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- Title
Diltiazem treatment prevents diastolic heart failure in mice with familial hypertrophic cardiomyopathy
- Authors
Westermann, Dirk; Knollmann, Björn C.; Steendijk, Paul; Rutschow, Susanne; Riad, Alexander; Pauschinger, Matthias; Potter, James D.; Schultheiss, Heinz-Peter; Tschöpe, Carsten
- Abstract
Abstract: Background: The cardiac troponin T I79N mutation, linked to familial hypertrophic cardiomyopathy, carries a high risk of sudden cardiac death even in the absence of significant cardiac hypertrophy. The pathology underlying this mechanism has not yet been identified. Aims: To study the underlying mechanism of this phenomenon we characterized the left ventricular (LV) performance of transgenic mice carrying the human troponin T mutation I79N under basal and isoproterenol-induced stress conditions. Methods and results: LV function was analyzed by recording pressure–volume loops using a microconductance catheter. Despite a hypercontractile systolic function under basal conditions TnT-I79N mice showed a diastolic dysfunction indicated by an increase in end-diastolic pressure–volume relationship (EDPVR), a load-independent factor of LV stiffness (0.06±0.01 vs. 0.02±0.01; P <0.05), when compared to mice expressing human wild-type troponin T (TnT-WT). TnT-I79N mutants developed severe diastolic heart failure and cardiac sudden death under isoproterenol stress. This was prevented after pretreatment with the L-type Ca2+ channel inhibitor diltiazem. Conclusions: Diastolic dysfunction due to increased LV stiffness in TnT-I79N mice leads to severe primary diastolic heart failure and finally to cardiac sudden death, which can be prevented by diltiazem.
- Subjects
CARDIOMYOPATHIES; HEART failure treatment; HYPERTROPHY; LEFT heart ventricle; CATHETERS
- Publication
European Journal of Heart Failure, 2006, Vol 8, Issue 2, p115
- ISSN
1388-9842
- Publication type
Article
- DOI
10.1016/j.ejheart.2005.07.012