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Harran Üniversitesi Tıp Fakültesi Dergisi (Journal of Harran University Medical Faculty) 2021;18(2):329-335.
DOI: 10.35440/hutfd.948089
329
Research Article / Araştırma Makalesi
Left Atrial Dimension to Left Ventricle Ejection Fraction Ratio Can Predict Long-
Term Major Adverse Events In Patients With Acute Coronary Syndrome
Akut Koroner Sendrom Hastalarında Sol Atriyal Çapın Sol Ventrikül Ejeksiyon
Fraksiyonuna Oranı Uzun Dönem Major İstenmeyen Olayları Öngörebilir
Ömer Faruk ÇIRAKOĞLU 1 , Ahmet Seyda YILMAZ 2 , Göksel ÇINIER 3 , Mustafa ÇETİN 2
1 Ahi Evren Training and Research Hospital, University of Health Science, Department of Cardiology, Trabzon, Turkey
2 Recep Tayyip Erdogan University, Faculty of Medicine, Department of Cardiology, Rize, Turkey
3 Siyami Ersek Training and Research Hospital, University of Health Science, Department of Cardiology, İstanbul, Turkey
Abstract
Background: It is critical to specify the high-risk group in acute coronary syndrome following percutaneous
coronary intervention. Left atrial diameter and Left ventricle ejection fraction are functional echocardiographic
parameters for risk classification thanks to easy obtainable, cheap, and non-invasive nature. However, major
adverse cardiovascular events may be predicted less than actual where ejection fraction or left atrial diameter are
in the normal range. We aimed to assess the left atrial diameter to ejection fraction ratio for major adverse
cardiovascular events prediction in acute coronary syndrome.
Materials and Methods: Individuals with acute coronary syndrome were included in the study. Atrial diameter
and ejection fraction parameters were obtained at admission. The left atrial diameter to left ventricular ejection
fraction ratio was calculated through atrial diameter dividing by ejection fraction, and the relationship between
new-onset heart failure and all-cause mortality with this ratio was investigated for two years period.
Results: The mean age of total 262 patients were 62.1±11.5 years. Thirty-nine (18.9 %) of patients were female
and major adverse cardiovascular events occurred in 73 (28%) of the patients. In the backward multivariable Cox
regression analysis, age [Hazard ratio (HR)=1.039, 95%CI:1.017-1.060, p<0.001], Killip class [HR=2.099,
95%CI:1.011-4.365, p=0.045], serum creatinine level [HR=2.202, 95%CI:1.247-3.811, p=0.003], and left atrial
diameter to left ventricular ejection fraction ratio [HR=1.029, 95%CI:1.019-1.038, p<0.001] were revealed to be
independent predictors of major adverse events.
Conclusion: Left atrial diameter to left ventricular ejection fraction ratio were predictors of two years new-onset
heart failure and mortality in acute coronary syndrome. This novel practical index may provide better prediction
for adverse events in all patient groups.
Key Words: Acute coronary syndrome (ACS), Left atrial diameter (LAd), Left ventricle ejection fraction (LVEF), Left
atrial diameter (LAd) to Left ventricle ejection fraction (LVEF) ratio (LAd/LVEF)
Öz.
Amaç: Akut koroner sendromlu hastalarda perkütan koroner girişim sonrası yüksek riskli grupların belirlenmesi
oldukça önemlidir. Sol ventrikül ejeksiyon fraksiyonu ve sol atrium çapı, kolay elde edilebilebilir, ucuz ve invaziv
olmaması nedeniyle risk sınıflandırması için fonksiyonel ekokardiyografik parametrelerdir. Bununla birlikte, majör
istenmeyen kardiyovasküler olaylar, ejeksiyon fraksiyonu veya atrium çapının normal aralıkta olduğu durumlarda
gerçek olandan daha az tahmin edilebilir. Bu nedenle akut koroner sendrom hastalarında majör istenmeyen olay
öngörüsü için sol atrium çapının sol ventrikül ejeksiyon fraksiyonuna oranının değerlendirilmesini amaçladık.
