Circulation: Cardiovascular Interventions

ORIGINAL ARTICLE

Change in Left Ventricular Ejection Fraction

With Coronary Artery Revascularization and
Subsequent Risk for Adverse Cardiovascular
Outcomes
Raghava S. Velagaleti , MD, MPH; Joy Vetter, MA, MPH; Rachel Parker, MPH; Katherine E. Kurgansky, MPH;
Yan V. Sun , PhD; Luc Djousse , MD, DSc; J. Michael Gaziano, MD; David Gagnon , MD, PhD*; Jacob Joseph , MD*

BACKGROUND: Coronary revascularization is recommended to treat ischemic cardiomyopathy. However, the relations of
revascularization-associated ejection fraction (EF) change to subsequent outcomes have not been elucidated.

METHODS: In 10 071 veterans (mean age 67 years; 1% women; 15% non-White) who underwent a first percutaneous
coronary intervention (PCI) or coronary artery bypass grafting between January 1, 1995, and December 31, 2010, and had
prerevascularization and postrevascularization EF measured, we calculated delta-EF (postprocedure EF–preprocedure EF).
We related delta-EF as a continuous measure and as categories (≤−5, −5<delta-EF<0, delta-EF=0, 0<delta-EF<5, and
delta-EF≥5) to death (using Cox regression) and heart failure hospitalization days (using negative binomial regression) in
multivariable-adjusted models, for total sample, and PCI and coronary artery bypass grafting strata.

RESULTS: Over follow-up (mean/maximum 5/14 years) 56% died. Each 5% improvement in delta-EF was associated with
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statistically significant reductions in death and heart failure hospitalization days of 5% (95% CI, 3%–7%) and 10% (95%
CI, 5%–15%), respectively, in the total sample and 6% (95% CI, 4%–8%) and 10% (95% CI, 5%–16%), respectively, in
the PCI subgroup. Patients in the highest delta-EF category had 27% (95% CI, 19%–34%) lower mortality (30% [95%
CI, 21%–37%] lower in PCI stratum) and ≈40% lower heart failure hospitalization days in total sample and PCI stratum,
compared with those in the lowest category. Relations of delta-EF and outcomes in coronary artery bypass grafting subgroup
did not reach statistical significance.

CONCLUSIONS: Revascularization-associated EF improvement was associated with significant reductions in mortality and heart
failure hospitalization burden, particularly in the PCI subgroup.

GRAPHIC ABSTRACT: A graphic abstract is available for this article.

Key Words:  coronary artery bypass ◼ heart failure ◼ hospitalization ◼ mortality ◼ percutaneous coronary intervention

See Editorial by Tehrani and Seto

R
evascularization, particularly coronary artery bypass
grafting (CABG), is recommended for patients with
coronary artery disease (CAD) and heart failure (HF)
with reduced ejection fraction (HFrEF),1 based on the
concept that restoration of blood flow to underperfused
but viable myocardium reverses left ventricular systolic
dysfunction.2,3 An association between treatment-asso-
ciated EF improvement and outcomes has been demon-
strated with medical management in patients with HFrEF.4
However, it is unclear whether the observed benefit of

 
Correspondence to: Jacob Joseph, MBBS, MD, VA Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA 02132. Email jacob.joseph@va.gov
*D. Gagnon and J. Joseph contributed equally.
Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCINTERVENTIONS.121.011284.
For Sources of Funding and Disclosures, see page 373.
© 2022 American Heart Association, Inc.
Circulation: Cardiovascular Interventions is available at www.ahajournals.org/journal/circinterventions

Circ Cardiovasc Interv. 2022;15:e011284. DOI: 10.1161/CIRCINTERVENTIONS.121.011284 April 2022 367

