Keywords
coronary artery bypass grafting - CABG - off-pump surgery - heart failure
Introduction
Coronary artery disease (CAD) is the leading cause of death in the United States and
accounted for 13% of deaths nationwide in 2018.[1] Ischemic cardiomyopathy, with left ventricular dysfunction and heart failure may
develop over time, leading to even higher morbidity and mortality. Coronary artery
bypass grafting (CABG) has been shown to be superior to medical therapy alone or percutaneous
coronary intervention for the treatment of ischemic cardiomyopathy.[2]
[3]
Several studies have shown a recovery of left ventricular ejection fraction (LVEF)
postoperatively, attributed to increased myocardial blood flow of the revascularized
areas after CABG.[4]
[5]
[6]
[7]
[8]
[9] However, controversy exists about the temporal evolvement of LVEF recovery postoperatively
and some of the published data have shown a benefit limited only to the early postoperative
period.[10]
[11] Aim of this study is the evaluation of left ventricular systolic function recovery
in the first postoperative year in patients with ischemic cardiomyopathy undergoing
CABG.
Patients and Methods
A total of 50 patients with CAD and severe left ventricular dysfunction, defined as
an LVEF ≤35%, underwent isolated CABG in a single center in the period 2017 to 2019.
We performed a retrospective analysis of the echocardiographic and clinical follow-up
data at 3 months and 1 year postoperatively. The study was approved and individual
informed consent was waived by the local ethics committee (BASEC number: 2021-00625).
The procedure was performed over a median sternotomy in 46 (92%) patients and over
a left anterolateral minithoracotomy in 4 (8%) patients. Cardiopulmonary bypass (CPB)
was used in 17 (34%) patients, with 3 (6%) of the patients being non-electively converted
from off-pump to on-pump CABG because of intraoperative hemodynamic instability. A
total of 15 (30%) patients were operated on-pump beating-heart, without the use of
cardioplegia and 2 (4%) patients with the use of cardioplegia. Bretschneider solution
was used for myocardial protection and applied antegrade and indirectly to the ascending
aorta. Patients were cooled to 34°C in case of CABG with cardioplegic arrest, whereas
no cooling was performed in case of on-pump beating-heart CABG. CPB was established
with arterial cannulation of the ascending aorta and venous cannulation of the right
atrium. The procedure was performed without CPB (off-pump) in 33 (66%) patients.
The following patient data were collected: preoperative and intraoperative (age, gender,
arterial hypertension, dyslipidemia, smoking status, diabetes mellitus, number of
diseased coronary vessels, previous myocardial infarction, previous percutaneous coronary
intervention, chronic obstructive pulmonary disease, previous stroke, peripheral arterial
disease, chronic renal disease, use of CPB, surgery urgency, number of coronary anastomoses,
LVEF, additive EuroSCORE), in-hospital postoperative (intubation duration, intensive
care unit stay, postoperative stay, re-exploration for bleeding or tamponade, postoperative
renal replacement therapy, implantable cardioverter defibrillator [ICD] or cardiac
resynchronization therapy defibrillator [CRT-D] implantation, myocardial infarction,
stroke, and repeat revascularization), and follow-up (LVEF at 3 months and 1 year
postoperatively, ICD or CRT-D implantation, myocardial infarction, stroke, and repeat
revascularization at 1 year postoperatively). The baseline data of the patients are
presented in [Table 1]. LVEF was assessed preoperatively, at 3 months and 1 year postoperatively by transthoracic
echocardiography.