Materyal ve Metod: Çalışmaya akut koroner sendrom tanısı almış hastalar dahil edildi. Tüm hastalardan sol
ventrikül ejeksiyon fraksiyonu ve sol atrium çapları parametreleri başvuru sırasında elde edildi. Sol atrial çapın sol
ventrikül ejeksiyon fraksiyonuna oranı, sol atriyal çapın ejeksiyon fraksiyonuna bölünmesi ile hesaplandı ve 2 yıllık
takiplerde tüm nedenlere bağlı ölüm ve yeni başlayan kalp yetmezliği ile olan ilişkisi incelendi.
Bulgular: Toplam 262 hastanın ortalama yaşı 62.1±11.5 yıldı. Hastaların 39'u (%18.9) kadındı ve major istenmeyen
kardiyovasküler olay 73 (%28) hastada meydana geldi. Geriye dönük çok değişkenli Cox regresyon analizinde, yaş
[Hazard ratio (HR)=1.039, 95%CI:1.017-1.060, p<0.001], Killip sınıfı [HR=2.099, 95%CI:1.011-4.365, p=0.045],
serum kreatinin düzeyi [HR=2.202, 95%CI:1.247-3.811, p=0.003], ve sol atrial çapın sol ventrikül ejeksiyon
fraksiyonuna oranı [HR=1.029, 95%CI:1.019-1.038, p<0.001] major istenmeyen olayların bağımsız prediktörleri
olarak bulundu.
Sonuç: Sol atrial çapın sol ventrikül ejeksiyon fraksiyonuna oranı, akut koroner sendrom hastalarında 2 yıllık yeni
tanı kalp yetmezliği ve ölümün bağımsız prediktörleriydi. Bu yeni pratik index istenmeyen olayların öngörülmesi
için tüm hasta gruplarında daha fazla öngörü sağlayabilir.
Anahtar kelimeler: Akut koroner sendrom (AKS), Sol atriyal çap (SAç), Sol ventrikül ejeksiyon fraksiyonu (SVef),
Sol atriyal çap (SAç)-Sol ventrikül ejeksiyon fraksiyonu (SVef) oranı (SAç/SVef)
Sorumlu Yazar / Corresponding Author
Ahmet Seyda YILMAZ
Recep Tayyip Erdogan University,
Faculty of Medicine,
Department of Cardiology
53020, Rize, Turkey
E-mail: ahmetseydayilmaz@gmail.com
Geliş tarihi / Received:
05.06.2021
Kabul tarihi / Accepted:
20.08.2021
DOI: 10.35440/hutfd.948089
This manuscript was presen ted orally
with SB-148 number at the 36th Turkish
Cardiology Congress on 5 December
2020.
Çırakoğlu et al. Left atrial dimension to left ventricle ejection fraction ratio in MACE prediction
Harran Üniversitesi Tıp Fakültesi Dergisi (Journal of Harran University Medical Faculty) 2021;18(2):329-335.
DOI: 10.35440/hutfd.
948089
330
Introduction
Acute coronary syndrome (ACS) is leading cause of ad-
verse cardiovascular events globally, despite improve-
ment in modern medical and interventional treatment
options, in recent decades. Nowadays, several clinical in-
dicators have been recognized predicting prognosis in pa-
tients with ACS (1). However, easily applicable and cost-
effective indices continue to be research subject for bet-
ter outcome prediction.
Left atrium (LA), rather being an inactive cavity, has a piv-
otal role in diastole by functioning as a channel in the
early phase of and as a promoter pump in the late phase
of ventricular filling. Furthermore, the impaired atrial
function was shown to induce atrial fibrillation (AF), heart
failure, and to increase mortality. Potential determinants
of atrial myopathy were shown to be left atrial enlarge-
ment, premature atrial contractions and atrial fibrosis
(2,3). Left atrial diameter (LAd) is easily applicable, cost-
effective, and the simplest marker showing atrial remod-
eling and functions among left atrial enlargement indices.
Besides, increased LAd was found to be precipitated arte-
rial hypertension, AF, and stroke in normal population
and ACS patients (4,5).
