European Heart Journal: Acute Cardiovascular Care (2021) 10, 898–908 ORIGINAL SCIENTIFIC PAPER

doi:10.1093/ehjacc/zuab058 Acute Coronary Syndromes

Prognostic impact of left ventricular ejection

fraction recovery in patients with ST-segment
elevation myocardial infarction undergoing
primary percutaneous coronary intervention:

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analysis of an 11-year all-comers registry
Oscar Otero-Garcı́a 1*, Ana Belén Cid-Álvarez1,2, Mària Juskova1,
Belén Álvarez-Álvarez1,2, Pablo Tasende-Rey1, Francisco Gude-Sampedro3,
~ a1,2, Rosa Agra-Bermejo1,2, Diego López-Otero1,2,
José Marı́a Garcı́a-Acun
Juan Carlos Sanmartı́n-Pena1, Amparo Martı́nez-Monzonı́s1,2,
Ramiro Trillo-Nouche1,2, and José R. González-Juanatey1,2
1
Cardiology Department, University Hospital Complex (CHUS), Travesı́a Choupana s/n. 15706, Santiago de Compostela, A Coru~ na, Spain; 2Biomedical Research Networking
Center on Cardiovascular Diseases (CIBERCV), Santiago de Compostela, A Coru~na, Spain; and 3Department of Clinical Epidemiology, University Hospital Complex (CHUS),
redIAPP, Santiago de Compostela, Spain

Received 6 April 2021; revised 24 May 2021; editorial decision 1 July 2021; accepted 5 July 2021online publish-ahead-of-print 29 July 2021

Aims Left ventricular ejection fraction (LVEF) recovery after an ST-segment elevation myocardial infarction (STEMI) iden-
tifies a group of patients with a better prognosis. However, the association between long-term outcomes and LVEF
recovery among patients with STEMI undergoing primary percutaneous coronary intervention (PCI) has not yet
been well investigated. Our study aims to detect differences in long-term all-cause and cardiovascular mortality be-
tween patients who recover LVEF at 1-year post-PCI and those who do not, and search for predictors of LVEF
recovery.
...................................................................................................................................................................................................
Methods This is a retrospective, single-centre study of 2170 consecutive patients admitted for STEMI in which primary PCI
and results is performed. LVEF was determined at admission and at 1-year follow-up. The primary outcomes were long-term
all-cause and cardiovascular mortality. Among the 2168 patients with baseline LVEF data, 822 (38%) had a LVEF <
50% and 1346 (62%) >_ 50%. Among those with LVEF < 50%, LVEF data at 1-year were available in 554, and 299
(54.0%) presented with complete recovery (LVEF >_ 50%). LVEF recovery was associated with a reduction in long-
term all-cause and cardiovascular mortality (P < 0.0001). Female sex, treatment with ACEIs, lower creatinine levels,
infarct-related artery different from the left main or left anterior descendent artery, and absence of prior ischaemic
heart disease were independently associated with LVEF recovery.
...................................................................................................................................................................................................
Conclusions Nearly 40% of patients with STEMI undergoing primary PCI presented with LVEF depression at hospital admission.
Among them, LVEF recovery at 1-year occurred in more than 50% and was independently associated with a signifi-
cant decrease in long-term all-cause and cardiovascular mortality.
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* Corresponding author. Tel: þ 34 981 950 751, Fax: þ 34981 950 534, Email: oscaroterogarci@gmail.com
C The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
Published on behalf of the European Society of Cardiology. All rights reserved. V
Prognostic impact of LVEF recovery in STEMI patients submitted to primary PCI 899

Graphical Abstract

↑ FEMALE

↓ PREVIOUS IHD

LVEF recovery ↓ LMCA OR LAD

↓ CREATININE
Baseli LVEF
Baseline EF ↓

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(<< 5
50%) n = 299,
54.0% ↑ ACEI
n = 822,
38% 30%

25%

Percentage of paents
No LVEF recovery
STEMI-primary
i PCI (n = 255, 46.0%) 20%
(n = 2168) 15%

10%

5%

0%
Baseline LVEF ≥ 50% Cardiovascular mortality All-cause mortality
(n = 1346, 62%) LVEF recovery Normal baseline LVEF No LVEF recovery

ACEI = angiotensin-converng enzyme inhibitors; IHD = ischemic heart disease; LAD = le
anterior descending artery; LMCA = le main coronary artery; LVEF = le ventricular ejecon
fracon; PCI = percutaneous coronary intervenon; STEMI = ST-segment elevaon myocardial
infarcon.

...........................................................................................................................................................................................
Keywords Left ventricular ejection fraction recovery • ST-segment elevation myocardial infarction • Primary percutaneous
coronary intervention • Prognosis

