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.