Left ventricular ejection fraction (LVEF) is examined to
evaluate current clinical status in patients with ACS, rou-
tinely (6). However, in case of the preserved left ventric-
ular ejection fraction or atrial size, the outcome can be
undervalued than actual it is. Therefore, we postulated
that the combined usage of LAd and LVEF might augment
prognostication. For that purpose, it was aimed to exam-
ine the role of LAd to LVEF ratio (LAd/LVEF) as a novel
echocardiographic parameter in major cardiovascular ad-
verse events (MACE) prediction in ACS patients in long
term follow-up.
Materials and Methods
Study population
It was a retrospective, observational cohort study. A total
of 262 consecutive patients with cardiac symptoms were
assessed furtherly. Patients with ≥1 mm ST-elevation in
consecutive leads related to one of the major coronary
arteries’ territories on electrocardiography (ECG) were
accepted ST elevated Myocardial Infarction (STEMI) and
delivered to angiography laboratory, immediately. In ad-
dition, those with ischemic ST-segment depression, or T
wave inversion were taken blood sample for cardiac bi-
omarkers. Elevation in Troponin I/T or creatine kinase
(CK/MB) levels were considered to be non-ST-segment el-
evation myocardial infarction (NSTEMI). Patients with
abovementioned symptoms and ECG findings without
cardiac biomarker elevations were considered to be un-
stable angina pectoris (USAP) and also included in the
analysis (7,8). Any type of malignancy, pulmonary embo-
lism, history of coronary artery disease, congenital heart
disease, moderate to severe renal and liver failure, colla-
genous vascular disease, myocarditis, acute inflammatory
disease, history of cerebrovascular disease, moderate to
severe valvular cardiac disease, and all types of cardiomy-
opathies including restrictive and hypertrophic were de-
termined as exclusion criteria. Permission was obtained
from the Local Ethics Committee of Recep Tayyip Erdogan
University Ethic Committee numbered by 40465587-
050.01.04 on 24.06.2020.
Demographical and laboratory data
Detailed medical history and demographic features, and
routine blood analysis were obtained from each partici-
pant at admission and were stored in our institution’s da-
tabase. Killip class for risk classification were evaluated.
Hypertension and Diabetes Mellitus diagnosis were gen-
erated following the current guidelines (9,10). Family his-
tory presence of CAD was expressed as the development
of atherosclerotic cardiovascular disease (CVD) or death
from CVD in a first-degree relative (ie, parent or sibling)
prior to age 55 for males or 65 for females (11). Body mass
index (BMI) was obtained with the following formula:
weight/height(cm)2.
Transthoracic echocardiographic evaluation
Two-dimensional M-mode transthoracic echocardiog-
raphy was completed for all patients via the EPIQ 7C ul-
trasound system (Philips, Best, The Netherlands) at ad-
mission. LA and LV dimensions and wall thicknesses were
gained at parasternal long-axis images. LVEF was ob-
tained according to the modified Simpson’s method. The
LAd was considered as the length between the posterior
aortic valve and the rear left atrial wall in the end-systolic,
parasternal long-axis view. The LAd/LVEF was calculated
through LAd dividing by LVEF.
Selective coronary angiography
Primary PCI was performed immediately after admission
to all patients presented with STEMI. Patients with unsta-
ble angina pectoris (USAP) and NSTEMI underwent PCI by
the Judkins method urgently from the peripheral arteries.
Left anterior descending and left circumflex coronary ar-
teries were visualized at least from four different angles;
and the right coronary artery was at least two angles. Bal-
loon angioplasty was performed before coronary stenting
or stent was placed directly where eligible. Basal TIMI
(thrombolysis in myocardial infarction) flow grade was as-
sessed at first angiogram (12). All patient’s evaluation was
performed by two independent interventional cardiolo-
gists at the beginning of the investigation. All obtained
data, coronary angiography views, and results were rec-
orded in the database of ours institute.
Patients were given the loading dose of clopidogrel, ace-
tylsalicylic acid, and intravenous heparin prior to proce-
dure. Patients were taken into the intensive coronary unit
(ICU) till stabilization is ensured.