..
.. adverse remodelling due to necrosis, hypertrophy, inflammation,
.. and fibrosis.5–8
Introduction ..
.. The European Society of Cardiology Clinical Practice Guidelines
Left ventricular ejection fraction (LVEF) depression after an ST- .. recommend systematic echocardiographic evaluation before dis-
..
segment elevation myocardial infarction (STEMI) identifies a group of .. charge in all patients with STEMI in order to assess left ventricular
patients at increased risk all-cause and cardiovascular mortality, inde- .. function and, in those individuals with LVEF <_ 40%, the guidelines ad-
..
pendently of revascularization, with a poorer short- and long-term .. vise early re-evaluation within 6–12 weeks after discharge in order to
prognosis.1–4 .. assess the need for adopting device-based therapeutic measures.9,10
..
The improvement of LVEF in the early phase (days to months) .. Studies have described that LVEF recovery in the first weeks after
after revascularization appears to be associated with the restoration
.. an acute coronary syndrome identifies a group of patients with an
..
of coronary flow and improved myocardial ischaemia in acute occlu- .. improved prognosis (independently of revascularization and medical
sions (stunned myocardium) and/or with cell differentiation and the
.. treatment), with a lower incidence of adverse remodelling, cardiac ar-
..
recovery of normal cardiomyocyte metabolism in chronic occlu- .. rest, all-cause, and cardiovascular mortality.
sions (hibernating myocardium). In contrast, the degree of ventricu-
.. Nevertheless, the frequency of LVEF recovery and its association
..
lar functional recovery over the longer term has been related to .. with long-term outcomes in patients with STEMI undergoing primary
.
900 O. Otero-Garcı́a et al.

STEMI - primary PCI

n = 2170
2 deaths before LVEF
111 deaths during
determinaon
admission
45 deaths during 1st
year LVEF data upon admission
112 paents without n = 2168
LVEF data at 1-year

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LVEF < 50% LVEF ≥ 50%
n = 822 n = 1346

LVEF at 1-year
follow-up

LVEF ≥ 50% LVEF < 50%

n = 299 (54.0%) n = 255 (46.0%)

28 deaths 70 deaths 169 deaths

(4 CV cause) (29 CV cause) (52 CV cause)

LVEF = le ventricular ejecon fracon; STEMI = ST-segment elevaon myocardial infarcon; PCI =
percutaneous coronary intervenon

Figure 1 Flowchart of patients with STEMI undergoing primary PCI and baseline LVEF < 50% stratified by LVEF recovery at 1-year follow-up. LVEF,
left ventricular ejection fraction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