Table 1
Baseline characteristics of the patient population (n = 50)
|
Age, years
|
66 ± 8.2
|
|
Female gender
|
7 (14)
|
|
Arterial hypertension
|
46 (92)
|
|
Dyslipidemia
|
37 (75.5)
|
|
Smoker, active or ex
|
37 (75.5)
|
|
Diabetes mellitus
|
21 (42)
|
|
Coronary artery disease
|
50 (100)
|
|
One-vessel
|
0
|
|
Two-vessel
|
5 (10)
|
|
Three-vessel
|
45 (90)
|
|
Previous myocardial infarction
|
30 (60)
|
|
Previous PCI
|
12 (24)
|
|
COPD
|
4 (8)
|
|
Previous stroke
|
10 (20)
|
|
Peripheral arterial disease
|
8 (16)
|
|
Chronic renal disease
|
20 (40.8)
|
|
OPCAB
|
33 (66)
|
|
Non-elective surgery
|
22 (44)
|
|
Number of coronary anastomoses
|
3 (3–4)
|
|
LVEF, %
|
25 (20–33)
|
|
Additive EuroSCORE, points
|
8.04 ± 3.3
|
Abbreviations: COPD, chronic obstructive pulmonary disease; LVEF, left ventricular
ejection fraction; OPCAB, off-pump coronary artery bypass; PCI, percutaneous coronary
intervention.
Note: Continuous variables are reported as mean ± standard deviation or median (first
and third quartile) and categorical variables as counts and percentages, n (%).
The statistical analyses were performed with IBM SPSS Statistics for Windows, Version
27.0 (IBM Corp, Armonk, New York, United States). Categorical variables are presented
as counts (percentages) and continuous variables as mean ± standard deviation by normally
distributed data and median (first and third quartile) by non-normally distributed
data. Assessment of the normality of data distribution was performed using mainly
Q–Q plot and histogram inspection and secondarily with the Shapiro–Wilk test and the
Kolmogorov–Smirnov test. The Wilcoxon signed-rank test was used to assess for LVEF
improvement at 3 months and 1 year postoperatively. Student's t-test, Mann–Whitney's U-test, Pearson's, and Spearman's correlation were used to identify factors leading
to LVEF improvement postoperatively. All tests were two-sided and the level of statistical
significance was set at 0.05.
Results
In-hospital Outcomes
The median intubation duration was 6 (4–12) hours, the median intensive care unit
stay was 2 (1–3) days, and the median postoperative stay was 9 (8–11) days. Three
(6%) patients underwent re-exploration for bleeding or cardiac tamponade and one (2%)
patient required postoperative renal replacement therapy. A total of four (8%) patients
died during the index hospitalization. There was no myocardial infarction, stroke,
or repeat revascularization. One patient with postoperative symptomatic ventricular
tachycardia, persistent LVEF ≤35%, and non–left bundle branch block (LBBB) with QRS
duration >120 milliseconds received a CRT-D for primary prevention of sudden cardiac
death on the sixth postoperative day (epicardial left ventricular electrode already
implanted during CABG).
Follow-up Outcomes
The 3-month and 1-year follow-up data of the patients are presented in [Table 2]. There was a statistically significant median LVEF increase from baseline to 3 months
(15% [5–22%], p < 0.0001) and 1 year (23% [13–25%], p < 0.0001) postoperatively as well as from 3 months to 1 year (4% [0–10%], p < 0.0001) postoperatively. An LVEF increase ≥10% was shown in 32 (74.4%) patients
at 3 months and 30 (78.9%) patients at 1 year postoperatively. There was no myocardial
infarction and no repeat revascularization at 1 year postoperatively. A total of six
(12%) patients died in the first postoperative year. Overall, six (12%) patients received
a CRT-D, one patient during the index hospitalization and five at follow-up. Indications
for CRT-D implantation at follow-up were primary prevention of sudden cardiac death
by persistent symptomatic LVEF ≤35% and LBBB with a QRS duration >130 milliseconds
or non-LBBB with a QRS duration >120 milliseconds (four patients with LBBB and one
patient with non-LBBB). Four (8%) patients received an ICD for primary prevention
of sudden cardiac death by persistent LVEF ≤35%. The mean implantation time point
for all devices was 0.44 ± 0.33 years postoperatively. One (2%) patient had a questionable
case of transient ischemic attack, presenting with hemiparesis and hypoesthesia of
the left upper extremity, 2 days after the ipsilateral implantation of a CRT-D, with
normal findings in cranial computed tomography and almost complete regression of the
symptoms over the next 5 days and before hospital discharge.