Clinical follow-up
New onset decompensated heart failure (HF) and all-
cause mortality during two years of follow-up was deter-
mined as MACE. All patients were recruited to routine
outpatient clinics on the 1st, 3rd, 6th, 12th months, and
Çırakoğlu et al. Left atrial dimension to left ventricle ejection fraction ratio in MACE prediction
Harran Üniversitesi Tıp Fakültesi Dergisi (Journal of Harran University Medical Faculty) 2021;18(2):329-335.
DOI: 10.35440/hutfd.
948089
331
second year after discharge. Echocardiographic findings,
physical examination, and laboratory data of each patient
were obtained from hospital admission records, national
databases, and direct phone calls or face-to-face inter-
views with patients or relatives of relevant patients. Typ-
ical heart failure symptoms including shortness of breath,
swelling of ankles, palpitation, weakness, and jugular ve-
nous fullness, pulmonary congestion, and peripheral
edema were assessed at these examinations. Patients
with the abovementioned symptoms and physical exami-
nation findings, and with LVEF under the 40% were ac-
cepted as congestive heart failure (CHF).
Statistical analysis
A 23.0 version SPSS software package (Inc., Chicago, IL)
was employed to analyze the obtained data. Statistical
significance was considered to be the p-value of less than
0.05. The normality assumption of data was assessed by
the Kolmogorov-Smirnov/Shapiro-Wilk’s test. Levene’s
test was used to check the homogeneity of variances.
While the mean ± standard deviation scheme was used to
represent the continuous variables, the percentages was
used to present the categorical variables. The Chi-square
or Fisher’s exact test was employed for the purpose of
comparing the categorical groups. While the 2-tailed Stu-
dent t-test was conducted for parameters that normally
distributed, Mann-Whitney U test was implemented for
the abnormally distributed continuous variables. The uni-
variate regression analysis was carried out to assess the
effects of the various variables on MACE. The variables
with unadjusted p<0.05 were considered to be confound-
ing factors and included in the backward multivariable
Cox regression analysis to reveal the independent predic-
tors of MACE. Areas under the receiver operating charac-
teristic (ROC) curve analysis was applied to estimate the
predictive values of LAd, LVEF, and LAd/LVEF. Kaplan-
Meier curve was drawn to show the LAd, LVEF, and
LAd/LVEF percentiles in predicting MACE.
Results
The study consisted of total 262 patients and 39 (14.8 %)
of them were female. MACE was defined as new-onset HF
and all-cause mortality, which was occurred in 73 (28%)
patients during two years of follow-up. Patients were se-
parated into two groups as regard to the presence of the
MACE. Patients in MACE (+) group were older (67.2±12 vs
60.1±10.6, p<0.001) and more likely to be male (20.2% vs
7.6%, p=0.021). DM and HT rates were higher (49.3% vs
37.6%, p=0.042; 69.9% vs 54.5%, p=0.016, respectively) in
patients with MACE (+). In addition, admission serum cre-
atinine level (1.13±0.43 vs 0.95±0.22 mg/dL; P<0.001) and
CRP (0.65 [0.35-1.25] vs 0.98 [0.52-2.5], P=0.018) were
higher in MACE (+) group (Table 1).
Patients with STEMI more likely to have MACE as compa-
red to patients with NSTEMI or USAP (40% vs 18.7%,
P<0.001). LAd and LAd/LVEF were higher (39.7±5.7 vs
37.2±4.3, p<0,001; 86.7±28.3 vs 69.4±16.9, p<0,001, res-
pectively) and LVEF was lower (49.1±11.3 vs 55.3±8.1,
P<0,001) in univariate analyze in patients with MACE
(Table 1).
In the backward multivarible Cox regression analysis, age
[Hazard ratio (HR)=1.039, 95% Confidence interval (CI):
1.017-1.060, p<0.001], serum creatinine [HR=2.202,
95%CI: 1.247-3.811, p=0.003], Killip class [HR=2.099,
95%CI: 1.011-4.365, p=0.045], and LAd/LVEF [HR=1.029,
95%CI: 1.019-1.038, p<0.001] were independent predic-
tors of MACE after 2 years follow up (Table 2).