PCI has not been well investigated yet. Given the relevance of this .. with a diagnosis of STEMI subjected to primary PCI between January
..
group of patients, it is necessary to understand the benefits of LVEF .. 2008 and December 2018 were included in the study.
recovery in this population. Therefore, we sought to evaluate the .. A cohort of 2170 patients was available for inclusion, with two deaths
.. occurring before the determination of LVEF. We determined LVEF upon
prevalence of LVEF depression among patients with STEMI under- ..
going primary PCI and to test the hypothesis that patients who re- .. admission in the 2168 remaining patients, of which 1346 presented with
.. preserved LVEF (>_50%) and 822 with LVEF depression (<50%). The lat-
cover their LVEF following a STEMI have improved clinical outcomes ..
when compared with those who have persistently reduced LVEF.
.. ter group underwent repeat evaluation of LVEF at 1-year, excluding those
.. subjects who died during initial admission (n = 111), those who died dur-
Furthermore, we look for clinical parameters independently associ- .. ing the first year (n = 45), and those for whom such information could not
ated with LVEF recovery.
..
.. be obtained (n = 112). The remaining final cohort consisted of 554
.. patients. Figure 1 shows the flowchart of patients with STEMI undergoing
..
Methods .. primary PCI and baseline LVEF < 50% stratified by LVEF recovery at 1-
.. year follow-up.
..
Study population .. The demographic, clinical, echocardiographic, angiographic, and la-
A single-centre observational study was carried out, with a prospective .. boratory characteristics upon admission were entered on a prospective
inclusion of the patients in the registry and a retrospective analysis of the
.. basis in an electronic database. Left ventricular ejection fraction value at
..
prognostic usefulness of LVEF recovery at 1 year. All consecutive patients . 1-year was recorded retrospectively following a review of the reports on
Prognostic impact of LVEF recovery in STEMI patients submitted to primary PCI
..
the transthoracic echocardiographic study made in the Cardiac Imaging
Unit.
Definitions
Left ventricular ejection fraction
Both baseline and 1-year LVEF were measured echocardiographically by
the biplane Simpson method. Use was made of the cut-off point recom-
mended in the clinical practice guidelines to stratify the patients according
to LVEF upon admission: depressed LVEF (<50%) or preserved LVEF
(>_50%). This same cut-off point was established as a recovery criterion in
the re-evaluation at 1-year: non-recovered LVEF (<50%) or recovered
LVEF (>_50%). The initial LVEF value was that obtained within the first
24 h from hospital admission and always after revascularization. The value
selected for LVEF during follow-up was that closest to the first year after
the index event.
Angiographic characteristics
The infarct-related artery (IRA) was identified by the interventional cardi-
ologist who performed the primary PCI. Multivessel disease was defined
by the presence of significant lesions (>50%) in an artery other than the
IRA.
Heart failure
Data were collected on the presence of heart failure associated with the
infarction at the time of admission, considering the corresponding Killip
class.
Laboratory test values
The troponin peak was defined as the highest measured troponin I value
in ng/mL, by making use of an algorithm that consisted of repeated meas-
urements every 6 h until the maximum value was reached.
Follow-up
Follow-up was performed by reviewing the electronic case history
files of the Health Department of our autonomous community. We
reviewed the medical consultations and hospital admissions, as well
as all-cause and cardiovascular mortality. The median follow-up time
of the global patient cohort was 61 months [interquartile range
(IQR) 35–93]. The median follow-up time of the patients with initial-
ly depressed LVEF and with LVEF data at 1 year was 62 months (IQR
32–92).
Statistical analysis
Categorical variables were reported as absolute frequencies and
percentages, and comparisons were made using the chi-square test.
Continuous variables were reported as the mean ± standard devi-
ation (SD), and comparisons were made using the Student’s t-test or
Mann–Whitney U test.
The hazard functions were estimated using the Kaplan–Meier method,
while the log-rank test was used for comparison of the survival curves
(all-cause and cardiovascular mortality) between the patients that recov-
ered LVEF and those who did not. Single-variable Cox models were used
to evaluate the association between the all-time risk of death and each of
the baseline demographic and clinical variables, including LVEF recovery.
Multivariable Cox models were also constructed that, together with
LVEF recovery, included all variables that emerged as significant predic-
tors of mortality in single analyses (P < 0.05).
In order to check Cox model assumptions, the residuals method was
used (Schoenfeld residuals to check the proportional hazards
901
.. assumption, Martingale residual to assess nonlinearity, and Deviance re-
.. sidual to examine influential observations). The variance inflation factor
.. (VIF < 4) was used for diagnosing multicollinearity. The coefficients of the
..
.. regression model were used to estimate the hazard ratios (HR) and cor-
.. responding 95% confidence intervals (95% CI).
..
.. Generalized additive models for location, scale, and shape
.. (GAMLSS)11 were used to assess the influence of the following varia-
.. bles upon the LVEF value at 1 year in the patients with depressed
..
.. LVEF after primary PCI: baseline LVEF, age, sex, diabetes, arterial
.. hypertension, creatinine, prior ischaemic heart disease, involvement
..
.. of the left main coronary artery (LMCA) and/or left anterior des-
.. cendent (LAD) artery, and treatment with angiotensin-converting-
.. enzyme inhibitors (ACEIs). Based on the Akaike information criter-
..
.. ion, we finally adjusted a Box-Cox t distribution, indicated in data
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.. with a negative bias.
..
.. Data analysis was performed with R software (version 4.0.1), with free
.. access in cran-R, using the ‘survival’, ‘survminer’, and ‘gamlss’ packages.
..
..
..
.. Results
..
..
.. Results referred to left ventricular
..
.. ejection fraction at admission
..
.. Table 1 shows the baseline characteristics of the whole cohort of
.. patients stratified according to LVEF value at admission. The patients
..
.. with depressed LVEF were older, with no significant differences be-
.. tween males and females. They presented with a greater extent of
..
.. coronary disease, and a greater tendency towards two- and three-
.. vessel disease with the LAD being significantly more often the IRA.
..
.. Higher peak troponin values were also observed in these patients.
.. The patients with depressed LVEF also had a higher prevalence of dia-
..
.. betes, chronic kidney disease, and prior ischemic heart disease.
.. Concerning treatment at discharge (Table 2), the patients with
..
.. depressed LVEF received ACEIs and mineralocorticoid receptor
.. antagonists (MRAs) in a significantly greater proportion, with no dif-
..
.. ferences in the rest of drugs.
.. In the course of follow-up, we recorded a total of 274 deaths
..
.. (33.3%) in the group with depressed LVEF after the infarction vs. 169
.. deaths (12.5%) in the group with a preserved baseline LVEF. Of these
..
.. deaths, 156 (19.0%) in the patients with depressed LVEF and 52
..
.. (3.9%) in those with preserved LVEF were attributable to cardiovas-
.. cular causes.
..
.. In relation to all-cause mortality, the patients without LVEF de-
.. pression after the infarction displayed a hazard ratio (HR) of 0.47
..
.. (95% CI 0.37–0.58; P < 0.0001). After adjusting for age, sex, diabetes,
.. arterial hypertension, prior ischemic heart disease, multivessel dis-
..
.. ease, residual SYNTAX score, IRA, Killip class, troponin peak, and
.. creatinine level, the HR remained significant (HR 0.63, 95% CI 0.50–
..
.. 0.81; P < 0.0001).
.. Concerning cardiovascular mortality, the patients without
..
.. LVEF depression showed a hazard ratio (HR) of 0.19 (95% CI
.. 0.14–0.25; P < 0.0001). After adjusting for potential confounders
..
.. (age, sex, diabetes, arterial hypertension, prior ischaemic heart
.. disease, multivessel disease, residual SYNTAX score, IRA, Killip
..
.. class, troponin peak, and creatinine level), the absence of LVEF
.. depression remained a significant protective factor (HR 0.36,
..
. 95% CI 0.25–0.51; P < 0.0001).
902 O. Otero-Garcı́a et al.