 Velagaleti et al
WHAT IS KNOWN
• Surgical revascularization is usually performed to
treat coronary artery disease in patients with heart
failure and reduced ejection fraction and leads to
improved long-term survival compared with medical
management.
• However, whether ejection fraction improvement is
the mechanism mediating this benefit is still unclear.
• In addition, whether percutaneous revasculariza-
tion achieves comparable improvements in systolic
function and clinical outcomes is not established.
WHAT THE STUDY ADDS
• In patients with heart failure with reduced ejection
fraction and coronary artery disease, revascular-
ization-associated change in ejection fraction was
associated with significantly lower rates of mortality
and heart failure hospitalization burden.
• The improvements in clinical outcomes were par-
ticularly notable in those undergoing percutaneous
coronary intervention.
Nonstandard Abbreviations and Acronyms
CABG coronary artery bypass grafting
CAD coronary artery disease
EF ejection fraction
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HF heart failure
HFrEF heart failure with reduced ejection
fraction
ISCHEMIA International Study of Comparative
Health Effectiveness With Medical
and Invasive Approaches
LDL-C low-density lipoprotein cholesterol
PCI percutaneous coronary intervention
STICH Surgical Treatment for Ischemic Heart
Failure
STICHES Surgical Treatment for Ischemic Heart
Failure Extension Study
multivessel revascularization in patients with CAD and
reduced EF is mediated by an improvement in EF lead-
ing to a reduction in death and HF hospitalization, or by a
reduction in CAD events and cardiac death similar to that
seen in subjects without HF, or both mechanisms. Under-
standing the magnitude and mediating effect of revas-
cularization-associated EF improvement on subsequent
outcomes will provide a firmer evidence base in support of
revascularization in patients with CAD and HFrEF. In addi-
tion, whether percutaneous coronary intervention (PCI) is
associated with an EF improvement that correlates with
subsequent clinical outcomes has been less well studied.5
We examined the relationship between revasculariza-
tion-associated EF change and subsequent outcomes in
Circ Cardiovasc Interv. 2022;15:e011284. DOI: 10.1161/CIRCINTERVENTIONS.121.011284
EF Change With Revascularization and Clinical Outcomes
a real-world setting. We (1) quantify the magnitude of EF
improvement associated with coronary revascularization,
either with PCI or CABG and (2) elucidate the relations
of revascularization-associated EF change with subse-
quent clinical outcomes.
METHODS
Study Sample
Owing to organizational restrictions, the authors will not make
the data and study materials related to this investigation avail-
able to other researchers. The study was approved by the
Veterans Affairs Boston Healthcare System Institutional Review
Board. As the analyses were based on anonymized data from
a large preconfigured data set, informed consent was waived.
We included patients from the national Veterans Affairs patient
care databases who fulfilled the following criteria in addition to
an HF diagnosis code:
1. Underwent PCI or CABG between January 1, 1995, and
December 31, 2010
2. At least one EF measurement in the year preceding
revascularization (EF1)
3. EF1<50%
4. At least one EF measurement within the year succeeding
revascularization (EF2).
Figure 1 displays the cohort compilation process. Of all
revascularization patients considered for inclusion in this study,
≈90% had an EF measurement available within 1 year from
procedure date. The PCI and CABG procedures were identi-
fied using International Classification of Disease (Ninth Revision)
procedure codes and Current Procedural Terminology codes
(listed in Table S1). The utility and accuracy of these codes
in identifying cardiovascular procedures within the Veterans
Affairs data set have been reported.6
Exposure
EF was extracted from documents in the electronic medical
record using a natural language processing algorithm. The
methods used to create the tool7 and its validity in curating
EF-based patient groups8 have been published. During initial
development, the algorithm’s accuracy was validated by 3 inde-