The area under curve (AUC) for LAd/LVEF was 0.703 (95%
CI: 0.690–0.806, p<0.001) in predicting MACE in receiver
operating characteristic (ROC) analysis. In addition, the
AUC for Lad and LVEF were found as 0.634 and 0.663 res-
pectively in ROC analysis (Figure 1). The sensitivity and
specificity of LAd/LVEF >81.5 were 76.2% and 84.5% res-
pectively in predicting MACE.
Cumulative survival analysis of LAd, LVEF, and LAd/LVEF
were evaluated by Kaplan-Meier curves and presented in
a single graphical image including each parameter. It was
revealed that higher LAd/LVEF augmented the risk of all-
cause death more than LAd and LVEF alone (Figure 2).
Kaplan-Meier curve demonstrated that higher LAd/LVEF
increased the risk of MACE beginning from the early fol-
low up (Figure 3).
Discussion
In the current study, it was found that age, Killip class, se-
rum creatinine, and LAd/LVEF were independent predic-
tors of MACE in patients with ACS who underwent PCI af-
ter 2 years follow up. To the best of our knowledge,
LAd/LVEF has not been evaluated previously in predicting
MACE.
The attention in the LA increased in recent years thanks
to its complex property. LA takes a crucial role in the car-
diac circulation as an effective channel for pulmonary ve-
nous blood in early ventricular diastole and as pump in-
creasing ventricular filling in late ventricular diastole.
Therefore, left atrial function indicators are indirect indi-
ces of LV chamber compliance as well as LV volume (2,3).
However, diminished diastolic function was shown to be
associated with MACE in patients with ACS, it was re-
ported not to be apparent clinically in most of the cases.
For this reason, left atrial measurements such as left atrial
diameter, volume, and functions were used to be an indi-
cator of diastolic dysfunction in several studies (13–16).
M-mode echocardiography is conducted to all patients
prior to coronary intervention in clinical practice because
it is simple, cheap, non-invasive, and easily applicable
technique. Especially, in patients who can’t stand to lie in
a supine position until underwent PCI, not volume indices
but M-mode diameter measurements can be obtained
rapidly at emergent conditions. LAd obtained by M-mode
echocardiography is the simplest measurement among
left atrial function and structure parameters.
Çırakoğlu et al. Left atrial dimension to left ventricle ejection fraction ratio in MACE prediction
Harran Üniversitesi Tıp Fakültesi Dergisi (Journal of Harran University Medical Faculty) 2021;18(2):329-335.
DOI: 10.35440/hutfd.
948089
332
Table 1. Demographic, Angiographic, Laboratory and Echocardiographic Data
Variable
MACE (-)
(n=189)
MACE (+)
(n=73)
All Patient
(n=262)
p
Gender (Male)
160 (84.7)
53(72.9)
213(81.7)
0.021
Age (year)
60.1±10.6
67.2±12
62.1±11.5
<0.001
Hypertension n (%)
103(54.5)
51(69.9)
154(58.8)
0.016
Current smoker n (%)
81(42.9)
22(30.1)
103(39.3)
0.059
Hyperlipidemia n (%)
70(37)
26(35.6)
96(36.6)
0.474
Diabetes mellitus n (%)
71(37.6)
36(49.3)
107(40.8)
0.056
BMI (kg/m2) ∗
29.4 (25.9-32.8)
28.7 (25.2-34.6)
29.4 (26.1-33.2)
0.895
Previous CAD n (%)
32(17.2)
16(22.5)
48(18.7)
0.210
Systolic BP ∗
130 (120-140)
130 (110-145)
130 (120-140)
0.919
Diastolic BP ∗
80 (70-84.7)
80 (70-89)
80 (70-85)