Table 2
Follow-up data of the patient population (n = 50)
|
LVEF at 3 mo postoperatively, %
|
40 (33–48)
|
|
LVEF increase ≥10% at 3 mo postoperatively
|
32 (74.4)
|
|
LVEF at 1 y postoperatively, %
|
45 (40–51)
|
|
LVEF increase ≥10% at 1 y postoperatively
|
30 (78.9)
|
|
ICD or CRT-D implantation at 1 y postoperatively
|
10 (20)
|
|
Myocardial infarction at 1 y postoperatively
|
0
|
|
Stroke at 1 y postoperatively
|
1 (2)
|
|
Repeat revascularization at 1 y postoperatively
|
0
|
|
Mortality at 1 y postoperatively
|
6 (12)
|
Abbreviations: CRT-D, cardiac resynchronization therapy defibrillator; ICD, implantable
cardioverter defibrillator; LVEF, left ventricular ejection fraction.
Note: Continuous variables are reported as median (first and third quartile) and categorical
variables as counts and percentages, n (%).
The results of the analysis for factors affecting LVEF improvement at 3 months and
1 year postoperatively are presented in [Tables 3] and [4]. None of the assessed factors was found to be statistically significantly associated
with LVEF improvement at 3 months postoperatively. Preoperative LVEF (p = 0.033), previous percutaneous coronary intervention (p = 0.027), normal kidney function (p = 0.020), and off-pump surgery (p = 0.036) were found to be statistically significantly negatively associated with
LVEF improvement at 1 year postoperatively.
Table 3
Univariate analysis for factors affecting LVEF improvement at 3 months postoperatively
|
Variables
|
p-Value
|
|
Age
|
0.507
|
|
Female gender
|
0.987
|
|
Arterial hypertension
|
0.098
|
|
Dyslipidemia
|
0.489
|
|
Smoker, active or ex
|
0.135
|
|
Diabetes mellitus
|
0.677
|
|
Three-vessel coronary disease
|
0.283
|
|
Previous myocardial infarction
|
0.911
|
|
Previous PCI
|
0.378
|
|
COPD
|
0.981
|
|
Previous stroke
|
0.223
|
|
Peripheral arterial disease
|
0.692
|
|
Chronic renal disease
|
0.736
|
|
OPCAB
|
0.436
|
|
Non-elective surgery
|
0.737
|
|
Number of coronary anastomoses
|
0.718
|
|
LVEF
|
0.314
|
|
Additive EuroSCORE
|
0.386
|
Abbreviations: COPD, chronic obstructive pulmonary disease; LVEF, left ventricular
ejection fraction; OPCAB, off-pump coronary artery bypass; PCI, percutaneous coronary
intervention.
Table 4
Univariate analysis for factors affecting LVEF improvement at 1 year postoperatively
|
Variables
|
p-Value
|
|
Age
|
0.304
|
|
Female gender
|
0.763
|
|
Arterial hypertension
|
0.606
|
|
Dyslipidemia
|
0.642
|
|
Smoker, active or ex
|
0.110
|
|
Diabetes mellitus
|
0.976
|
|
Three-vessel coronary disease
|
0.385
|
|
Previous myocardial infarction
|
0.154
|
|
Previous PCI
|
0.027
|
|
COPD
|
0.272
|
|
Previous stroke
|
0.180
|
|
Peripheral arterial disease
|
0.680
|
|
Chronic renal disease
|
0.020
|
|
OPCAB
|
0.036
|
|
Non-elective surgery
|
0.803
|
|
Number of coronary anastomoses
|
0.356
|
|
LVEF
|
0.033
|
|
Additive EuroSCORE
|
0.816
|
Abbreviations: COPD, chronic obstructive pulmonary disease; LVEF, left ventricular
ejection fraction; OPCAB, off-pump coronary artery bypass; PCI, percutaneous coronary
intervention.