pendent reviewers performing chart reviews.8 The algorithm
achieved precision of 0.986 to 1.000 for extracting EF mea-
surements.7 Details about how EF values were selected (eg,
when multiple values were available, or ranges were reported
etc) are described in Figures S1 and S2. We then calculated
delta-EF, defined as below:
Delta − EF=EF2 − EF1
Covariates
Age at the time of EF2 (the beginning of the follow-up period for
outcome assessment) was modeled as a continuous variable.
Race was categorized as White versus non-White. Information
about body mass index, systolic blood pressure, diastolic blood
pressure, LDL-C (low-density lipoprotein cholesterol), diabetes
status, smoking status (ever versus never), and serum creatinine
were obtained from clinical records. For medications, systolic
blood pressure, diastolic blood pressure, serum creatinine, and
April 2022 368
 Velagaleti et al
Figure 1. Schematic for study sample compilation.
EF indicates ejection fraction; HF, heart failure; and LVEF, left ventricular ejection fraction.
body mass index, values recorded closest to within 3 months
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on or before revascularization procedure date were used. For
LDL-C, measurements closest to within the 6-month period
before the procedure date were used. For diabetes status, a
single inpatient or 2 outpatient diagnosis codes ever recorded
on or before procedure date was categorized as yes otherwise
no. For hypertension therapy and statin therapy, if patients were
receiving treatment within the 3-month period before the pro-
cedure, they were coded yes; otherwise no.
Outcomes
Our end points of interest were as follows:
1. All-cause mortality
2. Cumulative hospitalization days for HF per year
As in our previous real-world studies, we chose cumula-
tive hospitalization days instead of number of hospitalizations
as the former has greater discriminative capacity for captur-
ing disease burden and effects of risk factors and interven-
tions.9,10 We excluded patients with any inpatient stay >180
days from the hospitalization outcome analyses. Patients
were followed from the date of EF2 measurement until death,
last Veterans Affairs visit, or the end of the follow-up period
(December 31, 2013).
Statistical Analysis
We calculated event proportions and multivariable-adjusted
event rates per 100 person-years of follow-up and event rates
by category of delta-EF, for the total sample and separately for
PCI and CABG strata. To assess the linearity of the relationship
Circ Cardiovasc Interv. 2022;15:e011284. DOI: 10.1161/CIRCINTERVENTIONS.121.011284
EF Change With Revascularization and Clinical Outcomes
between delta-EF and mortality, we fit Cox proportional haz-
ards regression cubic spline plots with delta-EF as a continu-
ous predictor of all-cause mortality (Figure 2).
Relations of delta-EF to death were evaluated using multi-
variable Cox proportional hazards regression models. To assess
the associations of delta-EF to HF hospitalization days, we
calculated incidence density ratios using negative binomial
regression models. All multivariable models adjusted for age,
sex, race, body mass index, systolic blood pressure, diastolic
blood pressure, hypertension treatment, LDL-C, statin therapy,
diabetes, smoking status, and serum creatinine. We then per-
formed the same analyses as described above, separately by
type of revascularization: PCI and CABG.
To make results practical and clinically relevant, we
performed the following secondary analyses. We grouped
patients into delta-EF categories (≤−5, −5<delta-EF<0,
delta-EF=0, 0<delta-EF<5, and delta-EF≥5) and repeated
the aforementioned multivariable regression analyses with
delta-EF categories as the exposure and the lowest delta-
EF category as the referent group. A 2-sided P value thresh-
old of 0.05 was used to ascribe statistical significance.
Analyses were performed using SAS Enterprise Guide 7.1
(SAS Institute Inc, Cary, NC).
RESULTS
Study Cohort
Baseline characteristics of the study sample are shown
in Table 1. There were some statistically significant
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 Velagaleti et al EF Change With Revascularization and Clinical Outcomes