0.506
Heart rate (bpm)
77.6±14.8
81.6±15.4
78.7±15.1
0.041
Diagnosis
USAP/NSTEMI
STEMI
126(66.7)
66(33.3)
29(39.7)
44(60.3)
155(59.7)
110(40.3)
<0.001
Killip class
1
>1
187(98.9)
2(1.1)
63(87.5)
9(12.5)
250(95.8)
11(4.2)
<0.001
Myocardial Blush
0-1
2
3
41(22%)
53(28.3)
93(49.6)
37(50%)
20(28.2)
16(22)
78(29.7)
73(27.8)
109(41.6)
<0.001
Responsible coronary artery
LAD
RCA
CX
84(44.5)
61(32.4)
43(23.1)
33(44.9)
24(33.3)
16(21.7)
117(44.6)
85(32.6)
59(22.8)
0.183
Stent length (mm) ∗
22 (18-30)
25.5 (18-32.5)
22 (18-30)
0.325
Stent diameter (mm) ∗
3 (2.75-3)
3 (2.75-3)
3 (2.75-3)
0.686
Peak CKMB (ng/mL)
66.6±89.9
116.1±113
80.5±99
<0.001
Peak Troponin (ng/mL)
20.5±20.6
31.3±20.6
23.5±21.1
<0.001
Fasting glucose (mg/dl)
143±66
167±75
150±69
0.016
Cr (mg/dl)
0.65±0.22
1.13±0.43
1.05±0.31
<0.001
CRP (mg/L) ∗
0.65 (0.35-1.25)
0.98 (0.52-2.5)
0.69 (0.37-1.3)
0.018
Hemoglobin (gr/dL)
14.3±1.8
13.8±1.9
14.2±1.8
0.088
WBC (10
3
/µL) ∗
9.7 (7.9-12)
10.1 (8-13.4)
9.8 (7.9-12.1)
0.393
ACEI / ARB
155(83)
58(79.5)
213(81.2)
0.081
ASA
187(99.2)
67(93.2)
254(96.5)
0.520
Beta blocker
131(69.5)
53(73)
184(70.2)
0.139
CCB
43(23)
14(20.1)
57(21.7)
0.165
Statin
167(88.3)
58(79.5)
265(85.8)
0.119
OAD/Insulin
67(35.3)
34(46.4)
101(38.5)
0.067
LVef
55.3±8.1
49.1±11.3
53.5±9.4
<0.001
LA diameter
37.2±4.3
39.7±5.7
37.9±4.8
<0.001
LAd/LVefr
69.4±16.9
86.7±28.3
74.2±22.1
<0.001
BMI: Body mass index, CAD: Coronary artery disease, BP: Blood pressure, USAP: Unstable angina pectoris, NSTEMI: Non-ST Elevated myocardial
infarction, STEMI: ST-Elevated myocardial infarction, LAD: Left Anterior Descending Artery, RCA: Right Coronary Artery, CX: Circumflex Artery, CK-
MB: Creatine Kinase, Cr: Creatinine, CRP: C reactive protein, WBC: White blood cell count, ACEI/ARB: Angiotensin converting enzyme inhbitor/ angi-
otensin receptor blocker, ASA: Acetylsalicylic acid, CCB: Calcium channel blocker, OAD: Oral anti-diabetic, LVef: Left Ventricle Ejection Fraction, LA:
Left atrium, LAd/LVefr: Left atrium to Left ventricle ejection fraction rate
∗Median value (25%-75% value)
Besides, LAd was found to be strongly associated with LV
hypertrophy and eccentric geometry and LA volume
measurements (17–19). Besides, the left atrial enlarge-
ment promotes blood stasis and increases the risk for AF
and stroke consequently. AF is also a well-established risk
factor for heart failure, stroke, and mortality, particularly
in patients with ACS (4). In addition, LAd was found to be
related to AF duration and arrhythmic burden and there-
fore it was suggested to being a virtuous marker for risk
stratification in patients with AF (16,17). Besides, Mo et al
showed LAd when added to CHADS-VASC score improved
the mortality and stroke prediction in patients with sick
sinus syndrome (21). With that in mind, we think that LAd
elevation might be responsible for increased MACE by
also inducing AF. In addition, LA modulates the hemody-
namic balance by secreting atrial natriuretic peptide
(ANP) respond to stretch of atrial wall. The ANP modu-
lates the counterbalance between renin-angiotensin-al-
dosterone and parasympathetic system by providing na-
triuresis and vasodilatation. Thus, left atrium was re-
garded as one of the components of neuroendocrine sys-
tem.
