Load-independent index of diastolic filling: model-based derivation with in vivo validation in control and diastolic dysfunction subjects.
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)) proportional, variant 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.
Shmuylovich
Leonid
L
Cardiovascular Biophysics Laboratory, Washington University School of Medicine, St. Louis, Missouri, USA.
Kovács
Sándor J
SJ
D000328:Adult; D001794:Blood Pressure / Q000502:physiology*; D002404:Catheterization / Q000379:methods; D003971:Diastole / Q000502:physiology; D015150:Echocardiography, Doppler / Q000379:methods; D005260:Female; D006334:Heart Function Tests / Q000379:methods* / Q000592:standards; D006801:Humans; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D008962:Models, Theoretical; D015203:Reproducibility of Results; D013318:Stroke Volume / Q000502:physiology*; D013599:Systole / Q000502:physiology; D018667:Tilt-Table Test; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D016276:Ventricular Function