Figure 2. Cubic spline relating delta-ejection fraction (EF) to mortality.

The spline was created using a SAS macro, specifying 9 knots placed based on Harrell’s approach, with 3 degrees of freedom, and a reference
value of no change in EF.

(but clinically modest in magnitude) differences in (median [interquartile range]) between EF1 and revascu-
baseline characteristics between the PCI and CABG larization procedure was 1 (5) days for CABG subgroup
strata. Patients who underwent PCI were older, were and 2 (9) days for PCI subgroup. The time between
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more likely to be smokers, had higher blood pressure,
higher creatinine and less likely to receive statin ther-
apy; the CABG group had a slightly higher prevalence
of diabetes.
Mean EF1 (SD) was 35 (10), and the mean follow-
up period was 5 years (maximum 14 years). The time
revascularization procedure and EF2 was 242 (236)
days for CABG stratum and 246 (231) days for the PCI
stratum. The distribution of patients across the 5 delta-
EF categories was 16%, 12%, 23%, 14%, and 34% for
the CABG stratum and 16%, 12%, 29%, 14%, and 29%
for the PCI stratum.

Table 1.  Baseline Characteristics of Study Participants

Total sample PCI stratum CABG stratum

(n=10 071) (n=7397) (n=2674) P value*
Age, y 67 (10) 67 (10) 66 (9) <0.0001

Race, % non-White 1369 (15) 981 (15) 388 (16) 0.33

Sex, % women 98 (1.0) 78 (1.1) 20 (0.8) 0.17
Body mass index, kg/m2 29.4 (5.9) 29.5 (6.0) 29.3 (5.9) 0.18
Systolic blood pressure, mm Hg 129 (22) 130 (22) 127 (21) <0.0001

Diastolic blood pressure, mm Hg 71 (12) 72 (13) 70 (12) <0.0001

Hypertension treatment, % 9794 (97) 7201 (97) 2593 (97) 0.30

LDL cholesterol, mg/dL 94 (35) 94 (35) 95 (35) 0.20
Statin therapy, % 8387 (83) 6072 (82) 2315 (87) <0.0001

Diabetes, % 5821 (58) 4225 (57) 1596 (60) 0.02

Smoking (current/former), % 8811 (88) 6502 (88) 2309 (86) 0.04
Serum creatinine, mg/dL 1.3 (1.0) 1.4 (1.0) 1.2 (0.8) <0.0001

Cells present mean (SD) for age, body mass index, systolic and diastolic blood pressure, LDL cholesterol, and serum creatinine; for
others they show number (%). CABG indicates coronary artery bypass grafting; LDL, low-density lipoprotein; and PCI, percutaneous
coronary intervention.
*For continuous variables we used ANOVA tests and for categorical variables we used χ2 tests. The tests determined if there was
a significant difference between the PCI and CABG groups.

Circ Cardiovasc Interv. 2022;15:e011284. DOI: 10.1161/CIRCINTERVENTIONS.121.011284 April 2022 370