Çırakoğlu et al. Left atrial dimension to left ventricle ejection fraction ratio in MACE prediction
Harran Üniversitesi Tıp Fakültesi Dergisi (Journal of Harran University Medical Faculty) 2021;18(2):329-335.
DOI: 10.35440/hutfd.
948089
333
Table 2. Cox Regression Analysis for independent predictors of MACE
Univariate
Multivariate
Variable
HR
95%CI
p
HR
95%CI
p
Gender (Male)
0.525
0.313-0.879
0.014
Age (year)
1.050
1.029-1.071
<0.001
1.039
1.017-1.060
<0.001
Diagnosis
2.590
1.620-4.142
<0.001
Hypertension
1.640
0.994-2.707
0.053
Current smoker
0.877
0.680-1.130
0.309
Heart rate
1.016
1.001-1.031
0.041
Killip class
5.170
2.552-10.47
<0.001
2.099
1.011-4.365
0.045
Peak Troponin
1.020
1.009-1.031
<0.001
Fasting glucose
1.004
1.001-1.007
0.009
Diabetes mellitus
1.542
0.973-2.411
0.063
Serum creatinine
3.378
2.092-5.454
<0.001
2.202
1.274-3.811
0.003
CRP
1.075
1.012-1.141
0.018
Hemoglobin
0.897
0.801-1.005
0.061
WBC
1.055
0.978-1.138
0.166
LAd/LVefr
1.030
1.022-1.038
<0.001
1.029
1.019-1.038
<0.001
CK-MB: Creatine Kinase, CRP: C reactive protein, LA: Left atrium, LAd/LVefr: Left atrium to Left ventricle ejection fraction rate, LVEF: Left Ventricle
Ejection Fraction, WBC: White blood count.
Figure 1: Receiver operating characteristic (ROC) curves
for LAd, LAd/LVEF ratio and LVEF for predicting MACE.
(LA: Left atrial diameter, LAd/LVEF: Left atrium to Left ventricle ejection
fraction rate, LVEF: Left ventricle)
Pressure or volume overload in left atrium promote left
atrial enlargement (2,22). Therefore, we thought that LAd
might be related to MACE by this way.
The LVEF is examined at admission and during follow-up
and is also well established to be related to outcomes in
patients with ACS (6,23). Boch et al. found that LVEF has
more predictive value than other echocardiographic pa-
rameters predicting MACE in patients with ACS. In addi-
tion, in patients whose LVEF was under 48%, the mortality
rate was 3.3-fold higher (24). While in the present study,
MACE was shown to be related to decreased LVEF, it was
eliminated the predictive value of LVEF and LAd by multi-
variable regression analysis. This could be owing to the
limited number of patients or to LVEF and LAd were rela-
tively close to the normal range. On the other hand, this
could mean that left atrial enlargement or deteriorated
left ventricular systolic function might be scarce to pre-
dict future adverse events alone. In addition, in case of
elevated LAd and normal LVEF or normal LAd and de-
creased LVEF, we may need a further tool for outcome
prediction because of effects of LAd and LVEF balance
each other. Meanwhile, in the early stage of ACS, tachy-
cardia, transient ischemic dysfunction, stunning, or hiber-
nation may occur and the LVEF may show variability sub-
sequently. Therefore, the utilization of quantitative and
combined indices may provide a more objective predic-
tion of outcomes. It was shown that adding LVEF to other
scoring tools elicit more accurate results in outcome pre-
diction (24). With that in mind, we think the combined us-
age of LAd and LVEF might facilitate MACE prediction as
compared to their single usage.
Heart failure with preserved ejection fraction (HFpEF) ac-
counts for almost half of all types of heart failure. Mor-
bidity and mortality rates, and quality of life in patients
with HFpEF can be worse than with reduced ejection frac-
tion (25). It does not exist a single objective marker to de-
fine HFpEF then its diagnosis is challenging. Therefore,
these patients are evaluated by measuring diastolic pa-
rameters. HFpEF is suspected in patients with symptoms
and findings of heart failure accompanying to structural
heart diseases such as left atrial enlargement or left ven-
tricular hypertrophy (26). However, it was multisystemic
disease and might present with non-cardiac complaints.
