Presence Of VT Research Articles

Extracellular volume is an independent predictor of arrhythmic burden in dilated cardiomyopathy

The current stratification of arrhythmic risk in dilated cardiomyopathy (DCM) is sub-optimal. Cardiac fibrosis is involved in the pathology of arrhythmias; however, the relationship between cardiovascular magnetic resonance (CMR) derived extracellular volume (ECV) and arrhythmic burden (AB) in DCM is unknown. This study sought to evaluate the presence and extent of replacement and interstitial fibrosis in DCM and to compare the degree of fibrosis between DCM patients with and without AB. This is a prospective, single-center, observational study. Between May 2019 and September 2020, 102 DCM patients underwent CMR T1 mapping. 99 DCM patients (88 male, mean age 45.2 ± 11.8 years, mean EF 29.7 ± 10%) composed study population. AB was defined as the presence of VT or a high burden of PVCs. There were 41 (41.4%) patients with AB and 58 (58.6%) without AB. Replacement fibrosis was assessed with late gadolinium enhancement (LGE), whereas interstitial fibrosis with ECV. Overall, LGE was identified in 41% of patients. There was a similar distribution of LGE (without AB 50% vs. with AB 53.7%; p = 0.8) and LGE extent (without AB 4.36 ± 5.77% vs. with AB 4.68 ± 3.98%; p = 0.27) in both groups. ECV at nearly all myocardial segments and a global ECV were higher in patients with AB (global ECV: 27.9 ± 4.9 vs. 30.3 ± 4.2; p < 0.02). Only indexed left ventricular end-diastolic diameter (HR 1.1, 95%CI 1.0–1.2; p < 0.02) and global ECV (HR 1.12, 95%CI 1.0–1.25; p < 0.02) were independently associated with AB. The global ECV cut-off value of 31.05% differentiated both groups (AUC 0.713; 95%CI 0.598–0.827; p < 0.001). Neither qualitative nor quantitative LGE-based assessment of replacement fibrosis allowed for the stratification of DCM patients into low or high AB. Interstitial fibrosis, expressed as ECV, was an independent predictor of AB in DCM. Incorporation of CMR parametric indices into decision-making processes may improve arrhythmic risk stratification in DCM.

Metavinculin Tunes the Flexibility and the Architecture of Vinculin-Induced Bundles of Actin Filaments

Vinculin is an abundant protein found at cell–cell and cell–extracellular matrix junctions. In muscles, a longer splice isoform of vinculin, metavinculin, is also expressed. The metavinculin-specific insert is part of the C-terminal tail domain, the actin-binding site of both isoforms. Mutations in the metavinculin-specific insert are linked to heart disease such as dilated cardiomyopathies. Vinculin tail domain (VT) both binds and bundles actin filaments. Metavinculin tail domain (MVT) binds actin filaments in a similar orientation but does not bundle filaments. Recently, MVT was reported to sever actin filaments. In this work, we asked how MVT influences F-actin alone or in combination with VT. Cosedimentation and limited proteolysis experiments indicated a similar actin binding affinity and mode for both VT and MVT. In real-time total internal reflection fluorescence microscopy experiments, MVT's severing activity was negligible. Instead, we found that MVT binding caused a 2-fold reduction in F-actin's bending persistence length and increased susceptibility to breakage. Using mutagenesis and site-directed labeling with fluorescence probes, we determined that MVT alters actin interprotomer contacts and dynamics, which presumably reflect the observed changes in bending persistence length. Finally, we found that MVT decreases the density and thickness of actin filament bundles generated by VT. Altogether, our data suggest that MVT alters actin filament flexibility and tunes filament organization in the presence of VT. Both of these activities are potentially important for muscle cell function. Perhaps MVT allows the load of muscle contraction to act as a signal to reorganize actin filaments.

Predicting utility of exercise tests based on history/holter in patients with premature ventricular contractions.

Premature ventricular contractions (PVCs) are considered benign in patients with structurally normal hearts, particularly if they suppress with exercise. Catecholaminergic polymorphic ventricular tachycardia (CPVT) requires exercise testing to unmask the malignant phenotype. We studied risk factors and Holter monitor variables to help predict the necessity of exercise testing in patients with PVCs. We retrospectively reviewed 81 patients with PVCs that suppressed at peak exercise and structurally normal hearts referred to the exercise laboratory in 2011. We reviewed 11 patients from 2003 to 2012 whose PVCs were augmented at peak exercise (mean age 13±4years; 52% male, 180 exercise studies). We recorded clinical risk factors and comorbidities (family history of arrhythmia or sudden unexpected death [SUD], presence of syncope) and Holter testing parameters. Family history of VT or SUD (P=0.011) and presence of VT on Holter (P=0.011) were significant in predicting failure of PVCs to suppress at peak heart rate on exercise testing. Syncope was not statistically significant in predicting suppression (P=0.18); however, CPVT was diagnosed in four patients with syncope during exercise. Quantity of PVCs, Lown grade, couplets on Holter, monomorphism, and PVC elimination at peak heart rate on Holter were not predictors of PVC suppression on exercise testing. Patients with syncope during exercise, family history of arrhythmia or SUD, or a Holter monitor showing VT warrant exercise testing to assess for CPVT.