 Velagaleti et al
Associations of Improvement in EF to
Outcomes
Results of models relating delta-EF as a continuous vari-
able to subsequent outcomes are displayed in Table 2.
Overall, a 5% improvement in EF was associated with a
statistically significant 5% (95% CI, 3%–7%) and 10%
(95% CI, 5%–15%) reduction in death and HF hospital-
ization days, respectively. Similarly, in the PCI subgroup,
each 5% improvement in EF was associated with statisti-
cally significant 6% (95% CI, 4%–8%) and 10% (95%
CI, 5%–16%) reductions in death and HF hospitaliza-
tion days, respectively. In the CABG stratum, reductions
in mortality and HF hospitalization days associated with
delta-EF were not statistically significant.
In secondary analyses, when delta-EF was modeled
as categories (Table 3), we noted that there was a sta-
tistically significant trend towards decreased mortal-
ity across groups, with patients in the higher delta-EF
categories having lower mortality compared with those
in the referent group. These results were similar in the
PCI stratum, with a 30% (95% CI, 21%–37%) lower
mortality hazards in patients within the category with the
largest delta-EF, compared with those in the referent
group. However, in the CABG stratum, trend in mortal-
ity across categories of delta-EF did not reach statistical
significance.
In analyses relating delta-EF categories to subsequent
HF hospitalization days (Table 4), we observed a graded,
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statistically significant trend for reduction in HF hospi-
talization days across the groups; those in the higher
delta-EF categories had lower HF hospitalization days
compared with the referent group. Similar results were
observed in the PCI stratum; patients with the largest
Table 2.  Crude Events Rates and Multivariable-Adjusted
Hazards Ratios and Incidence Density Ratios Relating Delta-
EF to Clinical Outcomes of Interest
HF hospitalization
Mortality days
Total sample (n=10 071) (n=9906)
  Crude event rate* 11.48 95.78
  Hazards/density ratio (CI) 0.95 (0.93–0.97) 0.90 (0.85–0.95)
PCI stratum (n=7397) (n=7264)
  Crude event rate* 12.42 105.07
  Hazards/density ratio (CI) 0.94 (0.92–0.96) 0.90 (0.84–0.95)
CABG stratum (n=2674) (n=2642)
  Crude event rate* 8.80 69.37
  Hazards/density ratio (CI) 0.97 (0.94–1.01) 0.95 (0.85–1.07)
Hazards ratios/density ratios (CIs) are from a multivariable Cox regression/
negative binomial regression models that included age, sex, race, body mass
index, systolic and diastolic blood pressures, hypertension treatment, LDL cho-
lesterol, statin therapy, diabetes, smoking, and serum creatinine. CABG indicates
coronary artery bypass grafting; EF, ejection fraction; HF, heart failure; LDL, low-
density lipoprotein; and PCI, percutaneous coronary intervention.
*For mortality, this represents deaths/100 person-years; for HF hospitalization
days, this reflects number of hospitalized days/100 person-years.
Circ Cardiovasc Interv. 2022;15:e011284. DOI: 10.1161/CIRCINTERVENTIONS.121.011284
EF Change With Revascularization and Clinical Outcomes
delta-EF had an ≈42% (95% CI, 15%–60%) lower HF
hospitalization days compared with the referent group.
We did not observe a significant trend for hospitalization
days across delta-EF categories in the CABG stratum.
DISCUSSION
In this large, hospital-based cohort of older patients with
substantial comorbidity burden and HFrEF who under-
went coronary revascularization, revascularization, espe-
cially PCI, was associated with a modest improvement in
EF and a significantly lower burden of subsequent mor-
tality and HF hospitalization days. There was a continu-
ous, graded association between improvement in EF and
reduced risk for subsequent death and HF hospitaliza-
tion days. Our results demonstrate the clinical benefit of
coronary revascularization in HFrEF as well as the role
of EF improvement in mediating the beneficial effects of
revascularization.
Many prior observational studies,11–15 meta-analy-
ses,3,16 one randomized controlled trial (STICH [Surgi-
cal Treatment for Ischemic Heart Failure17]), and its
extended follow-up study (STICHES [Surgical Treatment
for Ischemic Heart Failure Extension Study18]) evaluated
the benefit of revascularization in patients with CAD and
HFrEF. These investigations focused on clinical outcomes
alone (survival and other nonfatal cardiovascular events),
without evaluating the mediating effect of EF improve-
ment. They mostly report that revascularization leads to
better outcomes compared with medical therapy alone.
Several studies have reported similar survival with CABG
and PCI,11,14–16 especially if complete revascularization
is achieved,11,14 whereas others showed better survival
with CABG.19 A recent subanalysis of the ISCHEMIA
trial (International Study of Comparative Health Effec-
tiveness With Medical and Invasive Approaches) also
confirmed the benefit of revascularization in those with
CAD and HF with mild-moderately reduced EF.20 Other
studies focused only on quantifying magnitude of EF
improvement associated with completeness of revascu-
larization21 and evaluating the determinants of improve-
ment.22 Small prior studies also indicate that method of
revascularization does not seem to influence likelihood
of EF improvement.23 Our investigation is unique in that
it is a large, real-world cohort without exclusion of any
clinical subgroup and that we simultaneously evaluated
the magnitude of EF change associated with revascular-
ization and the relations of such EF change with risk for
subsequent clinical outcomes.
Although our study was not intended to directly
compare the effects of PCI versus CABG, the differ-
ent results observed in the PCI and CABG groups in
our study warrant discussion. Mortality after CABG is
higher in patients with CAD and HFrEF (compared with
those with normal EF), since preoperative reduced EF
is a strong risk factor for early mortality after CABG.24
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 Velagaleti et al EF Change With Revascularization and Clinical Outcomes

Table 3.  Secondary Analyses: Mortality Rates and Multivariable-Adjusted Hazards Ratios Across Categories of Delta-EF

Category 0, EF≤−5 Category 1, −5<EF<0 Category 2, EF=0 Category 3, 0<EF<5 Category 4, EF≥5
Total sample (n=10 071) n=1591 n=1221 n=2781 n=1421 n=3057 P value for trend
  No. of events (%) 1009 (63.42) 667 (54.63) 1605 (57.71) 763 (53.69) 1555 (50.87) <0.0001

  Crude event rate* 14.61 11.32 11.65 11.08 10.16 <0.0001

  Adjusted event rate* 12.74 10.46 10.46 10.24 9.39 <0.0001

  Hazards ratio (CI) Referent 0.80 (0.71–0.91) 0.77 (0.70–0.85) 0.78 (0.70–0.88) 0.73 (0.66–0.81) <0.0001

PCI stratum (n=7397) n=1154 n=903 n=2158 n=1040 n=2142 P value for trend
  No. of events (%) 809 (70.10) 534 (59.14) 1339 (62.05) 613 (58.94) 1193 (55.70) <0.0001

