AimsSudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure (CHF). To investigate determinants of the increased arrhythmogenic susceptibility, we studied cardiac remodelling and arrhythmogenicity in CHF patients and in a mouse model of chronic pressure overload.
Methods and resultsClinical and (immuno)histological data of myocardial biopsies from CHF patients with (VT+) and without (VT2) documented ventricular arrhythmia were compared with controls. In CHF patients, ejection fraction was decreased and QRS duration was increased. Cell size and interstitial fibrosis were increased, but Connexin43 (Cx43) levels, the most abundant gap junction in ventricular myocardium, were unchanged. No differences were found between VT+ and VT2 patients, except for the distribution pattern of Cx43, which was significantly more heterogeneous in VT+. Mice were subjected to transverse aortic constriction (TAC) or sham operated. At 16 weeks, cardiac function was determined by echocardiography and epicardial ventricular activation mapping was performed. Transverse aortic constriction mice had decreased fractional shortening and prolonged QRS duration. Right ventricular conduction velocity was reduced, and polymorphic VTs were induced in 44% TAC and 0% sham mice. Interstitial fibrosis was increased and Cx43 quantity was unchanged in TAC mice with and without arrhythmias. Similar to CHF patients, heterogeneous Cx43 distribution was significantly associated with arrhythmias in TAC mice and with spatial heterogeneity of impulse conduction.
ConclusionHeterogeneous Cx43 expression during CHF is associated with dispersed impulse conduction and may underlie enhanced susceptibility to ventricular tachyarrhythmias.--
In AAVB dogs, TdP is not spontaneously seen, whereas it is present in CAVB. This implies that ventricular remodelling is a prerequisite for TdP induction in this model.
Tropical endomyocardial fibrosis (TEMF), a restrictive cardiomyopathy of unclear etiology, is an endemic disease in equatorial Africa, South America and India. The patients are usually young, the onset of the disease and its clinical manifestations insidious, and the prognosis poor. We currently present a 50-year-old Congolese female who was referred with symptoms of progressive right-sided heart failure due to isolated TEMF of the right ventricle. Surgical resection of regional endomyocardial fibrosis was not possible and our patient was referred for cardiac transplantation. Cardiac magnetic resonance imaging (CMR) demonstrated the primary and secondary structural and functional abnormalities. CMR seems ideally suited to diagnose this condition and monitor response to medical and/or surgical therapy.
High-septal pacing reduces the magnitude of ventricular electrical remodeling and proarrhythmia in AV block dogs, suggesting a larger role for altered ventricular activation pattern in the generation of ventricular electrical remodeling than previously assumed.
Thiopental anesthesia causes arrhythmias sec, whereas anesthesia in general predisposes for drug-induced TdP in the CAVB dog. In combination with dofetilide, T + I has a more arrhythmic outcome than P + I or P + H.
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