Discussion
In our study, along with the increasing LVDD grades, the PVR were
increasing and all of the LA functions and the RV systolic functions
showed a decreasing trend. There was a strong correlation between the LA
strain parameters and the PVR.
The RV systolic dysfunction was apparent in grade 3 LVDD in which the LA
contraction function was found to be depressed compared to grade 2
diastolic dysfunction.
In the early stages of LVDD in HFpEF patients, the LA can adapt to
increasing LV filling pressures. When the LA compliance is adequate,
increased LV pressures has no effect on pulmonary circulation. However,
as the LA compliance decreases because of remodeling and fibrosis, the
LA reservoir and the conduit function declines. After this stage, the
pulmonary venous system is exposed to increased LV filling pressure.
These may summarize the progression of grade 1 to grade 2 LVDD in HFpEF
patients (7).
As the pulmonary vascular bed is exposed to increased LV filling
pressure, remodeling in the pulmonary vascular system also takes place,
which in turn results in increased pulmonary vascular resistance and
pulmonary arterial hypertension (16).
Grade 3 LVDD patients have a lower atrial contraction function compared
to both Grade 1 and Grade 2 LVDD patients. PVR estimates showed an
increasing trend with higher LVDD grades. Especially in the Grade 3 LVDD
patient group, the RV-FAC % was found to be lower than the other
groups.
Atrial contraction failure and increased pulmonary vascular resistance
are characteristics of Grade 3 diastolic dysfunction. In further LVDD
grades, LA pump failure and the increase in PVR are concurrent. The
following vicious cycle could cause an increase in the LVDD grade: LA
pump failure results in a further increase of pulmonary venous pressure,
and the further increase of pulmonary venous pressure leads to LA pump
failure.
Simultaneous LA remodeling and pulmonary vascular remodeling could be a
more appropriate explanation for these results. The fibrosis and
hyalinosis especially in the intima of pulmonary veins and simultaneous
fibrosis in LA myocardium may share a common pathophysiology.
Inflammation from mechanical stress on the pulmonary veins and the LA
may result in activation of various neurohumoral-mediated events that
cause fibrosis of both the pulmonary veins and the LA. The severity and
the duration of heart failure syndrome may determine the extent of both
pulmonary venous and LA remodeling (17,18).
The correlation of the peak LA strain with the estimated pulmonary
artery pressures especially in heart failure patients compared with
mid-range EF patients was shown in a previous study. In that study, the
LA strain parameters were worse in patients with mid-range EF, although
the groups have similar LA volumes and LVDD. Possible further LA
remodeling and fibrosis resulting from LV dysfunction could explain
these results in that study (9).
A similar study in HFrEF patients assessed the prognostic significance
of LA reservoir function that was determined using 2DSTE, but the data
were not analyzed according to the LVDD grade. However, in that study
the characteristic features of Grade 3 LVDD, the restrictive mitral
inflow pattern, and the increased pulmonary pressures were predominant
in the lowest peak atrial longitudinal strain tertile. Patients with
acute decompensation were not included in that study and all of the
patients were under optimal medical treatment at least for 3 months.
Chronic exposure of the LA to pressure/volume overload could explain the
results of that study (10).
Another study in HFrEF patients demonstrated the recovery of both of the
reservoir and pump function after appropriate treatment of pulmonary
congestion. These study results could explain the heart failure syndrome
severity impact on LA functions, especially in the acute volume/pressure
overload setting (19).
The parameters to determine RV systolic function were shown to be
correlated with the LA strain parameters in our study. The trend for the
difference in TAPSE and Tr-Sm among groups were also significant, but
the difference for the RV-FAC% was more prominent in Grade 3 diastolic
dysfunction patients. Unlike RV-FAC, TAPSE and Tr-Sm are dependent on
longitudinal RV myocardial function and it may not be informative for
the radial RV function and RV ejection function (20).
The estimated PVR correlates well with the LA strain parameters in our
study. The estimated PVR value that was used in diastolic dysfunction
grading was not evaluated in previous studies for either HFpEF or HFrEF
patients. However, it is well known that the severity of the HF syndrome
and the duration of exposure to increased LV filling pressure determines
both the LA and PV remodeling. In previous studies on the LVDD grading
in HFpEF patients who were evaluated using the 2DSTE-derived LA
functions, LA function deterioration especially for the conduit and
reservoir functions were demonstrated. The calculated LA reservoir
strain parameters were greater in HFpEF patients compared with our
results. This difference suggests the presence of a greater extent of LA
remodeling and fibrosis in HFrEF patients (7). A less severe and shorter
the duration of heart failure syndrome in HFpEF patients could explain
these results.
A longer duration of exposure to increased LV filling pressure and a
more severe heart failure syndrome in HFrEF patients resulted in LA
tissue fibrosis, which suggests that irreversible LA remodeling
occurred. Reduction of atrial pump function in these patients because of
extensive LA remodeling, especially in the Grade 3 LVDD, could explain
our findings.
The estimated PVR correlates well with the LA functions in HFrEF
patients. The possible increased extent LA remodeling and pulmonary
vascular remodeling resulting from a longer duration of exposure to
increased LV filling pressure in HfrEF patients may explain this
finding.