  Crude event rate* 16.13 12.31 12.45 12.05 10.90 <0.0001

  Adjusted event rate 14.37 11.58 11.49 11.20 10.26 <0.0001

  Hazards ratio (CI) Referent 0.79 (0.69–0.91) 0.75 (0.64–0.84) 0.75 (0.66–0.86) 0.70 (0.63–0.79) <0.0001

CABG stratum (n=2674) n=437 n=318 n=623 n=381 n=915 P value for trend
  No. of events (%) 200 (45.77) 133 (41.82) 266 (42.70) 150 (39.37) 362 (39.56) 0.13
  Crude event rate* 10.57 8.56 8.78 8.33 8.31 0.13
  Adjusted event rate* 9.19 7.83 7.83 7.93 7.51 0.13
  Hazards ratio (CI) Referent 0.83 (0.64–1.07) 0.80 (0.64–0.99) 0.85 (0.66–1.09) 0.81 (0.66–1.00) 0.13

Hazard ratios (CIs) are from a multivariable Cox regression model that included age, sex, race, body mass index, systolic and diastolic blood pressures, hypertension
treatment, LDL cholesterol, statin therapy, diabetes, smoking, and serum creatinine. CABG indicates coronary artery bypass grafting; EF, ejection fraction; HF, heart
failure; LDL, low-density lipoprotein; and PCI, percutaneous coronary intervention.
*For mortality, this represents deaths/100 person-years; for HF hospitalization, this reflects number of hospitalized days/100 person-years.

For example, in the STICH trial, 30-day mortality in the
CABG group was ≈4-fold higher compared with the
medical management group. However, in both STICH
and other CABG clinical trials, a catch-up effect has been
noted wherein long-term mortality benefit in those who
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long-term mortality benefit after CABG. Alternately, since
clinical trial patients are younger compared with real-
world patients and age strongly modifies the effect of
CABG on subsequent outcomes,25,26 it is possible that
the older age of our cohort may have contributed to the

survive the initial postoperative phase makes the overall lesser benefit of CABG. PCI, which does not have an
results in the CABG arm of the clinical trial better. Since early mortality penalty similar to CABG, may conceiv-
this effect may take several years to manifest, as evident ably be a better option in terms of harmonized risk ver-
when comparing the results of STICH and STICHES, it sus benefit in older patients with CAD and reduced EF
is possible that the mean follow-up period of 5 years in needing revascularization; in younger patients and those
our study may not have been sufficient to uncover the with a lower comorbidity burden, CABG is likely still the
Table 4.  Secondary Analyses: HF Hospitalization Rates and Multivariable-Adjusted Incidence Density Ratios Across Catego-
ries of Delta-EF

Category 0, Category 1, Category 2, Category 3,

EF≤−5 −5<EF<0 EF=0 0<EF<5 Category 4, EF≥5
Total sample (n=9906) n=1565 n=1201 n=2742 n=1391 n=3007 P value for trend
  Crude event rate* 112.10 122.05 93.36 89.90 83.09 0.0003
  Adjusted event rate* 122.71 127.68 96.43 79.86 87.22 0.0003
  Negative binomial density ratio (CI) Referent 0.99 (0.65–1.52) 0.70 (0.49–1.00) 0.65 (0.43–0.97) 0.59 (0.42–0.83) 0.0003
PCI stratum (n=7264) n=1131 n=888 n=2126 n=1014 n=2105 P value for trend
  Crude event rate* 124.27 136.53 105.85 98.00 86.32 0.0005
  Adjusted event rate* 144.69 150.93 111.65 85.48 89.67 0.0005
  Negative binomial density ratio (CI) Referent 1.07 (0.67–1.71) 0.74 (0.50–1.10) 0.66 (0.42–1.03) 0.58 (0.40–0.85) 0.0005
CABG stratum (n=2642) n=434 n=313 n=616 n=377 n=902 P value for trend
  Crude event rate* 80.24 81.89 49.22 67.44 74.99 0.63
  Adjusted event rate* 72.33 68.56 50.98 66.26 79.73 0.63
  Negative binomial density ratio (CI) Referent 0.81 (0.34–1.93) 0.62 (0.29–1.31) 0.82 (0.36–1.87) 0.78 (0.39–1.55) 0.63

Incidence density ratios (CIs) are from a negative binomial regression model that included age, sex, race, body mass index, systolic and diastolic blood pressures,
hypertension treatment, LDL cholesterol, statin therapy, diabetes, smoking, and serum creatinine. CABG indicates coronary artery bypass grafting; EF, ejection fraction;
HF, heart failure; LDL, low-density lipoprotein; and PCI, percutaneous coronary intervention.
*For mortality, this represents deaths/100 person-years; for HF hospitalization, this reflects number of hospitalized days/100 person-years.

