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Load-independent index of diastolic filling: model-based derivation with in vivo validation in control and diastolic dysfunction subjects

Cardiovascular Biophysics Laboratory, Washington University School of Medicine, St. Louis, Missouri

Submitted 12 October 2005 ; accepted in final form 20 March 2006

Maximum elastance is an experimentally validated, load-independent systolic function index stemming from the time-varying elastance paradigm that decoupled extrinsic load from (intrinsic) contractility. Although Doppler echocardiography is the preferred method of diastolic function (DF) assessment, all echo-derived indexes are load dependent, and no invasive or noninvasive load-independent index of filling (LIIF) exists. In this study, we derived and experimentally validated a LIIF. We used a kinematic filling paradigm (the parameterized diastolic filling formalism) to predict and derive the (dimensionless) dynamic diastolic efficiency M, defined by the slope of the peak driving force [maximum driving force (kx_o) peak atrioventricular (AV) gradient] to maximum viscoelastic resistive force [peak resistive force (cE_peak)] relation. To validate load independence, we analyzed E-waves recorded while load was varied via tilt table (head up, horizontal, and head down) in 16 healthy volunteers. For the group, linear regression of E-wave derived kx_o vs. cE_peak yielded kx_o = M (cE_peak) + B, r² = 0.98; where M = 1.27 ± 0.09 and B = 5.69 ± 1.70. Effects of diastolic dysfunction (DD) on M were assessed by analysis of preexisting simultaneous cath-echo data in six DD vs. five control subjects. Average M for the DD group (M = 0.98 ± 0.07) was significantly lower than controls (M = 1.17 ± 0.05, P < 0.001). We conclude that M is a LIIF because it uncouples intrinsic DF (i.e., the pressure-flow relation) from extrinsic load (left ventricular end-diastolic pressure). Larger M values imply better DF in that increasing AV pressure gradient results in relatively smaller increases in peak resistive losses (cE_peak). Conversely, lower M implies that increasing AV gradient leads to larger increases in resistive losses. Further prospective validation characterizing M in well-defined pathological states is warranted.

diastolic function; Doppler echocardiography; mathematical modeling

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