Results:
Our prospective study basically included 73 patients diagnosed as HFrEF
based on conventional echocardiography study at the outpatient clinic of
Menoufia university hospital, a total of 12 cases were excluded during
the workflow of the follow ups either because of three cases missed
connections, four cases developed severe renal impairment and CKD, three
cases were uninterested to continue follow up, and four cases died of
sudden cardiac death. Sixty-one patients succeeded to complete the time
table of the study, 34 cases were treated by ARNI (ARNI group) and 27
cases were treated by traditional therapy (Traditional group), data
reveled that at baseline there were no significant difference in between
the traditionally treated and ARNI treated groups regarding basic
characteristics, demographic data, symptoms, conventional and STE
echocardiographic measurements. (Table.1)
After 6 months, both groups recalled doing the first follow up and there
were remarkable differences in symptoms, conventional and STE
echocardiography data (Table.2) there were very high statistically
significant improvement in diastolic parameters either conventional E/A,
E/e’, Tricuspid velocity or STE specifically untwist parameters (Untwist
onset, and rate).while the ejection fraction and global LV longitudinal
strain showed also improvement. For the final recall after 11 months,
the data showed exponential improvement for both diastolic and systolic
parameters with very high statistically significant improvement of
untwist and twist parameters with remarkable improvement of ejection in
the ARNI group versus the traditionally treated patients. (Table.3)
On another hand to show the pattern of temporal effect of ARNI therapy
among the ARNI group itself we made comparisons between the ARNI group
at different follow-ups and it also showed exponential improvement from
baseline, 6 months and 11 months follow up with maximal improvement of
untwist parameters, twist and ejection fraction after 11 months of
follow up. (Table.4, 5)
As regard the ejection fraction of the ARNI group after 11 months it was
positively correlated with LVGLS, Twist, Apical rotation, and negatively
correlated with Untwist onset, and rate and basal rotation.
(Table.6)(Figures1, 2, 3 and 4)
From all of these variables the only dependent variables for the
improvement of EF% was the LVGLS, and Apical rotation. (Table.7)
As regard the prevalence of systemic hypertension in ARNI group it was
(22cases from 34 ARNI treated patients (64%), we did comparison between
baseline and 11 months follow up, data showed highly significant
improvements in untwist and twist parameters, LVGLS% and EF% in
comparison to the weaker however significant improvements in the
normotensive group (12 cases).(Table.8,9)
Discussion:
The sound evaluation of cardiac function plays a crucial role in
diagnosing cardiovascular diseases, initiating specific therapeutic
interventions, monitoring treatment, and determining the prognosis of a
variety of cardiovascular conditions. Echocardiography can provide
valuable information about the anatomy and function of the heart. (15,
16) Left ventricular ejection fraction (LVEF) provides objective
information about left ventricular (LV) systolic function. It has been
used to diagnose and classify heart failure (HF),(17,18),determine the
suitability of device therapy,(17,19) decide interventions for valvular
heart diseases (VHDs),(20,21) determine the need for specific
medications,(19) and predict prognosis.(22) However, LVEF is a
volumetric parameter with ventricular load-dependence and had
limitations such as significant inter- and intra-observer variability
and geometric assumptions.(23) Moreover, LVEF does not represent
intrinsic myocardial properties.
Strain is a dimensionless index of a change in length between 2 points
before and after movement. Strain echocardiography was introduced to the
clinical field about 20 years ago, making it a relatively new
echocardiographic modality that can measure myocardial deformation.
Unlike LVEF, myocardial strain, as calculated by strain
echocardiography, can afford indices of regional and global myocardial
systolic function noninvasively and objectively. (24)
Strain echocardiography has been used to diagnose subclinical disease
states, (25, 26) monitor changes in myocardial function with specific
therapies, (27) differentiate cardiomyopathies, (28) and predict the
prognosis of several cardiovascular diseases independently of LVEF. (29,
30)
Although the physiological mechanisms of action of Sacubitril/Valsartan
are well described, its effects on left ventricular remodeling and left
ventricular ejection fraction (LVEF) have not been well studied. Left
ventricular remodeling is a major mechanism underlying disease
progression in patients with HFrEF (31). The degree of improvement in
left ventricular end-diastolic volume (LVEDV), left ventricular
end-systolic volume (LVESV), LV dimensions, and LVEF with therapies are
strongly correlated with clinical outcomes, including survival (32).
In the current study, we demonstrated that after 6 months of follow up
on the ARNI treated group of patients the symptoms of congestion and
dyspnea was remarkably improved this is accompanied with the improvement
of diastolic indices that might be explained by a chronic state of LV
deloading and reduction of LV end diastolic pressure indexed by the
reduction of the tricuspid flow velocity, E/A , E/e’ also that could
help in the initial improvement of LV global longitudinal strain which
indicating that the maximized stretch of LV myocardium and wall tension
are reduced with restoration of myocardial starling’s forces and this
state prepare the LV myocardium recovering the global longitudinal
strain. Beta-blockers, ACEi/ARBs, and MRAs have demonstrated potent
effects on reverse remodeling and improvement in LVEF in multiple
studies (33-36) Animal studies have shown that treatment with
Sacubitril/Valsartan compared to Valsartan alone is associated with a
statistically significant increase in LVEF and a trend towards improved
reverse remodeling (37).
Heart failure has recently been classified according to alterations in
the mechanical function of the LV
(38).
After having observed anomalous specific patterns of ventricular
myocardial mechanics in different subsets of patients with heart
failure, an alternative approach has been proposed for its
characterization
(38, 39).
Accordingly, heart failure can be classified into three large subgroups:
A) Predominant longitudinal dysfunction; B). Transmural dysfunction
(longitudinal and circumferential); and C). Predominant circumferential
dysfunction. This classification is based on the orientation of the
myocardial fibers of the LV, which are arranged obliquely in a double
helix shape. Endocardial fibers, which are aligned in a parallel fashion
to the LV long axis, are mainly associated with longitudinal mechanics,
while transmural fibers are mainly responsible for circumferential
mechanics (40). The action of the latter is predominant due to its
greater radius of action.
In the case of systolic dysfunction, twist serves as a compensatory
mechanism, and the more its reduction the more advanced stage of the
disease. In the dilated left ventricle, the fiber muscles in both layers
are stretched and oriented more circumferentially, which leads to
additional reduction in chamber contractility and torsion (41, 42).
Thus, twist and torsion may be a sensitive marker of remodeling of LV
wall architecture, useful in the monitoring of disease progression and
response to therapy.
The last follow up of our patients groups after eleven months there were
a lot of data that strongly supports the idea of the effect of
Sacubitril/Valsartan of LV ejection fraction, and reverse myocardial
remodeling which might go in agreement with the PROVE-HF trial (43),
where the investigators stated that “although improvement in cardiac
structure and function was present at six months, at 12 months, further
improvement in LVEF and volumes was present, with 25 percent of the
study participants experiencing an absolute LVEF increase of more than
13 percent”. In that trail they depend on changes in LV end systolic,
diastolic and left atrial volumes, but in our study we choose a more
precise STE deformational parameters, which had a more sensitive
predictive values and accuracy, where we demonstrated that at eleven
months most of the torsion mechanics and LV global longitudinal strain
consequently LV ejection fraction in addition to the diastolic
parameters as untwist rate and onset, that means systolic functional
improvement and LV recovery.