Table 1 Baseline characteristics of the whole cohort of STEMI patients submitted to primary PCI relative to LVEF
category at admission

LVEF < 50% LVEF  50% P-value

(n 5 822, 38%) (n 5 1346, 62%)
....................................................................................................................................................................................................................
Demographics
Age (years) 66 ± 14 62 ± 13 <0.050
Female 200 (24.3%) 310 (23.0%) 0.490
Family history of pre-mature IHD 70 (8.5%) 150 (11.1%) 0.049
Hospital presentation
Infarct-related artery
LMCA 18 (2.2%) 4 (0.3%) <0.050

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LAD 476 (57.9%) 396 (29.4%) <0.050
Circumflex 107 (13.0%) 234 (17.4%) <0.050
RCA 199 (24.2%) 668 (49.6%) <0.050
Number of affected vessels
0 17 (2.0%) 38 (2.8%) 0.278
1 428 (52.1%) 801 (59.5%) <0.050
2 234 (28.5%) 342 (25.4%) <0.050
3 143 (17.4%) 165 (12.3%) <0.050
Number of treated vessels
0 32 (3.9%) 74 (5.5%) 0.093
1 601 (73.1%) 1013 (75.2%) 0.267
2 156 (19.0%) 211 (15.7%) 0.047
3 33 (4.0%) 48 (3.6%) 0.593
Residual SYNTAX score 3.0 ± 6.0 2.0 ± 4.0 <0.001
TIMI flow post-PCI
0 21 (2.6%) 26 (1.9%) 0.334
1 11 (1.3%) 8 (0.6%) 0.071
2 21 (2.6%) 23 (1.7%) 0.175
3 769 (93.5%) 1289 (95.8%) 0.023
Peak troponin (ng/mL) 158 ± 168 68 ± 73 <0.050
Killip class >_ 2 277 (33.7%) 203 (15.1%) <0.001
Risk factors
Diabetes 208 (25.3%) 260 (19.3%) 0.001
Hypertension 411 (50.0%) 664 (49.3%) 0.760
Dyslipidaemia 405 (49.3%) 686 (50.9%) 0.440
Obesity, BMI > 30 kg/m2 233 (28.3%) 434 (32.2%) 0.090
Current smoking 356 (43.3%) 722 (53.6%) <0.001
CKD 74 (9.0%) 68 (5.1%) <0.001
Previous IHD 113 (13.7%) 131 (9.7%) 0.004
Previous MI 81 (9.9%) 92 (6.8%) 0.012

Values are mean ± SD, n (%).

BMI, body mass index; CKD, chronic kidney disease; IHD, ischaemic heart disease; LAD, left anterior descending artery; LMCA, left main coronary artery; LVEF, left ventricular
ejection fraction; PCI, percutaneous coronary intervention; RCA, right coronary artery; STEMI, ST-segment elevation myocardial infarction.

..
Results referred to left ventricular .. LVEF recovery (LVEF >_ 50%, mean value 57%). Table 3 shows the
.. baseline characteristics of both groups. There were no differences in
ejection fraction at 1 year in patients ..
.. terms of age, though women showed LVEF recovery in a compara-
with baseline left ventricular ejection .. tively greater proportion. The patients showing LVEF recovery more
fraction depression ..
.. often corresponded to Killip Class I, with lower involvement of the
As already commented, of the 822 patients with depressed LVEF dur- .. LAD, fewer diseased vessels, and lower peak troponin values.
ing the index event, data referred to LVEF at 1 year was available for
..
.. Besides, they had a lower prevalence of chronic kidney disease and
554 (67.4%). Of these individuals, 255 (46.0%) maintained depressed .. prior ischemic heart disease. Regarding treatment at discharge, the
LVEF (LVEF < 50%, mean value 40.0%) while 299 (54.0%) showed
..
.. patients with LVEF recovery had received ACEIs in a greater
Prognostic impact of LVEF recovery in STEMI patients submitted to primary PCI 903

..
Table 2 Treatment at discharge relative to LVEF cat-
.. factors such as diabetes or arterial hypertension were not found to
.. exert an influence.
egory at admission ..
..
LVEF < 50% LVEF  50% P-value ..
(n 5 711, 35%) (n 5 1330, 65%)
.. Results referred to patients with left
..
................................................................................................. .. ventricular ejection fraction < 50% on
Statins 693 (97.5%) 1280 (96.2%) 0.080 .. admission without available
..
Aspirin 696 (97.9%) 1301 (97.8%) 0.520 .. echocardiographic data at 1 year
P2Y12 inhibitor 704 (99.0%) 1317 (99.0%) 0.990 ..
.. As we have mentioned in the Methods: Study population section,
Beta-blocker 613 (86.2%) 1117 (84.0%) 0.150 .. only 554 of the 822 patients with baseline LVEF depression under-
ACEIs 620 (87.2%) 1053 (79.2%) <0.001 ..
.. went repeat evaluation of LVEF at 1 year, excluding those subjects
MRA 280 (39.4%) 65 (4.9%) <0.001 .. who died during initial admission (n = 111), those who died during
..
.. the first year (n = 45), and those for whom such information could