Discussion
Our data show that patients with ischemic cardiomyopathy undergoing CABG exhibit a
significant LVEF increase both in the first 3 months as well as the first year after
revascularization. LVEF recovery was markedly higher in the first 3 postoperative
months but continued further on during the first postoperative year. Previous studies
have also shown an LVEF recovery in patients with ischemic cardiomyopathy after CABG,
though the temporal trend of LVEF recovery was analyzed by only a few authors with
contradicting results. Roberts et al. have shown a transient depression of LVEF in
the first 2 postoperative hours, followed by recovery to preoperative levels at 24 hours
and significant improvement at 7 days but no further change in LVEF from 7 days to
8 months postoperatively.[11] Similarly, Lorusso et al. have shown a significant LVEF improvement prior to hospital
discharge after CABG, with gradual offset at 3 and 12 months postoperatively.[10] Other research groups were able to find a significant LVEF improvement at 1, 6,
and 12 months postoperatively,[7]
[9]
[12]
[13] while some others were able to find a significant LVEF improvement postoperatively,
though no exact follow-up time point was specified.[4]
[5]
[6]
The myocardial blood flow of revascularized areas increases significantly after CABG,
driving the recovery of regional and global left ventricular function and leading
to the observed postoperative LVEF improvement.[14] However, left ventricular function cannot recover in cases of irreversible myocardial
damage, thus recovery of contractile function can only be achieved by revascularization
of viable ischemic myocardium. Using preoperative dynamic positron emission tomography(PET)
and transmural myocardial biopsy, some authors were able to show that higher levels
of myocardial blood flow, higher myocardial glucose uptake, less tissue fibrosis,
and specific alterations of cardiomyocytes (loss of myofilaments and accumulation
of glycogen) were associated with reversible left ventricular dysfunction.[7]
[9]
[15]
[16] Other authors were able to identify patients with viable ischemic myocardium and
predict myocardial recovery by using dobutamine echocardiography, magnetic resonance
tomography with late gadolinium enhancement, and single photon emission computed tomography
(SPECT).[17]
[18]
[19]
[20] No data about preoperative myocardial viability were available in our study; therefore,
no relevant analysis could be performed.
Even though the assessment of preoperative myocardial viability with the abovementioned
imaging methods helps the prediction of left ventricular function recovery after CABG,
not all patients with evidenced viability exhibit the expected LVEF recovery. Mandegar
et al. have shown that patients with higher left ventricular end-systolic volume and
fewer viable myocardial segments in preoperative dobutamine echocardiography had a
lower likelihood of postoperative LVEF recovery.[21] Consequently, patients with poor left ventricular systolic function, severe left
ventricular dilation, and low proportion of viable myocardium are not expected to
show significant LVEF recovery after CABG. No data about preoperative left ventricular
dilation were available in our study; therefore, no relevant analysis could be performed.
Despite the overall significant LVEF improvement at 3 months and 1 year postoperatively,
every fifth patient received an ICD or CRT-D postoperatively, with an indication for
implantation based on the recommendations of international society guidelines.[22] This is a considerable proportion of patients and most probably reflects a subgroup
with a large amount of nonviable myocardium and/or severe left ventricular dilation,
who did not profit from the surgical revascularization.
This study has limitations associated with the retrospective data analysis and the
inherent patient selection bias of these analyses. Additionally, no preoperative data
about myocardial viability and left ventricular dilation were available, factors associated
with reversibility of myocardial dysfunction after CABG, which might have been able
to explain the absence of LVEF recovery in some patients.
Conclusion
In conclusion, the strengths of this study must be emphasized. Using echocardiographic
follow-up data at 3 months and 1 year postoperatively, we were able to perform an
analysis of the postoperative LVEF evolvement in patients with ischemic cardiomyopathy.
Only a few previous studies have assessed the temporal evolvement of LVEF after CABG,
with contradicting results. Our study shows a significant increase of LVEF at 3 months
and 1 year after CABG, providing more data about a continuous LVEF recovery over the
first postoperative year.
