Page 12 - CBAC Newsletter 2015

key insight in solving the LIIDF problem lies in analyzing functional elegance of macroscopic ‘diastolic function’
not just one, but several E-waves, acquired at varying can only be fully appreciated using a conceptual
loads (see figure 3). The key insight in solving the framework that includes a causal, mechanistic
LIIDF problem lies in analyzing not just one, but several description of events. Accordingly, the focus has been
E-waves, acquired at varying loads (see figure 3). To on the basic rules that govern diastole. These are:
determine the LIIDF, first determine the PDF parameters four-chambered (nearly perfect) constant-volume pump,
stiffness (k, c, x ) for each E-wave and measure Epeak. 2) all LVs (and RVs) initiate filling by being mechanical
o
For each E-wave, the product kx gives the model suction pumps, 3) diastatic LV volume defines in-vivo
o
predicted maximum driving force, i.e. the analog of the equilibrium volume, and 4) all four heart chambers are
peak instantaneous atrio-ventricular pressure gradient. volume-pumps for the entire cardiac cycle, except for
The product of each E-wave’s c and E peak defines the the LV, which is a pressure-volume pump in systole. The
maximum resistive force opposing flow. Thus, for each consequences of these rules governing diastole become
E-wave we compute kx and the associated cE peak , and explicit when expressed in mathematical form, which is
o
plot a point in the kx vs. cE peak graph. The LIIDF is the predictive and subject to experimental verification, and
o
slope, called M, of the linear regression between all has lead to new understanding in physiology. According-
(cE peak , kx ) points, where each point is extracted from a ly, the PDF formalism has facilitated a causal,
o
separate E-wave acquired under variable. mechanistic explanation of previously unrelated
observations under a single paradigm: all E-wave
Initially recorded E-waves were in healthy volunteers contours are predictable because they obey the same
subjected to tilt-table maneuvers to change load, and equation of motion (9), isovolumic relaxation (tau vs.
cardiac catheterization patients undergoing simul- logistic time constant) is governed by an equation of
taneous (micromanometric transducer) LV pressure motion that provides a load independent index of IVR
recording and transthoracic echocardiography for (3,33), in-vivo equilibrium volume occurs at diastasis
E-wave recording in response to load variation due to (35) and it determines passive diastatic chamber
respiration. Healthy subjects showed significant E-wave stiffness (37), a load independent index of diastolic
shape changes as tilt angle was varied from upright function [LIIDF] can be computed from E-wave analysis
to supine to head-down. Despite the dramatic visual (23), E-wave deceleration time is determined by both
E-wave shape variation, all associated (cE peak , kx ) points chamber stiffness and relaxation, rather than stiffness
o
remained co-linear (R2=0.98), demonstrating that the alone (36) and fractionation of E-wave deceleration
slope of the kx vs. cE peak regression is independent of time into stiffness and relaxation components (27,28)
o
load. Furthermore, we found that in subjects undergoing facilitates diastolic function characterization. Continued
cardiac catheterization the LIIDF M was significantly utilization of the framework and methodology discussed
lower in subjects having diastolic dysfunction (elevated is certain to further elucidate and characterize the sur-
filling pressures > 18 mmHg), compared to subjects prising, counterintuitive and elegant features of diastole.
with normal diastolic function (Figure 4). Thus, the LIIDF
can be easily determined by analysis of load-varying
E-waves, it remains constant after load variation, and
differentiates between normal diastolic function and
diastolic dysfunction. The method of LIIDF determina-
tion relies critically on the differences between E-wave
shapes. The practical utility and clinical power of the
LIIDF resides in its application in sequential studies
where each subject serves as their own control. By this
approach, whether therapy has resulted in 'beneficial’ or
‘adverse' remodeling can be assessed in load-
independent terms. Furthermore the LIIDF in and of
itself can serve as a therapeutic target.

Conclusions

Although I have not discussed the complex and coun-
terintuitive cellular features of myocyte contraction and
relaxation, cell geometry and topology and electrical
attributes as they relate to diastole, the meaning and

6 | CBAC Center Heartbeat