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Values are n (%).
ACEIs, angiotensin-converting enzyme inhibitors; LVEF, left ventricular ejection
.. not be obtained (n = 112). In Supplementary material online, Table
..
fraction; MRA, mineralocorticoid receptor antagonist. .. S1, baseline characteristics of these 268 patients are shown and com-
.. pared with the 554 subjects with available echocardiographic data at
..
.. 1 year. Patients who died during initial admission were older, with the
proportion, with a lower frequency of MRAs. There were no signifi- .. LMCA or LAD being more often the IRA, they reached higher peaks
cant differences in the prescription of other drugs.
..
.. of troponin and presented with worse Killip class and lower baseline
During follow-up, of the 554 patients with initially depressed LVEF, ..
.. LVEF. Furthermore, diabetes and CKD were significantly present
we found 70 (27.5%) deaths in the group without LVEF recovery vs. .. more often in this group of patients. Concerning patients alive but
28 (9.3%) in the group with LVEF recovery. Of these deaths, 29 ..
.. without echocardiographic data available at 1 year, no significant dif-
(11.4%) in the group without LVEF recovery and 4 (1.3%) in the .. ferences were found neither regarding baseline characteristics nor in
group with LVEF recovery were attributable to cardiovascular ..
.. their survival status at the end of the follow-up period.
causes. ..
In relation to all-cause mortality, patients with LVEF recovery at 1 ..
..
year after the infarction displayed a hazard ratio (HR) of 0.35 (95% CI ..
0.22–0.54, P < 0.0001). Figure 2 depicts the long-term all-cause mor- .. Discussion
..
tality Kaplan–Meier curve referred to patients that recovered LVEF .. Our study, which evaluates the long-term prognostic impact of LVEF
at 1-year follow-up. After adjusting for baseline LVEF, age, sex, dia- ..
.. recovery at 1 year in a series of over 2000 consecutive STEMI
betes, arterial hypertension, prior ischaemic heart disease, multives- .. patients undergoing primary PCI, showed that LVEF recovery at 1-
sel disease, residual SYNTAX score, IRA, Killip class, troponin peak, ..
.. year post-infarction is associated with a significant decrease in all-
and creatinine level, LVEF recovery remained identified as a protect- .. cause and cardiovascular mortality. Approximately 40% of the
ive factor referred to all-cause mortality (HR 0.41, 95% CI 0.25–0.67; ..
.. patients in our series presented depressed LVEF during admission,
P < 0.0001) (Table 4). .. and 54.0% of them showed LVEF recovery at 1-year of follow-up.
Concerning cardiovascular mortality, the patients showing LVEF
..
.. Left ventricular ejection fraction depression during admission and the
recovery 1 year after the infarction showed a hazard ratio (HR) of .. persistence of depressed LVEF at 1-year of follow-up identifies a
0.12 (95% CI 0.04–0.33, P < 0.0001). In Figure 3, the long-term
..
.. group of patients with a greater all-cause and cardiovascular mortality
cardiovascular mortality Kaplan–Meier curve of patients that .. both during hospital admission and over follow-up. The patients
recovered LVEF at 1-year follow-up is shown. After adjusting for
..
.. exhibiting LVEF recovery during follow-up were predominantly
baseline LVEF, age, sex, diabetes, arterial hypertension, prior ischae- ..
.. women, with an increased frequency of IRA other than LMCA and/
mic heart disease, multivessel disease, residual SYNTAX score, IRA, .. or LAD, lower creatinine levels, and the absence of prior ischaemic
Killip class, troponin peak, and creatinine level, LVEF recovery ..
.. heart disease, compared with those patients suffering persistent
remained identified as a protective factor referred to cardiovascular .. LVEF depression. All these clinical parameters were independently
mortality (HR 0.15, 95% CI 0.05–0.44; P < 0.0001) (Table 4). ..
.. associated with LVEF recovery over follow-up. In our study, the
.. patients with LVEF recovery were more often treated with ACEIs—
..
Determinants of left ventricular ejection fraction recovery .. no significant differences being observed concerning the rest of the
at 1 year .. drugs exhibiting demonstrated prognostic benefits.
..
After 1 year of follow-up, the LVEF of the 554 patients with .. These findings reinforce the need to include the evaluation of
depressed LVEF improved from an initial mean (± SD) value of .. LVEF in the clinical follow-up of STEMI patients subjected to primary
..
40 ± 6% to 49 ± 11% (P < 0.0001). Table 5 shows the results of the .. PCI, particularly among those with depressed baseline LVEF. In add-
multivariate analysis of those variables that may influence the LVEF .. ition to being very useful for assessing the patient prognosis, the
..
value at 1-year. Baseline LVEF, female sex, and treatment with ACEIs .. evaluation of LVEF should influence the clinical monitoring strategy—
were associated with higher LVEF values at 1 year. In contrast, the in- .. stimulating patient inclusion in structured cardiac rehabilitation pro-
..
volvement of the LMCA and/or LAD, higher creatinine levels, and .. grams seeking to achieve lifestyle changes, improved control of car-
particularly prior ischaemic heart disease, were identified as poor
.. diovascular risk factors, the optimization of drug treatment, and the
..
prognostic indicators of LVEF recovery. Age and cardiovascular risk . definition of indications for the implantation of devices.
904 O. Otero-Garcı́a et al.

Table 3 Baseline characteristics among STEMI patients who had an abnormal baseline LVEF stratified by recovery to
 50% at 1-year follow-up

LVEF < 50% LVEF  50% P-value

(n 5 255, 46.0%) (n 5 299, 54.0%)
....................................................................................................................................................................................................................
Demographics
Age (years) 64 ± 13 64 ± 13 0.988
Female 38 (14.9 %) 78 (26.1%) 0.001
Family history of premature IHD 23 (9.0%) 35 (11.7%) 0.304
Hospital presentation
Infarct-related artery
LMCA 4 (1.6%) 0 (0.0%) 0.030

