Classic electrocardiographic (ECG) voltage indexes have been applied to screen for left ventricular (LV) hypertrophy in hypertrophic cardiomyopathy (HC). However, it is unclear whether low ECG ...voltage reflects deteriorated electrical forces because of replacement of the myocardium by fibrotic tissues in HC. We investigated correlations between classic ECG voltage indexes (Cornell, total QRS voltage, and Sokolow-Lyon) and cardiac magnetic resonance (CMR) parameters focusing on the impact of low ECG voltage on the LV ejection fraction (LVEF) and myocardial fibrosis in HC. We studied 108 consecutive patients with HC who underwent CMR imaging with late gadolinium enhancement (LGE). Nineteen patients with complete right or left bundle branch block were excluded, leaving 89 patients for analysis (age 61.0 ± 13.9 years; 58 men). Of the 3 voltage indexes, the total QRS voltage and Sokolow-Lyon indexes were positively correlated with LVEF. For discriminating patients with end-stage HC (LVEF <50%) from patients with HC and preserved LVEF (≥50%), receiver-operating characteristic analysis revealed an excellent area under the curve of 0.87 for the total QRS voltage index and 0.90 for the Sokolow-Lyon index, whereas the area under the curve for the Cornell index was only 0.54 (p <0.01). Moreover, these 2 voltage indexes were negatively correlated with the extent of LGE-determined myocardial fibrosis when adjusted by the LV maximal wall thickness. In conclusion, low ECG voltage indexes may reflect increased myocardial fibrosis in patients with HC.
Abstract Background Although left ventricular (LV) morphology and function have been well studied in hypertrophic cardiomyopathy (HCM), few data exist regarding the right ventricle. Accordingly, we ...studied right ventricular (RV) morphology and function and their effect on cardiovascular events in HCM using cardiac magnetic resonance (CMR) imaging. Methods This retrospective study included 106 HCM patients (age 61.6 ± 14.5 years) examined using CMR imaging during January 2008 to September 2014. RV hypertrophy (RVH) was defined as RV maximal wall thickness > 5 mm. Results RVH was observed in 30 of the 106 patients (RVH group), with the remaining 76 patients assigned to the non-RVH group. The RVH group had higher brain natriuretic peptide levels (461.6 ± 699.8 pg/mL vs 225.3 ± 254.5 pg/mL; P = 0.01) and also showed a reduced RV end-diastolic volume index (43.4 ± 16.0 mL/m2 vs 56.6±15.2 mL/m2 ; P = 0.0001), in keeping with a greater LV mass index (109.1 ± 24.9 g/m2 vs 78.6 ± 23.0 g/m2 ; P < 0.0001). The RVH group was prominently associated with RV late gadolinium enhancement compared with the non-RVH group (33.3% vs 0%; P < 0.0001). After CMR imaging, 15 patients developed cardiovascular events that included admission for heart failure, ventricular tachyarrhythmia/fibrillation, stroke, and sudden cardiac death. Cox proportional hazard analysis revealed that RVH was an independent predictor of the occurrence of cardiovascular events after adjustments by sex, age, LV mass index, LV ejection fraction, and LV outflow tract obstruction (hazard ratio, 5.42; 95% confidence interval, 1.16-25.3; P = 0.03). Conclusions These results suggest that HCM patients with RVH on CMR images have a greater incidence of cardiovascular events than non-RVH patients. Further work is needed to confirm this observation and assess its clinical importance.
Eosinophils appear to be key cells in the pathogenesis of conjunctival inflammation in atopic keratoconjunctivitis (AKC). Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) ...mediates prostaglandin D2 (PGD2)-dependent migration of eosinophils. However, it is unclear whether CRTH2/PGD2-dependent eosinophil migration is upregulated in allergic diseases.
To compare the chemotactic responses of peripheral blood eosinophils to prostaglandin D2 in patients with severe AKC and healthy individuals.
We used an enzyme immunoassay system to measure PGD2 levels in tears and blood samples from healthy individuals and patients with AKC. CRTH2 expression on peripheral blood eosinophils was determined using reverse-transcriptase polymerase chain reaction (RT-PCR), flow cytometry, and an oligonucleotide array system. Chemotaxis experiments were performed using a modified Boyden chamber technique and an optical assay system.
