells demonstrated to be positive for α‐smooth muscle actin, indicating the presence of myofibroblasts in the cyst wall. A focal tenascin‐C‐positive area was observed in the cyst wall of our CAD cases. Presence of two different cell types, proliferation of myofibroblasts and expression of tenascin‐C were consistent with those of cyst walls of 20 surgically resected ganglions. These results suggest that CAD may arise as capsular synovial structures, similar to ganglion cysts.     

Ribavirin induces hepatitis C virus genome mutations in chronic hepatitis patients who failed to respond to prior daclatasvir plus asunaprevir therapy

Ribavirin (RBV) induces nucleotide (nt) substitutions in hepatitis C virus (HCV) genome nonstructural (NS) regions. Although emergence of drug resistance-associated variants is associated with direct-acting antiviral treatment failure, the effect of RBV on genome substitutions in such patients is unknown. Genotype 1b HCV subgenomic replicon cells were treated with RBV for 120 hours. Six patients with chronic genotype 1b with HCV-infected patients who failed to respond to prior daclatasvir plus asunaprevir (DCV/ASV) therapy were treated with 12 weeks of sofosbuvir and ledipasvir plus RBV after 4 weeks of RBV monotherapy. RBV-induced genome mutations in the HCV NS region (nt3493-9301) in replicon cells and in patients during 4 weeks of RBV monotherapy were analyzed by deep sequencing. RBV-associated G-to-A and C-to-U transitions increased in a dose-dependent manner in HCV replicon cells after the RBV treatment. In patients with prior DCV/ASV treatment failures, the median serum HCV RNA level was 6.25 ± 0.31 log IU/mL at the start of RBV therapy and decreased significantly to 5.95 ± 0.4 log IU/mL (P = .03) after 4 weeks of RBV monotherapy. Although predominant HCV genome substitutions rates were similar between nontreatment and RBV-treatment periods (0.042 and 0.031 per base pair, respectively; P = .248), the frequencies of G-to-A and C-to-U transitions significantly increased after RBV monotherapy. These transitions were enriched, particularly within the HCV NS3 region in all patients. RBV treatment induces G-to-A and C-to-U transitions in the HCV genome even in chronic patients with hepatitis C with prior DCV/ASV treatment failures.     

Steroid-refractory chronic idiopathic thrombocytopenic purpura associated with hepatitis C virus infection

OBJECTIVES: Hepatitis C virus infection has often been suggested as a possible cause of various kinds of autoimmune diseases. The aim of this study was to determine the relationship between chronic idiopathic thrombocytopenic purpura (ITP) and hepatitis C virus infection and to characterize the clinical features of anti-HCV antibody (HCVab) positive chronic ITP patients. SUBJECTS AND METHODS: We studied HCVab in 79 patients with chronic ITP (25 males, 54 females, mean age 42.3 yr, range 11-86 yr) using the third-generation ELISA method. RESULTS: HCVab was detected in 11 of the 79 patients (13.9%). Quantitative HCV-RNA studies showed a high serum concentration of HCV-RNA in these patients. The platelet counts in these 11 HCVab-positive patients (Group 1) were lower than in the 68 HCVab-negative patients (Group 2) [(2.6 +/- 0.9) versus (4.9 +/- 3.0) x 10(10)/L, respectively; p<0.02]. Significantly more patients in Group 1 required prednisolone therapy (10/11, 90.9%) than in Group 2 (31/68, 45.6%) (P < 0.005). The response rate to prednisolone treatment was significantly higher in Group 2 (19/31, 61.3%) than in Group 1(0/10, 0%) (P < 0.001). There was no difference in the response to splenectomy between Groups 1 (4/7, 57.1%) and 2 (3/5, 60%). CONCLUSION: Given these findings, we recommend that HCVab is measured upon diagnosis of chronic ITP, and that splenectomy is planned in patients with HCVab in the event that prednisolone treatment is ineffective.