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LAD 176 (69.0%) 158 (52.8%) <0.001
Circumflex 23 (9.0%) 42 (14.0%) 0.067
RCA 49 (19.2%) 89 (29.8%) 0.004
Number of affected vessels
0 1 (0.4 %) 9 (3.0%) 0.021
1 128 (50.2%) 173 (57.9%) 0.071
2 79 (31.0%) 71 (23.7%) 0.056
3 47 (18.4%) 46 (15.4%) 0.340
Number of treated vessels
0 6 (2.4%) 12 (4.0%) 0.273
1 186 (72.9%) 221 (73.9%) 0.797
2 54 (21.2%) 55 (18.4%) 0.413
3 9 (3.5%) 11 (3.7%) 0.925
Residual SYNTAX score 2.5 ± 4.7 2.3 ± 4.2 0.548
TIMI flow post-PCI
0 3 (1.2%) 8 (2.7%) 0.208
1 2 (0.8%) 1 (0.3%) 0.473
2 5 (2.0%) 5 (1.7%) 0.800
3 245 (96.0%) 285 (95.3%) 0.662
Peak troponin (ng/mL) 189 ± 145 112 ± 109 <0.001
Killip class >_ 2 81 (31.8%) 62 (20.7%) 0.010
Baseline EF (%) 38 (32.0–44.0) 42 (37.0–47.0) <0.001
DEF (%) 2.2 ± 8.1 15.3 ± 7.0 <0.001
Risk factors
Diabetes 62 (24.3%) 66 (22.1%) 0.534
Hypertension 129 (50.6%) 138 (46.2%) 0.299
Dyslipidaemia 136 (53.3%) 139 (46.5%) 0.109
Obesity, BMI > 30 kg/m2 78 (30.6%) 87 (29.1%) 0.801
Current smoking 119 (46.7%) 132 (44.1%) 0.554
CKD 23 (9.0%) 11 (3.7%) 0.009
Previous IHD 56 (18.0%) 28 (9.4%) 0.003
Previous MI 35 (13.7%) 18 (6.0%) 0.002
Treatment at discharge
Statins 248 (97.3%) 295 (98.7%) 0.556
Aspirin 251 (98.4%) 291 (97.3%) 0.098
P2Y12 inhibitor 253 (99.2%) 288 (96.3%) 0.143
Beta-blocker 228 (89.4%) 266 (89.0%) 0.660
ACEIs 216 (84.7%) 277 (92.6%) 0.006
MRA 134 (52.5%) 91 (30.4%) <0.001

Values are mean ± SD, n (%).

ACE, angiotensin-converting enzyme inhibitors; BMI, body mass index; CKD, chronic kidney disease; IHD, ischaemic heart disease; LAD, left anterior descending artery; LMCA,
left main coronary artery; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist; RCA, right coronary artery; STEMI, ST-segment elevation myo-
cardial infarction.
Prognostic impact of LVEF recovery in STEMI patients submitted to primary PCI 905

..
.. ventricular dysfunction in which primary PCI was carried out. They
.. evaluated LVEF at 1 month and 6 months after hospital discharge, and
..
.. defined recovery as a 10% increment or LVEF >_ 50%. The authors
.. found that close to 50% of the patients did not meet their recovery
..
.. criteria and exhibited a poorer outcome over 5 years of follow-up.
.. This was a small historical series of patients (referred to the year
..
.. 2000) in which only 30% presented normal LVEF during hospitaliza-
.. tion, and where functional assessment was made relatively early
..
.. (maximum 6 months). The results obtained are difficult to extrapo-
.. late to a more contemporary scenario, due to differences in interven-
..
.. tional strategy and medical treatment.
.. Ndrepepa et al.,16 in a study published in the same period as the
..
.. previously mentioned article, described the evolution over time of

