Clinical outcomes of the participants according to LVEDP
The 3-year clinical outcomes of patients in the LVEDP >15
mmHg and LVEDP ≤15 mmHg groups are presented in Table 5. There were no
significant differences between the two groups. Although the rate of HF
hospitalisation tended to be higher in the LVEDP >15 mmHg
group, the difference was not statistically significant (15.4% vs
21.1%, p = 0.58). Time-dependent Kaplan–Meier analyses and log-rank
tests showed no difference in the rate of HF hospitalisation between the
two groups (Fig 1b).
DISSCUSSION
In the present study, we evaluated the relationship of systolic
dysfunction as well as the level of LVEDP with the 3-year clinical
outcomes in patients with chronic AF. The main results of our study were
as follows. First, systolic dysfunction was related with adverse
outcomes such as heart failure (HF) hospitalisation and the occurrence
of AF with rapid ventricular rhythm during the 3-year observation
period. In addition, systolic dysfunction (LVEDP < 50%) was
an important independent predictor of HF hospitalisation. Second,
elevated LVEDP, which is the key finding in patients with diastolic
dysfunction, was not associated with mid-term adverse outcomes. To our
knowledge, this is the first study to assess the effect of increased
LVEDP on mid-term outcomes in patients with chronic AF. These results
highlight the importance of paying more attention to a low EF detected
by echocardiography than to diastolic parameters in patients with
chronic AF.
AF is one of the most common forms of cardiac arrhythmia requiring
treatment, and it is associated with increased rates of mortality and
hospitalisation.1 4 Some previous studies of patients
with AF also showed that patients with systolic dysfunction more
frequently exhibit all-cause mortality than do patients with a preserved
EF.13-15. In a previous study, AF was theoretically
associated with the development of rapid rhythm, loss of atrial
contractility, and left atrial enlargement. These changes can lead to
left ventricular wall thickening, neurohormonal changes, and systolic
dysfunction, which is an important predictor of adverse cardiac
outcomes.5 16 However, in the present study, the
mortality rates for patients with REF and those with PEF were
comparable; this was probably because of the relatively short
observation period, small number of patients in the REF group, and event
rates. Although many studies have demonstrated a high mortality rate and
increased HF hospitalisation in patients with AF and reduced LVEF, a few
studies showed that reduced LVEF did not increase the HF hospitalisation
or stroke rate for patients with AF and HF, relative to the rates for
patients with AF and diastolic dysfunction.17 18 In
the present study, the HF hospitalisation rate was significantly higher
in the REF group than in the PEF group, with the rate being as high as
29.2% in the former group. These findings could be carefully explained
by the relatively old age of the enrolled patients and the presence of
chronic persistent AF in all patients (patients with paroxysmal AF were
excluded).
Notably, the prognostic utility of LVEF measurements for patients with
AF is well established. However, in a very recent study, the authors
compared the long-term prognostic implications of AF and sinus rhythm in
patients with acute or chronic HF stratified according to the level of
LVEF and found that AF was not associated with worse cardiovascular
outcomes in patients with reduced LVEF.19 These varied
results could be caused by the complexity of AF. Therefore, prediction
of our results was difficult, and we carefully estimated that elevated
LVEDP would be related with adverse clinical outcomes. Studies that
investigated the relationship between LVEDP and clinical outcomes are
very limited because of the invasiveness of measurement methods.
Previously, some investigators reported that elevated LVEDP is an
important risk factor for adverse clinical outcomes in patients with
acute myocardial infarction.20-22 To our knowledge,
however, no study has evaluated the association between LVEDP and
clinical outcomes in patients with chronic AF. Only left ventricular
diastolic dysfunction (LVDD), measured by non-invasive tests such as
echocardiography, was proven to be correlated with adverse clinical
events such as hospitalisation and stroke.23-25However, in the setting of AF, atrial contractile a synchronicity
complicates the assessment of LVDD using classic echocardiographic
parameters.26 27 The physiological hallmarks of LVDD
are impaired relaxation and reduced diastolic compliance, which increase
the LV filling pressure. 28 29 Among patients with
normal systolic function, elevated LVEDP could represent early diastolic
dysfunction or could be the main physiological consequence of diastolic
dysfunction.30 We not only determined the relationship
between LVEDP and clinical outcomes in patients with chronic AF and a
preserved EF but also clarified the relationship between diastolic
dysfunction and adverse clinical outcomes such as mortality, stroke, and
HF hospitalisation. We found that echocardiographic parameters that
represent diastolic function, such as E/e’ and E/Vp, were worse in the
LVEDP> 15 mmHg group. However, during the 3-year
observation period, no significant differences were found in terms of
adverse clinical outcomes between the LVEDP > 15 mmHg and
LVEDP ≤ 15 mmHg groups. We speculate that chronic persistent AF leads to
irreversible, chronic structural and neurohormonal changes that could
affect both LVEDP and the clinical outcomes.
This study has some limitations, the main one being the retrospective
design without randomization. The number of patients was small and the
follow-up period relatively short. Because it was a single-center study,
it was difficult to collect an adequate number of patients with LV
pressure wave data and recruit a relatively homogenous group with
chronic persistent AF without valvular heart disease. Long-term clinical
follow-up will be necessary after recruitment of more patients,
particularly those with reduced LVEF. Even if we performed coronary
angiography on the basis of its broad indications, LVEDP measurements
were recorded for selective patients with symptoms such as unexplained
chest discomfort, unexplained broad-spectrum dyspnoea, and typical and
atypical chest pain. Further studies with long-term follow-up periods
are necessary after the recruitment of more patients for clarification
of the relationship between diastolic dysfunction or elevated LVEDP and
clinical outcomes. Furthermore, the number of patients treated with oral
anticoagulants was very low in our study, primarily because our hospital
is located in a rural area and the insurance system in Korea did not
cover treatment with direct oral anticoagulants during the study period.
Thus, the level of education and medical compliance were low, and the
patients frequently refused warfarin treatment because of the
inconvenience of blood sampling. Finally, LVEDP is affected by multiple
factors such as dehydration and volume overload (e.g. combination of
chronic kidney disease and anaemia), and elevated LVEDP cannot represent
diastolic dysfunction, particularly in the setting of chronic AF.
CONCLUSION
Despite the study limitations, the findings are clinically meaningful
because we investigated, for the first time, the relationship between
elevated LVEDP and mid-term clinical outcomes along with the
relationship between systolic dysfunction and clinical outcomes in
patients with chronic AF. Also, this study proved that diastolic
dysfunction itself does not appear to be a prognostic factor for
hospitalization due to heart failure. Clinicians should apply these
results during the treatment of patients with chronic AF, with careful
evaluation of systolic function and prevention of risk factors that lead
to LV systolic dysfunction.
CONTRIBUTORS
JH AHN conceptualized the study. JH AHN and HY YU cleansed the data. JH
AHN and HY YU analyzed the data. JH AHN and HY YU reviewed the data
analysis. JH AHN and HY YU wrote initial draft. JH AHN and HY YU
reviewed the manuscript and interpreted the findings.
COMPETING INTERESTS
None declared