Therefore, patients without specific signs and symptoms
of HFpEF can easily be disregarded (27).
Çırakoğlu et al. Left atrial dimension to left ventricle ejection fraction ratio in MACE prediction
Harran Üniversitesi Tıp Fakültesi Dergisi (Journal of Harran University Medical Faculty) 2021;18(2):329-335.
DOI: 10.35440/hutfd.
948089
334
Figure 2. Kaplan-Meier curves for LAd, LAd/LVEF ratio and
LVEF for MACE risk.
( LA: Left atrial diameter, LAd/LVEF: Left atrium to Left ventricle ejection
fraction rate, LVEF: Left ventricle, MACE: Major adverse cardiovascular
event)
Figure 3. Kaplan-Meier curves demonstrated that higher
LAd/LVEF ratio increased the risk of all-cause death begin-
ning from the early follow-up.
(LAd/LVEF: Left atrium to Left ventricle ejection fraction rate)
On the other hand, ACS was shown to be one of the risk
factors of HFpEF (28). Antonelli et al. showed that those
who were developed HFpEF had a 3-fold higher mortality
risk than those without heart failure among patients with
acute MI (25). Therefore, the parameters that involve
these patient groups provide more accurate evidence
about surveillance without a doubt. Moreover, LAd/LVEF
may indicate HFpEF and contribute to mortality by that
way. In addition, HFpEF was shown to be directly related
to age owing to cardiac functional and structural changes
were accelerated with increasing age (27). In this study,
age was an independent factor in the fully adjusted
model. This being the case, it can be stated that we have
revealed the underlying HFpEF patients by studying the
LAd/LVEF ratio. Therefore, this ratio can be evaluated
with further studies as a new marker in patients with sus-
pected HFpEF.
The association between renal function and cardiovascu-
lar diseases is well validated. Especially, renal dysfunction
is common comorbidity in patients with HF and ACS and
is related to short and long-term adverse outcomes
(29,30). Along similar to previous studies, we showed that
the serum creatinine predicted the MACE in patients with
ACS, independently. Renal function assessment may be
added to the prediction models of MACE in future studies.
There are various limitations to admit. It is a single-center
study conducted with heterogeneous patient groups in-
cluding relatively inadequate number of patients. Meas-
urements were made by M-mode echocardiography
which was found to be inferior compared to left atrial vol-
umetric assessment. Therefore, due to LAd does not con-
sistently indicate LA volume, the power of the present
study may be lower than would be conducted by LA vol-
ume measurements. One the other hand, simple M-mode
LA size measurements are suggested in daily clinical prac-
tice still. Lastly, LAd/LVEF ratio had relatively weak value
predicting long term MACE.
Conclusion
The significant relationship was found between the
LAd/LVEF and MACE in the present study. This new, sim-
ple, and easy applicable indices at admission and during
the follow-up in predicting adverse events would facili-
tate clinical guidance. In addition, the combination of sys-
tolic and diastolic parameters may be more logical pre-
dicting MACE due to each is associated with. Besides, this
ratio might be giving a clue about HFpEF in patients with
ACS or normal population. However, this association
should be elucidated by further studies with a large pop-
ulation.
Ethical Approval: Ethics Committee of Recep Tayyip Erdogan
University Ethic Committee numbered by 40465587-050.01.04
on 24.06.2020
Author Contributions:
Concept: MÇ, ASY
Literature Review: GÇ, ASY
Design : ÖFÇ, MÇ
Data acquisition: ASY, MÇ
Analysis and interpretation: ÖFÇ, MÇ
Writing manuscript: ÖFÇ, ASY
Critical revision of manuscript: ÖFÇ, GÇ, MÇ
Conflict of Interest: The authors have no conflicts of interest to
declare.
Financial Disclosure: This research received no grant from any
funding agency in the public, commercial or not-for-profit sec-
tors.
Çırakoğlu et al. Left atrial dimension to left ventricle ejection fraction ratio in MACE prediction
Harran Üniversitesi Tıp Fakültesi Dergisi (Journal of Harran University Medical Faculty) 2021;18(2):329-335.
DOI: 10.35440/hutfd.
948089
335
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