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.. the myocardial perfusion disorders and LVEF after 6 months in 626
..
Figure 2 Kaplan–Meier survival curve for long-term all-cause .. patients following a first infarction episode evaluated using radioiso-
..
mortality stratified by presence or absence of LVEF recovery .. topic and angiographic techniques. These authors did not specifically
(>_50%) at 1-year follow-up. LVEF, left ventricular ejection fraction. .. analyse the group of individuals with depressed LVEF but reported
..
.. that improvement of LVEF in the global series was associated with a
.. significant decrease in mortality over an average follow-up period of
..
.. three years.
Few studies to date have analysed the frequency of recovery of .. Lastly, mention must be made of the results of a recent study17
LVEF following myocardial infarction, its conditioning factors, the clin- ..
.. that analyzed the prevalence of left ventricular systolic dysfunction in
ical characteristics of the patients and its prognostic impact. The .. young patients (<50 years) with a first myocardial infarction (with
existing publications tend to include heterogeneous patient groups, ..
.. and without ST-segment elevation, and without specifying the pro-
with the assessment of systolic function after short periods of follow- .. portion of patients subjected to primary PCI), the evolution of dys-
up that make it difficult to draw solid conclusions concerning an as-
..
.. function over time, and the prognostic impact of LVEF recovery after
pect which we consider relevant not only for patient risk stratification .. 6 months vs. a group of patients with persistent LVEF depression. Of
but also particularly for the guidance of follow-up and therapeutic
..
.. the 503 patients with LVEF < 50%, follow-up data on the mentioned
optimization. .. parameter were only available in 261 cases (<50%), and of these, 90
In the Alberta Provincial Project for Outcome Assessment in Coronary
..
.. (42%) showed LVEF normalization after 6 months. After a median
Heart Disease Coronary, Chew et al.12,13 described the evolution of .. follow-up of 11 years, the patients with LVEF recovery exhibited an
LVEF in a limited number of patients with infarction (including cases
..
.. important decrease in all-cause (HR 0.12; P = 0.01) and cardiovascu-
with and without ST-segment elevation) enrolled in the global regis- .. lar mortality (HR 0.10; P = 0.025).
..
try between 2010 and 2014. Out of a total of 5964 patients, they .. Mention should be made of the observed association between
found 695 to have depressed baseline LVEF (<40% in subjects with a .. LVEF recovery and the female sex. This finding is consistent with the
..
first infarction and <45% in those with more than one), and of these, .. data from previous studies suggesting that the adjusted myocardial in-
data referred to LVEF over follow-up were only obtained in 442 .. farction outcomes are better in women than in men,18 and that
..
patients. In these subjects, only 25% showed no changes in LVEF or .. women may have a comparatively greater ischaemic myocardium re-
persistent LVEF depression, which in turn was associated with a .. 19,20
.. generative capacity.
poorer outcome. ..
A recent publication describes the prevalence and prognostic im- ..
.. Clinical implications
pact (risk of sudden cardiac death, all-cause, and cardiovascular mor- ..
tality) of changes in LVEF in infarct patients from three different .. Although the current clinical practice guidelines recommend an
.. echocardiographic study during the hospitalization of STEMI patients,
registries: REFINE (Risk Estimation Following Infarction Noninvasive ..
Evaluation), CARISMA (Cardiac Arrhythmia and Risk Stratification .. with the evaluation of LVEF, no precise recommendations are pro-
.. vided regarding the need for and timing of re-evaluation of ventricular
after Myocardial Infarction), and ISAR (Improved Stratification of ..
Autonomy Regulation).14 These are historical series of very hetero- .. function. Our findings indicate that echocardiographic evaluation at 1
.. year can help stratify patient risk and define the need for specific
geneous patients, with LVEF re-evaluation after a very short follow- ..
up period (2–8 weeks) and involving different treatment strategies.
.. therapeutic strategies, including optimization of the control of risk
.. factors and the use of drugs and devices with established prognostic
The authors themselves underscored that the heterogeneity of the ..
included patients made it impossible to perform an analysis of the
.. benefits.
..
pooled data. They found persistent LVEF depression over the follow- ..
..
up to have a negative impact on the patient prognosis. In addition, .. Study limitations
they recorded a stronger correlation to LVEF determined after .. Despite prospective patient inclusion in our primary PCI registry,
6–8 weeks than after two weeks.
..
.. some of the clinical parameters were included for analysis on a retro-
Parodi et al.15 analysed the incidence and prognostic impact of .. spective basis. On the other hand, it is possible that earlier echocar-
..
LVEF recovery in 228 patients with myocardial infarction and left . diographic assessment of all patients with depressed LVEF during
 906

Table 4 Univariate and multivariate analysis of all-cause and cardiovascular mortality among STEMI patients who had an abnormal baseline LVEF stratified by
recovery to  50% at 1-year follow-up

All-cause mortality Cardiovascular mortality

........................................................................................................... ...........................................................................................................
Univariate Multivariate Univariate Multivariate
................................................ ................................................ ................................................ ................................................
Variables HR (95% CI) P-value HR (95% CI) P-value HR (95% CI) P-value HR (I95% CI) P-value
................................................................................................................................................................................................................................................................................................
LVEF >_ 50% at 1-year 0.35 (0.22–0.54) <0.001 0.41 (0.25–0.67) <0.001 0.12 (0.04–0.33) <0.001 0.15 (0.05–0.44) 0.001
Baseline LVEF (%) 0.94 (0.93–0.94) <0.001 0.95 (0.91–0.98) 0.003 0.91 (0.89–0.92) <0.001 0.94 (0.89–0.99) 0.045
Age, years 1.07 (1.06–1.08) <0.001 1.07 (1.05 –1.09) <0.001 1.05 (1.04–1.06) <0.001 1.03 (0.99–1.06) 0.142
Female 1.75 (1.45 –2.12) <0.001 0.89 (0.52–1.50) 0.652 1.33 (0.98–1.79) 0.065 0.52 (0.17–1.65) 0.269
Diabetes 1.98 (1.63–2.39) <0.001 1.46 (0.89–2.39) 0.137 2.36 (1.79–3.13) <0.001 1.77 (0.79–3.96) 0.165
Hypertension 1.76 (1.46–2.11) <0.001 1.01 (0.65–1.58) 0.959 1.80 (1.36–2.38) <0.001 1.42 (0.65–3.11) 0.378
Previous IHD 1.51 (1.18 –1.93) 0.001 0.94 (0.55–1.60) 0.696 1.72 (1.21–2.46) 0.003 0.31 (0.09–1.16) 0.082
Multivessel disease 1.35 (1.13–1.62) 0.001 0.97 (0.61–1.54) 0.893 1.62 (1.24–2.13) <0.001 1.46 (0.63–3.37) 0.374
Residual SYNTAX score 1.08 (1.06–1.09) <0.001 1.02 (0.97–1.07) 0.535 1.09 (1.07–1.11) <0.001 1.07 (0.99–1.14) 0.085
Infarct-related artery, LMCA, or LAD 1.26 (1.05–1.51) 0.012 0.97 (0.61–1.53) 0.879 1.63 (1.25–2.14) <0.001 0.86 (0.38–1.97) 0.724
Killip class >_ 2 3.91 (3.24–4.71) <0.001 1.16 (0.73–1.85) 0.527 6.64 (5.03–8.77) <0.001 1.02 (0.46–2.25) 0.959
Creatinine at admission (mg/dL) 1.27 (1.20–1.33) <0.001 1.22 (0.92–1.61) 0.165 1.31 (1.22–1.40) <0.001 1.22 (0.86–1.73) 0.264
Peak troponin (ng/mL) 1.002 (1.001–1.003) <0.001 1.000 (0.998–1.001) 0.636 1.004 (1.003–1.004) <0.001 0.999 (0.996–1.002) 0.373

