Identifying the true origin of sustained monomorphic ventricular tachycardia associated with dilated-phase hypertrophic cardiomyopathy: A case of successful catheter ablation

AbstractThis case report describes sustained monomorphic ventricular tachycardia (VT) caused by a large epicardial scar, related to dilated-phase hypertrophic cardiomyopathy mimicking VT originating from the apical septum. VT resolved with epicardial catheter ablation. The exit of the VT circuit suggested that a 12-lead electrocardiogram can be remote with respect to the critical isthmus in this case. In patients with structural heart disease, it is difficult to identify the VT reentrant circuit by surface electrocardiography, which shows only the exit site. VT originating in the epicardium should be considered, even if the suspected origin is another ventricular site

Insufficiency of Pro-heparin-binding Epidermal Growth Factor-like Growth Factor Shedding Enhances Hypoxic Cell Death in H9c2 Cardiomyoblasts via the Activation of Caspase-3 and c-Jun N-terminal Kinase*S⃞

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a cardiogenic and cardiohypertrophic growth factor. ProHB-EGF, a product of the Hb-egf gene and the precursor of HB-EGF, is anchored to the plasma membrane. Its ectodomain region is shed by a disintegrin and metalloproteases (ADAMs) when activated by various stimulations. It has been reported that an uncleavable mutant of Hb-egf, uc-Hb-egf, produces uc-proHB-EGF, which is not cleaved by ADAMs and causes dilation of the heart in knock-in mice. This suggests that the shedding of proHB-EGF is essential for the development and survival of cardiomyocytes: however, the molecular mechanism involved has remained unclear. In this study, we investigated the relationship between uc-proHB-EGF expression and cardiomyocyte survival. Human uc-proHB-EGF was adenovirally introduced into the rat cardiomyoblast cell line H9c2, and the cells were cultured under normoxic and hypoxic conditions. Uc-proHB-EGF-expressing H9c2 cells underwent apoptosis under normoxic conditions, which distinctly increased under hypoxic conditions. Furthermore, we observed an increased Caspase-3 activity, reactive oxygen species accumulation, and an increased c-Jun N-terminal kinase (JNK) activity in the uc-proHB-EGF-expressing H9c2 cells. Treatment of the uc-proHB-EGF transfectants with inhibitors of Caspase-3, reactive oxygen species, and JNK, namely, Z-VAD-fmk, N-acetylcysteine, and SP600125, respectively, significantly reduced hypoxic cell death. These data indicate that insufficiency of proHB-EGF shedding under hypoxic stress leads to cardiomyocyte apoptosis via Caspase-3- and JNK-dependent pathways