Background
Rhythmic contraction and relaxation of the heart are the bases for
ensuring hemodynamic stability. Various cardiac structural or functional
diseases lead to impaired ventricular filling and/or ejection function,
which, in turn, leads to heart failure (HF). In recent years, the high
prevalence of HFpEF has highlighted the importance of diastolic
dysfunction in the development of HF(1-4). Most patients with HFpEF show
diastolic dysfunction, such as an abnormal left ventricular (LV) filling
pattern and elevated filling pressure(5, 6). Therefore, the evaluation
of cardiac diastolic function and its determinants has important
clinical significance (7-9).
The diastolic process can be divided
into four phases: isovolumic diastole, early diastolic filling,
diastasis, and atrial
contraction. Isovolumic diastole is the period of time between the
closure of the aortic valve and the opening of the mitral valve, when LV
pressure falls while volume remains constant, and usually reflects LV
compliance. When LV pressure is lower than left atrial (LA) pressure,
the mitral valve opens under negative pressure and enters a period of
rapid filling, which is influenced primarily by preload and LV
relaxation properties. As blood enters the left ventricle, the LV
pressure begins to rise, and when it is equal to the LA pressure, the
flow enters a state of relative stagnation, the diastasis phase, which
can be influenced by preload, LV geometry, stiffness of the LV chamber,
and compliance. Atrial systole is the final phase of diastole, when LA
pressure is again higher than LV pressure, and factors affecting this
phase include LV compliance and LA systolic
function(10). Among the factors
affecting diastolic function of the heart, apart from extrinsic factors
such as pulmonary-cardiac contact pressure, pericardial restraint and
interaction of both ventricles (11), intrinsic factors are mainly LV
active relaxation and passive LV chamber stiffness (12). Delayed active
relaxation will result in changes in early filling pressures and
impaired filling function. In turn, changes in LV chamber stiffness can
affect the hemodynamics of early filling, diastole and the atrial
systolic phase. When the mitral valve opens during diastole, the
pulmonary veins, LA and LV form a common chamber and abnormal diastolic
function leads to an increase in left ventricular filling pressure
(LVFP) , resulting in pulmonary oedema and heart failure symptoms, which
may ultimately lead to the development of
HFpEF.
The animal study from Yasushi Sakata
et al(13) demonstrated that the transition from compensatory LV
hypertrophic stage to HFpEF in the hypertensive heart was associated
with the increase in the myocardial stiffness constant, but not with the
changes in the time constant of LV relaxation. The clinical study also
showed that the time constant of LV relaxation was not different between
the HFpEF patients and the control subjects, and that the LV stiffness
was higher in the HFpEF patients than in the control subjects. These
studies proved the important role of LV stiffness in the development of
HFpEF. Most importantly, substantial evidences suggested that LV
stiffness was associated with worse prognosis in patients with HFpEF.
Therefore, early detection of LV stiffness alteration and initiation of
early intervetnions may improve the overall prognosis of patients with
HFpEF.
The
concept of LV stiffness is ambiguous in various studies. Left
ventricular stiffness is not the same as myocardial stiffness, and the
left ventricular stiffness assessed in many studies is in fact left
ventricular chamber stiffness. LV chamber stiffness is an indicator of
the relationship between diastolic volume and pressure, and in the
operating room, a pressure volume catheter can be used to continuously
measure the volume and pressure of the LV to derive the chamber
stiffness (dP/dV). Myocardial stiffness, on the other hand, is the
degree to which the myocardium undergoes strain as a result of stress,
and is a passive physical property of the myocardium itself. Indicators
that can influence LV chamber stiffness may include LV geometry,
myocardial stiffness and other extra LV factors such as pericardial,
right ventricular and interventricular synchrony, etc.
At the molecular level, indicators
of myocardial stiffness include myosin, microtubule and extracellular
matrix composition, etc(14).
However, the application of this parameter is limited since its
measurements requires a highly invasive and specialized technique of
catheterization. Therefore, an easily applied, noninvasive technique is
urgently needed. As a non-invasive, simple and easy-to-use tool for
cardiac function evaluation, cardiac ultrasound is increasingly being
used in clinical practice, and the combination of multiple indices is
particularly important for a comprehensive assessment of cardiac
function. Previously, indicators associated with pulsed-wave tracings of
mitral inflow including E velocity of mitral inflow, the deceleration
time, the velocity of the mitral A wave as well as the ratio of E/A, are
frequently used to assess LV filling. However, these indices do not
enable indirect measurement of LV stiffness. With advances in ultrasound
technology, new advances have been achieved in the assessment of LV
chamber or myocardial stiffness using noninvasive echocardiography.
Therefore, this review was carried
out to summarize the pathophysiological mechanisms, correlations with
invasive LV stiffness constant (Table 1), applications in different
populations as well as the limitations of echocardiography-derived
indices for assessment of both LV chamber and myocardial stiffness,
aiming to improve our abilities in evaluating LV stiffness
non-invasively.