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1 Cardiovascular Division, Deparment of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, United States; Department of Physics, Washington University, Saint Louis, Missouri, United States
* To whom correspondence should be addressed. E-mail: sjk{at}wuphys.wustl.edu.
Maximum elastance (Emax) 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 non-invasive 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 (kxoocpeak atrio-ventricular gradient) to maximum viscoelastic resistive force (cEpeak) 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 maximum driving force (kxo) vs. peak resistive force (cEpeak) yielded kxo=M(cEpeak)+B r2=0.98; M=1.27±0.09, B=5.69±1.70. Effects of diastolic dysfunction (DD) on M were assessed by analysis of preexisting simultaneous cath-echo data in 6 DD vs. 5 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 (LVEDP). Larger M values imply better DF in that increasing A-V pressure gradient results in relatively smaller increases in peak resistive losses (cEpeak). Conversely, lower M implies that increasing A-V gradient leads to larger increases in resistive losses. Further prospective validation characterizing M in well-defined pathological states is warranted.
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