Passive Stiffness of Myocardium From Congenital Heart Disease and Implications for Diastole

Rajiv R. Chaturvedi, Todd Herron, Robert Simmons, Darryl Shore, Pankaj Kumar, Babulal Sethia, Felix Chua, Efstathios Vassiliadis, Jonathan C. Kentish

Research output: Contribution to journalArticlepeer-review

132 Citations (Scopus)

Abstract

Background-In ventricular dilatation or hypertrophy, an elevated end-diastolic pressure is often assumed to be secondary to increased myocardial stiffness, but stiffness is rarely measured in vivo because of difficulty. We measured in vitro passive stiffness of volume-or pressure-overloaded myocardium mainly from congenital heart disease. Methods and Results-Endocardial ventricular biopsies were obtained at open heart surgery (n = 61; pressure overload, 36; volume-overload, 19; dilated cardiomyopathy, 4; normal donors, 2). In vitro passive force-extension curves and the stiffness modulus were measured in skinned tissue: muscle strips, strips with myofilaments extracted (mainly extracellular matrix), and myocytes. Collagen content (n = 38) and titin isoforms (n = 16) were determined. End-diastolic pressure was measured at cardiac catheterization (n = 14). Pressure-overloaded tissue (strips, extracellular matrix, myocytes) had a 2.6- to 7.0-fold greater force and stiffness modulus than volume-overloaded tissue. Myocyte force and stiffness modulus at short stretches (0.05 resting length, L-0) was pressure-overloaded > normal approximate to volume-overloaded > dilated cardiomyopathy. Titin N2B: N2BA isoform ratio varied little between conditions. The extracellular matrix contributed more to force at 0.05 L-0 in pressure-overloaded (35.1%) and volume-overloaded (17.4%) strips than normal myocardium. Stiffness modulus increased with collagen content in pressure-overloaded but not volume-overloaded strips. In vitro stiffness modulus at 0.05 L-0 was a good predictor of in vivo end-diastolic pressure for pressure-overloaded but not volume-overloaded ventricles and estimated normal end-diastolic pressure as 5 to 7 mm Hg. Conclusions-An elevated end-diastolic pressure in pressure-overloaded, but not volume-overloaded, ventricles was related to increased myocardial stiffness. The greater stiffness of pressure-overloaded compared with volume-overloaded myocardium was due to the higher stiffness of both the extracellular matrix and myocytes. The transition from normal to very-low stiffness myocytes may mark irreversible dilatation. (Circulation. 2010; 121: 979-988.)
Original languageEnglish
Pages (from-to)979 - 988
Number of pages10
JournalCirculation (Baltimore)
Volume121
Issue number8
DOIs
Publication statusPublished - Mar 2010

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