title: Failure of myocardial inactivation: a clinical assessment in the hypertrophied heart.
abstract: BACKGROUND
  Abnormal intracellular calcium handling is observed in hypertrophied cardiac muscle and in end-stage heart failure muscle. This abnormal calcium handling results in prolongation of the calcium transient and in a biphasic calcium transient with prominent late component. In the present studies, the mechanical correlates of abnormal calcium handling were investigated in the hypertrophied human left ventricle by analysis of: 1) isovolumic left-ventricular relaxation kinetics after drastic left-ventricular unloading in patients with severe aortic stenosis after sequential balloon aortic valvuloplasty-arterial vasodilation; and 2) morphology of the diastolic left-ventricular pressure signal in patients with aortic stenosis and hypertrophic cardiomyopathy.
  
  
  RESULTS
  Drastic left-ventricular unloading in patients with severe aortic stenosis by sequential aortic valvuloplasty-arterial vasodilation resulted in a slow and dyssynchronous left-ventricular relaxation pattern, as evident from a prolongation of the time constant of left-ventricular pressure decay from 46.6 +/- 12.5 to 73.2 +/- 23.3 ms (p < 0.01), and from the development of a convex downward negative dP/dt upstroke pattern. Abnormal diastolic left-ventricular pressure wave forms consisting of continuous left-ventricular pressure decay throughout diastole and/or a secondary pressure rise in mid-diastole were observed in patients with aortic stenosis and with hypertrophic cardiomyopathy. Postextrasystolic potentiation caused further slowing of this abnormal diastolic left-ventricular pressure decay, as evident from the decrease in phase of the first harmonic of a Fourier transform applied to the diastolic left-ventricular pressure wave. When an abnormal diastolic left-ventricular pressure wave form was observed at rest or after postextrasystolic potentiation, a simultaneously recorded left-ventricular monophasic action potential signal revealed the occurrence of delayed afterdepolarizations.
  
  
  CONCLUSIONS
  The mechanical correlates of abnormal calcium handling or of inactivation failure in the hypertrophied human left ventricle consist of slow and dyssynchronous left-ventricular isovolumic relaxation after left-ventricular unloading and of diastolic left-ventricular aftercontractions, which hinder left-ventricular filling and which are accompanied by delayed afterdepolarizations.
authors.affiliation: Cardiovascular Center, O.L.V. Ziekenhuis, Aalst, Belgium.
authors.forename: W J
authors.initials: WJ
authors.lastname: Paulus
authors.forename: M A
authors.initials: MA
authors.lastname: Goethals
authors.forename: S U
authors.initials: SU
authors.lastname: Sys
mesh_terms: D000200:Action Potentials; D000368:Aged; D001024:Aortic Valve Stenosis / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D005117:Cardiac Complexes, Premature / Q000503:physiopathology; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology*; D003971:Diastole; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D011312:Pressure; D016277:Ventricular Function, Left
chemical_list: D002118:Calcium