The PGD2 concentrations were higher in tears from patients with severe AKC compared with healthy individuals. RT-PCR (severe and mild cases), flow cytometry (mild cases), and GeneChip analyses revealed a significantly higher expression of CRTH2 on peripheral blood eosinophils in patients with AKC than in healthy individuals. PGD2 and its stable metabolite 13,14-dihydro-15-keto-PGD2, a CRTH2 agonist, induced chemotaxis of eosinophils from patients with AKC; chemotaxis was significantly enhanced in eosinophils from patients with severe AKC compared with those from healthy individuals.
CRTH2 is more abundantly expressed on eosinophils from patients with AKC and promoted PGD2-dependent migration to a greater extent than in healthy individuals.
Abstract Background Occurrence of malignant ventricular tachyarrhythmias such as ventricular tachycardia and fibrillation (VT/VF) in hypertrophic cardiomyopathy (HCM) can be related to the extent of ...myocardial fibrosis. Although late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging has been used to detect myocardial fibrosis, few data exist regarding relationships between CMR-determined myocardial fibrosis and VT/VF in genotyped HCM populations. Objective We retrospectively investigated whether the extent of LGE can be increased in HCM patients with VT/VF compared to those without VT/VF in the genotyped HCM population. Methods and results We studied 35 HCM patients harboring sarcomere gene mutations ( TNNI3 = 22, MYBPC3 = 12, MYH7 = 1) who underwent both CMR imaging and 24-h ambulatory electrocardiographic monitoring. VT/VF were identified in 6 patients (2 men, mean age 55.0 years). The extent of LGE was significantly increased in patients with VT/VF ( n = 6) compared with those without VT/VF ( n = 29) (18.6 ± 14.4% vs. 8.3 ± 11.4%, p = 0.04), although the LGE extent was not an independent predictor for the occurrence of VT/VF. Applying a cut-off point ≥3.25%, episodes of VT/VF were identified with a sensitivity of 100%, specificity of 51.7%, positive predictive value of 30%, negative predictive value of 100%, and the area under the curve of 0.767 (95% confidence interval: 0.590–0.944). Conclusion These results demonstrate that myocardial fibrosis determined by CMR imaging may be increased in genotyped HCM patients with episodes of VT/VF. A further prospective study will be needed to clarify the association between the LGE extent and arrhythmic events in HCM patients harboring sarcomere gene mutations.
A SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rapidly progressing subtype of lung cancer with a poor prognosis and causes early postoperative recurrence among operable patients. In ...this study, we present a case of SMARCA4-UT with vertebral and chest wall invasion that successfully underwent conversion surgery after treatment with atezolizumab in combination with bevacizumab, paclitaxel, and carboplatin. The surgical specimen comprised SMARCA4-deficient and SMARCA2-positive adenocarcinoma, confirming intratumor heterogeneity. Gene panel analysis revealed no substantial differences in mutant gene profiles among tumors and no differences in SMARCA2 mutations. Furthermore, no recurrence occurred for 9 months after surgery. Thus, this case illustrates the possibility of multidisciplinary treatment including neoadjuvant therapy with immunotherapy and conversion surgery for SMARCA4-UT.
The CL/Fr mouse, known as a strain with spontaneous cleft lip and/or palate (CL/P), has been used as an animal model to investigate etiology in CL/P.
We examined a facial asymmetry mutant discovered ...in a CL/Fr mouse colony that was not associated with CL/P and was shown to be inheritable in subsequent generations. Facial asymmetry became apparent with postnatal growth, whereas it was not detectable at birth, and was termed "maxillary bending" (MB) based on the characteristic bending of the maxilla.
As a result of selective breeding, an 'MB line', In which MB was observed in 21.68% (67/309) in addition to CL/P in 17.80% (55/309) of the offspring, was developed in the CL/Fr colony. In mating experiments between the MB line and C57BL/6J, all F1 progeny showed the normal phenotype. MB was observed in 0.72% (1/139) of the F2 generation, and the backcross generation showed segregation of MB in 6.25% (22/352) and CL/P in 1.42% (5/352). These instances suggested the occurrence of an additional mutation in the CL/Fr mouse genome controlled by an autosomal recessive gene with low penetrance. However, since the CL/Fr mouse primarily has a developmental deficiency in the maxilla, the possibility that CL/P and MB share common etiologic factors cannot be completely ruled out.
The maxillary bending retains significance, as this mutant can serve as an animal model of abnormal facial growth. Elucidation of the etiologic relationship between MB and CL/P may provide clues to clarifying the deficiency in first branchial arch in the mouse.
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