INTRODUCTION
Atrial fibrillation (AF) is one of the most common forms of cardiac
arrhythmia that is associated with not only increased mortality but also
the progression of heart failure (HF) and an increased frequency of HF
hospitalisation.1 2 The incidence and prevalence of AF
are expected to double in the next 20 years, with corresponding
increases in the mortality rate and medical cost.3 4Some risk factors such as old age and combined coronary artery disease
(CAD) are known predictors of adverse outcomes in patients with
AF.5 In the setting of sinus rhythm, both systolic and
diastolic dysfunctions are well-known risk factors of adverse outcomes
such as mortality and HF hospitalisation.6 7 However,
data regarding the relationship between diastolic dysfunction and
adverse cardiac events in patients with AF are insufficient. Moreover,
in the setting of chronic AF, prediction of the status of diastolic
function is exceedingly difficult.8 During progression
of diastolic dysfunction, elevated left ventricular end-diastolic
pressure (LVEDP) reflects the extent of diastolic
dysfunction.9 10 However, no studies have evaluated
the relationship between elevated LVEDP and adverse cardiac outcomes in
patients with chronic AF. Therefore, the aim of the present study was to
clarify the prognostic significance of systolic and diastolic
dysfunctions in patients with chronic persistent AF by evaluating the
relationship of systolic dysfunction as well as elevated LVEDP, which
can reflect the extent of diastolic dysfunction, with the 3-year
clinical outcomes.
METHODS
Study design and population
We evaluated data for 114 consecutive patients with chronic AF who
underwent measurement of LVEDP at our hospital between 1 March 2011 and
31 December 2014. All patients presented with symptoms such as
unexplained dyspnea, chest discomfort, and chest pain and underwent
coronary angiography after providing informed consent. We excluded
patients with paroxysmal AF, mitral stenosis, rheumatic disease, severe
mitral regurgitation, moderate to severe aortic stenosis, severe aortic
regurgitation, prosthetic valve disease and severe tricuspid
regurgitation, and/or right ventricular dysfunction. The included
patients were divided into two groups according to their left
ventricular ejection fraction (LVEF): LVEF < 50 (n = 24; REF
group) and LVEF ≥ 50 (n = 90; PEF group). For evaluation of the outcomes
with regard to diastolic dysfunction, the PEF group was further divided
into two subgroups according to the left ventricular end-diastolic
filling pressure (LVEDP): LVEDP >15 mmHg (n = 38) and LVEDP
≤15 mmHg (n = 52). Clinical data were obtained by face-to-face
interviews in the outpatient clinic and/or telephone interviews, a
complete review of electronic medical records, physical examinations,
history taking, laboratory examinations, echocardiography, and
haemodynamic measurements.
This single-centre study was performed at a university hospital, and the
protocol was approved by the institutional review (IRB) board of the
hospital (IRB approval number: 2015-14). All patients or their legal
guardians were provided a thorough written and verbal explanation of the
study procedures, following which they gave written consent for
participation in the study.
Echocardiography and haemodynamic measurements
A single experienced physician performed baseline transthoracic
echocardiography (TTE) with the patient in the left lateral decubitus
position within 24 h before the measurement of LVEDP using a GE Vivid 7
device equipped with M4S transducers (GE Medical, Milwaukee, USA). All
measured images were digitally recorded for subsequent analysis.
Measured echocardiographic parameters included the ejection fraction
(EF), left ventricular end-diastolic diameter (LVEDD), left ventricular
end-systolic diameter (LVESD), left atrial volume, degree of mitral and
aortic regurgitation, and stenosis. LVEF was calculated using the
biplane modified Simpson’s method.11 Echocardiographic
Doppler parameters were also measured and stored. The transmitral flow,
mitral annular motion velocity, E-wave deceleration time (DT), and
propagation velocity (Vp) were recorded for five consecutive cardiac
cycles, and the results were averaged. LVEDP and the minimal LV filling
pressure were measured using a 5-Fr pigtail catheter positioned at the
left ventricle and aorta during coronary angiography. LVEDP was measured
at the Z-point, which is identified on the left ventricular pressure
traceas the point at which the slope of the ventricular pressure
upstroke changes, and averaged over 10 consecutive
beats.12 An investigator blinded to the
echocardiographic data acquired the pressure values.
Clinical outcomes
The 3-year clinical outcomes were evaluated and compared between the REF
and PEF groups andthe two LVEDP groups. Clinical outcomes, including the
mortality rate; incidences of stroke, AF with rapid ventricular rhythm
(RVR), and bleeding; and rate of HF hospitalisation, were recorded for
all patients. RVR was defined as a ventricular response of
>100 beats/min at presentation. Bleeding referred to major
bleeding that was fatal or intracranial or affected another critical
anatomical site, or overt bleeding causing a decrease in haemoglobin of
≥20 g/L or necessitating transfusion of ≥2 units of erythrocytes.
Data analyses
Intergroup differences in continuous variables, presented as means ±
standard deviations, were evaluated by Student’s t-test. Differences in
categorical variables, expressed as numbers and percentages,were
analysed using the χ2test or Fisher’s exact test as
appropriate. Kaplan–Meier curves were generated for determination of
the time-dependent HF hospitalisation rate, with comparisons performed
using the log-rank test. Cox proportional hazards models were used to
estimate the risk factors for HF hospitalisation during the 3-year
period, with calculation of hazard ratios (HRs) and 95% confidence
intervals (95% CIs). A two-sided p-value of <0.05 was
considered statistically significant in all tests. All statistical
analyses were performed using SPSS 20 (IBM SPSS., Chicago, IL, USA).
RESULTS