Heart failure and limit to cardiomyocyte hypertrophy: Lessons from autopsies

Abstract

Objective: An overworked ventricle faces a limit to hypertrophy; it cannot be forced to a size appropriate for a horse, and this effect needs an explanation. Methods: The data file analyzed here was generated by merging two series of cases, (1) dynamic left ventricle (LV) dimensions abstracted from published echocardiographic reports (Clin) and (2) myocyte transverse size measured in postmortem hearts (Path) (excluding ischemic, valvular, and assorted uncommon conditions). Results: With increasing volume overload from growth and obesity stroke work and LV chamber diameter increased up to impossible limits where three effects were noted: (1) Progressively declining systolic sarcomere excursion approached the limit of zero contraction when systolic sarcomere length drew equal to diastolic length. (2) Midwall stress rose to exceed the known capability for isolated myofibrils to generate maximal isometric stress. (3) Endocardial fractional shortening declined to reach an impossible minimum. Conclusions: When systolic heart failure is provoked by volume overload it should be feasible to test these hypotheses: (1) The limits to hypertrophy may be imposed by left ventricle geometry constrained by a fixed number of myocytes. (2) After reaching these limits, only then might contractile weakening supervene.