Electrocardiographic abnormalities and arrhythmias are strongly associated with the development of cardiomyopathy in muscular dystrophy

Dilated cardiomyopathy (DCM) is a well-recognized sequela of muscular dystrophy (MD). Early identification of cardiac involvement with timely therapy can favorably impact outcome. We hypothesize that electrocardiography (ECG) can be a useful adjunct in the identification of DCM in MD. This study sought to assess the utility of electrocardiography in patients with MD. A retrospective review of patients with MD was performed. ECGs and Holter monitor results were analyzed to assess for association between abnormalities and the development of DCM. This study identified 150 patients. In 43% of patients (64 of 150) DCM developed. ECG abnormalities were found in 65% of patients and correlated well with the presence of DCM, with 60 of 64 (94%) with DCM having an abnormal ECG vs. 38 of 86 (44%) without DCM (P < .001). Only 4 of 52 (8%) of patients with normal ECGs had DCM. The presence of ECG abnormalities was highly sensitive (95.8%) but not specific (40.1%) to the presence of DCM. ECG abnormalities often preceded the development of DCM by a significant period of time (3.7 ± 2.6 years). Arrhythmias were common, with 17 of 150 (11%) of the cohort being affected. Those with DCM were significantly more likely to have an arrhythmia, with 16 of 64 (25%) of that group being affected (P < .01). The presence of VT was a poor prognostic indicator, with 6 of 11 patients dying within 0.68 ± 0.41 years. ECG abnormalities are strongly associated with DCM in patients with MD and frequently precede cardiac dysfunction by several years. Arrhythmias are common, and periodic ECG and Holter evaluations are warranted as they may predict early cardiac involvement.

Effects of 4‐nonylphenol on the endocrine system of the shore crab, Carcinus maenas

There is a considerable body of evidence to suggest that many anthropogenic chemicals, most notably xeno-estrogens, are able to disrupt the endocrine system of vertebrates. There have been few comparable studies on the effects of exposure to these chemicals that may serve as biomarkers of endocrine disruption in aquatic invertebrate species. In addition, the evidence available is complex, conflicting, and far from conclusive. The present study aimed to investigate the impact of the xeno-estrogen 4-nonylphenol (4-NP, nominal concentrations 10-100 microg L(-1)) on the regulation and functioning of the endocrine system of the shore crab Carcinus maenas. It also set out to establish whether 4-NP are causing the effects (i.e., changes of exoskeletons including secondary sexual characteristics, pheromonally mediated behavior and ecdysone levels, and the presence of vt in the male hepatopancreas) found recently in wild shore crabs (Lye et al.,2005). The study utilizes morphological (e.g., gonadosomatic and hepatosomatic indices) and hormonal (ecdysteroid moulting hormone levels and the induction of female specific proteins, vitellins) biomarkers using radioimmunoassay and an indirect enzyme linked immunosorbent assay applied to the soluble protein fraction of adult male hepatopancreatic homogenates. Exposure of C. maenas to an effective concentration as low as 1.5 microg L(-1) 4-NP resulted in a reduced testis weight, increased liver weight, and altered levels of ecdysone equivalents compared to controls. Induction of vitellin-like proteins was absent in all samples tested. The ecological implications and the possible mechanisms for the action of 4-NP on the response of the shore crab to xeno-estrogen exposure are discussed.

Effects of trichothecene structure on cytokine secretion and gene expression in murine CD4 + T-cells

The effects of trichothecene structure on cytokine secretion and gene expression were assessed in primary CD4 + T-cells from murine spleen. CD4 + T-cells were stimulated with concanavalin A (Con A) for 2 or 7 days in the presence of various concentrations of the trichothecenes, vomitoxin (VT or deoxynivalenol), nivalenol (NIV), 15-acetyl deoxynivalenol (15-ADON), 3-acetyl deoxynivalenol (3-ADON), T-2 toxin (T-2) and verrucarin A (Ver A). Culture supernatants were subsequently analyzed for interleukin (IL)-2, IL-4 and IL-5 by ELISA. At day 2, all trichothecenes were found to have inhibited production of IL-2, IL-4, and IL-S. However, at day 7, supernatant IL-2 was significantly increased (2–5.5-fold) in cultures containing VT, NIV, 3-ADON, and 15-ADON at 250, 250, 2500, and 1000 ng/ml doses, respectively, when compared to control Con A-stimulated cultures; significant increases in IL-2 were not observed with T-2 and Ver-A. Similarly, at day 7, IL-4 and IL-5 were significantly increased in the presence of VT (100 ng/ml), NIV (100 ng/ml), 3-ADON (1000 ng/ml), 15-ADON (500 ng/ml), T-2 (1 ng/ml), and Ver A (50 pg/ml, only IL-5) when compared to control cultures. IL production was inhibited at trichothecene concentrations exceeding the aforementioned optima. When total RNA of 2-day cultures was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) in conjunction with Southern analysis, IL-2 mRNA was also found to be superinduced by VT (50 and 100 ng/ml), NIV (50, 100 and 250 ng/ml), 3-ADON (1500 ng/ml), 15-ADON (100 ng/ml), T-2 (0.5 ng/ml) and Ver A (25, 50 and 100 pg/ml); IL-4 mRNA by VT (50 ng/ml), NIV (50 ng/ml), and Ver A (25, 50 and 100 pg/ml); IL-5 mRNA by VT (50 ng/ml); and IL-6 mRNA by 15-ADON (100 ng/ml) and Ver A (50 pg/ml). As the trichothecene concentration increased from these levels, inhibition of mRNA transcript levels was also observed for many of the interleukins. Taken together, the results suggest that trichothecenes as a group can either inhibit or superinduce both IL secretion and mRNA levels in CD4 + T-cells. Superinduction exhibited a rank order of macrocyclic > type A > type B trichothecenes and was dependent on acylation of the trichothecene nucleus.