CI, confidence interval; HR, hazard ratio; IHD, ischaemic heart disease; LAD, left anterior descending artery; LMA, left main coronary artery; LVEF, left ventricular ejection fraction.
O. Otero-Garcı́a et al.

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Prognostic impact of LVEF recovery in STEMI patients submitted to primary PCI 907

hospitalization could have allowed the earlier identification of individ-

..
..
uals with persistent LVEF depression in which treatment and follow- ..
..
up could have been optimized. However, many of them had echocar- ..
diograms after shorter follow-up periods, indicated on the basis of ..
..
their clinical characteristics. Nevertheless, we only had one sched- ..
uled echocardiographic exploration after about 1 year of follow-up, ..
..
when in most cases a clinical review is made and other aspects are ..
assessed, such as the need to suspend dual antiplatelet therapy. ..
..
Mention also must be made of limitations inherent to the echocardio-
graphic determination of LVEF—though in comparison with other
imaging techniques it has demonstrated good precision in measuring
LVEF, and it is widely used in clinical research. We cannot provide
intra- and inter-observer correlation calculated as a metric of repro-
Another limitation we need to account for is the impact of the re-
gression to the mean (RTM) phenomenon on LVEF evolution. In
Supplementary material online, Figure S1, some RTM is apparent, as
subjects whose baseline results were low have tended to increase
and subjects whose baseline results were high have tended to de-
crease. However, in order to minimize this phenomenon, we
adjusted observed measurements for RTM to their baseline EF meas-
urements, and gamlss models were used to deal with non-normal dis-
.. tributions in the response variable.
.. Despite the mentioned limitations, we consider that our study has
..
.. several strengths that make it noteworthy in this field. In effect, the
.. study involves a registry with pre-specified prospective follow-up,
..
.. comprising the largest and most current cohort of STEMI patients to

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ducibility of data. Furthermore, although patients with preserved .. date—all subjected to emergency reperfusion—in which the long-
..
baseline LVEF were not the focus of the study, the fact that they .. term impact of LVEF recovery and its conditioning factors are eval-
were not assessed at 1 year for LVEF evolution needs to be recog-
.. uated. On the other hand, all the clinical information in the database
..
nized as a limitation of the study. .. was evaluated and entered by cardiologists—a fact which we believe
.. strengthens the robustness of the findings. Furthermore, the patients
..
.. in which data referred to LVEF at 1 year were not available (112
.. cases) had characteristics similar to those of the study cohort, and
..
.. the proportion of such cases was far lower than in other recent publi-
.. cations, where data referred to LVEF over follow-up were available
..
.. in less than 50% of the cases.
..
..
...
..
..
Conclusions
.. Approximately 40% of all STEMI patients undergoing primary PCI
..
.. present left ventricular dysfunction at hospital discharge. However,
.. over 50% have normalized their LVEF (>_50%) at 1-year of follow-up.
..
.. Such recovery is associated with a significant decrease in both all-
..
.. cause and cardiovascular mortality over long-term follow-up. Our
Figure 3 Kaplan–Meier survival curve for long-term
.. results suggest that re-evaluation of LVEF should be programmed
..
cardiovascular mortality stratified by presence or absence of LVEF .. during the follow-up of STEMI patients subjected to primary PCI with
recovery (>_50%) at 1-year follow-up. LVEF, left ventricular ejection .. systolic dysfunction during hospitalization, due to its prognostic and
..
fraction. .. therapeutic implications.

Table 5 Multivariate analysis of predictors of LVEF recovery at 1-year follow-up in STEMI patients submitted to
primary PCI with baseline LVEF < 50%

Variables Coefficient Standard error P-value

....................................................................................................................................................................................................................
Intercept 24.240 4.049 <0.001
Baseline LVEF 0.632 0.069 <0.001
Age (years) -0.007 0.034 0.847
Female 2.992 1.069 0.005
Diabetes -0.744 0.998 0.456
Hypertension -0.011 0.869 0.990
Creatinine at admission (mg/dL) -1.683 0.832 0.044
Previous IHD -4.504 1.207 <0.001
Infarct-related artery, LMCA, or LAD -2.515 0.870 0.004
ACE inhibitors 3.973 1.330 0.003

Box Cox t distribution; Mu link Identity; Sigma link Log (Intercept—0,170, FEVI—0,039 [0,007]; Nu link Identity (Intercept 1,439); Tau link Log (Intercept 3,204).
ACE, angiotensin-converting enzyme; IHD, ischaemic heart disease; LAD, left anterior descending artery; LMCA, left main coronary artery; LVEF, left ventricular ejection
fraction.
908 O. Otero-Garcı́a et al.

..
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Conflict of interest: none declared.
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