Ratios of echocardiographic surrogates of LVFP to LV size
The
left ventricle, left atrium and pulmonary veins are a common conduit and
abnormal diastolic function can all lead to an increase in LV
end-diastolic pressure (LVEDP), mean left atrial pressure (MLAP) and
pulmonary capillary wedge pressure (PCWP). All these pressures are
commonly referred to as LVFP(15). However, there are important
pathophysiological differences between these pressures, and different
pressure profiles can be drawn by invasive catheter manometry. Invasive
monitoring shows three discontinuous pressure changes in LV diastole
(Figure 1): the lowest or minimum pressure in early diastole, the second
before the ventricular A wave, and the third at the end of diastole. LAP
also changes during diastole. LVFP decreases during isovolumic diastole
until it falls below LAP, prompting mitral valve opening and subsequent
blood flow from the atria to the ventricle. When the two chambers reach
pressure equilibrium, blood flow is minimal and LAP matches LVFP until
the atria contract, producing a further pressure difference, and blood
flows through the mitral valve again until pressure equilibrium is
reached and the valve closes. LAP is equal to LVFP until atrial
contraction and the generation of an A wave, but is lower than LVEDP
after atrial contraction is complete.
The assessment of LVFP is an
important component for the evaluation of LV diastolic function and
chamber stiffness. Although the use of the Swan-Ganz catheter is the
gold standard, several studies in
recent years have found that non-invasive cardiac ultrasound
measurements of filling pressures do not differ significantly from the
gold standard (16, 17). Substantial evidences have proved that the ratio
of early diastolic transmitral flow velocity to early diastolic
myocardial velocity using tissue Doppler tracing (E/e’) correlates well
with LVFP (18-24). Meta-analysis study by Rachel Jones et al.
demonstrated a moderate correlation between E/e’ and invasive LVEDP
(r=0.55, 95% CI 0.46-0.62, P=0.01) (25).In addition, with the addition
of indices from speckle tracking technology (STE), a number of new
integration metrics have been created. The pooled meta-analysis by
Lassen MCH et al. showed a significant correlation between E/early
diastolic strain rate (SRe) and LVEDP measured invasively (Cohen’s
d=5.30 95% CI [2.83–9.96], p<0.001)(26).
According to the definition of LV chamber stiffness, researchers
hypothesized that LV chamber stiffness may be indirectly evaluated by
applying the ratios of echocardiographyic surrogates of LVFP to LV size
(Figure 2A). In line with the hypothesis, Chowdhury SM et al.(27) found
in a population of pediatric heart transplant recipients (n=18) that
lateral E/e’/LVEDV (r=0.59, P<0.01), septal E/e’/LVEDV(r
=0.57, P<0 .01), and (E/circumferential SRe)/LVEDV (r=0.54,
P<0.01) significantly correlated with the chamber stiffness
constant β, and lateral E/e’/LVEDV displayed a C statistic of 0.93 in
detecting patients with abnormal LV stiffness(β>
0.015mL-1). Furthermore, A lateral E/e’/LVEDV of
>0.15 mL-1 had 89% sensitivity and 93%
specificity in detecting an abnormal β. Thereafter, the DPVQ, whose
principle is similar to E/e’/LVEDV, is also a non-invasive parameter
obtained by three-dimensional echocardiography (3DE) and Doppler tissue
imaging (DTI). The LV volume was measured by 3DE and E/e’ was measured
by DTI, after which DPVQ was obtained. Kasner et al.(28) applied this
index to the HFpEF population and compared it with LV chamber stiffness
calculated by invasive cardiac catheterization. Significant differences
for DPVQ were found between 23 HFpEF patients and normal controls
[0.14(0.12–0.17) vs. 0.07(0.06–0.0.09), P<0.001) and there
was a significant correlation between DPVQ and LV chamber stiffness (r =
0.91, P < 0.001).
Although the ratios of
echocardiographic surrogates of LVFP to LV size are currently used to
evaluate LV chamber stiffness, it still remains an issue of concern that
all above mentioned methods(E/e’/LVEDV, E/SRe/LVEDV and DPVQ) are
surrogate and lumped measurements, relying on E/e’ or E/SRe for
evaluating LVFP. However, there are several limitations and
controversies for the validities of E/e’ in the assessment of LVFP.
Firstly, in terms of measurement, both E and e’ are strictly limited by
the location of the sample and e’ is also dependent on the angle of
measurement (<20°). Secondly, the ratio is susceptible to a
number of factors such as hemodynamics, myocardial synchronization, and
ventricular wall segmental motion(29). Park JH et al. also suggested in
their review that the use of E/e’ may be unreliable in situations such
as tachycardia with fusion of E and A velocities, significant mitral
regurgitation (>2+), mitral valve repair or replacement,
severe mitral annular calcification, significant mitral stenosis and
presence of left bundle branch block(30). Most importantly, in terms of
diagnostic accuracy, a systematic review and meta-analytic analysis from
Sharifov OF et al. pointed out that there was insufficient evidence to
support that E/e’ could reliably estimate LVFP in patients with
preserved LVEF(31). The summary sensitivities and specificities for
lateral E/e’, mean E/e’, and septal E/e’ in detecting elevated LVFP were
30% and 92%, 37% and 91%, and 24% and 98%, respectively.
Additionally, we reviewed 37 literatures on the correlation between E/e’
and each LVFP (LVEDP, M-LVDP, Pre-A LVP, LAP and PCWP) (supplemental
material 1). In agreement with previous studies, it was found that in
patients with HFrEF and HFpER, the correlation between E/e’ and each
pressure varied considerably: LVEDP (0.03-0.84 vs 0.11-0.80), M-LVDP
(0.40-0.52 vs. 0.49-0.60), Pre-A LVP (0.02-0.63 vs. 0.19-0.76), LAP
(0.46-0.52) and PCWP (0.19-0.91 vs. 0.083-0.78)(25, 31, 32). All these
disadvantages may limit these indices in clinical use. Other parameters
which could reliably and accurately assess LVFP warrant further
uncovered.
Encouragingly, the ratio of early filling rate derived from the time
derivative of LV volume to SRe (FRe/SRe) (33) has the potential to be a
surrogate marker of LVFP. It was reported that in nondilated hearts,
FRe/circumferential-SRe and FRe/ area-SRe may be more useful to
accurately assess LVFP than E/e’. In addition, LA longitudinal strain
derived from STE is also sensitive in estimating intracavitary
pressures. It is angle-independent, thus overcomes Doppler limitations
and provides highly reproducible measures. Cameli M et al. found that
the E/e’ correlated poorly with invasive LVFP in a group of patients
with advanced systolic heart failure (r=0.15). However, the LA
longitudinal deformation (PALS) correlated well with PCWP (r=-0.81,
p<0.0001), and a cut-off value of less than 15.1% had a high
sensitivity and specificity of 100% and 93% in predicting elevated
LVFP(34). Similarly, Cameli M et al. noted in their study that both the
PALS and mean E/e’ correlated well with LVEDP in patients with preserved
(r=-0.79 vs. r=0.72) or mildly reduced LVEF (r=-0.75 vs. r =0.73).
However, compared to mean E/e’, PALS displayed a better performance in
assessment of LVEDP in patients with moderately (r=-0.78 vs. r=0.47) or
severely (r =-0.74 vs. r=0.19) reduced LVEF(35).
More invasive studies are yet to
be performed to further explore and confirm the relationship between the
ratio of FRe/SRe or PALS to LV size and LV chamber stiffness.