Circ Cardiovasc Interv. 2022;15:e011284. DOI: 10.1161/CIRCINTERVENTIONS.121.011284 April 2022 372

 Velagaleti et al
preferred revascularization strategy. And last, it is pos-
sible that the mechanism mediating the benefit of CABG
and PCI is different. CABG, which reduces rates of sub-
sequent nonfatal cardiovascular events and coronary
death in patients with multivessel CAD, may be exert-
ing its beneficial effects on mortality independent of EF
improvement (eg, by reduction of fatal myocardial infarc-
tions), whereas PCI’s effect might be largely mediated
via EF improvement.
Another important observation in our investigation is
the wide interindividual variation in delta-EF. Prior studies
have also noted that postrevascularization EF improve-
ment is generally modest and variable, and a signifi-
cant number of patients have lower postprocedure EF.
This could be for various reasons. Although controversy
exists about whether revascularization decisions should
be made based on myocardial viability, prior studies do
indicate that the presence of viability predicts likelihood
of EF recovery. Another factor could be the extent of
revascularization (complete versus incomplete). The use
of invasive physiological assessment to demonstrate
flow limitation and guide revascularization may also influ-
ence likelihood of EF improvement. And last, variations in
postrevascularization medical management may explain
some of the variability of delta-EF.
The clinical implications of our findings are 2-fold. If
EF improvement is a mediating mechanism for improve-
ment in outcomes but is highly variable, this implies we
have a tremendous opportunity for patient selection,
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such that revascularization (which is expensive and car-
ries procedural risks) can be reserved for those with
higher likelihood of EF improvement and the rest treated
with guideline derived optimal medical therapy. Second,
since PCI is associated with EF improvement that seems
to translate to improved clinical outcomes and does not
require survival long enough to see a catch-up benefit
like CABG, older patients and those with higher surgical
risk may be better served with PCI.27
Limitations
We could not ascertain the specific indication for revas-
cularization. In addition, we were unable to systemati-
cally ascertain the receipt of various guideline derived
medical therapy or if there was variable intensification
of such therapy postrevascularization. Both of these
factors could have an impact on delta-EF; however, this
may not be systematically different between PCI and
CABG cohorts. We also do not have data on the severity
of CAD (eg, SYNTAX score for each patient) or extent
of revascularization (complete versus incomplete), myo-
cardial viability, or specific adjunctive procedural medi-
cations or techniques used. Advances in both medical
management and procedural and technological innova-
tions might mean that contemporary patients may be
deriving a larger, or more consistent improvement in EF
Circ Cardiovasc Interv. 2022;15:e011284. DOI: 10.1161/CIRCINTERVENTIONS.121.011284
EF Change With Revascularization and Clinical Outcomes
with revascularization compared with what we observed,
and advanced imaging modalities might provide more
precise estimates.28 The observational nature of the
study cannot completely rule out confounding despite
statistical adjustment.
Conclusions
Patients with HFrEF are at high risk for mortality and
recurrent hospitalizations. Our results demonstrate that
EF improvement after revascularization was variable but
was associated with a significant reduction in mortality
and hospitalization burden, especially after PCI. Further
research is needed to examine any differences between
PCI and CABG on EF improvement and outcomes and
to refine patient selection, such that those with the most
expected benefit in terms of EF improvement can be
offered the most appropriate method of revascularization
in addition to optimal medical therapy.
ARTICLE INFORMATION
Received July 18, 2021; accepted February 14, 2022.
Affiliations
Cardiology Section, Department of Medicine (R.S.V., J.J.) and Massachusetts
VA Epidemiology Research and Information Center (J.V., R.P., K.E.K., L.D., J.M.G.,
D.G.), VA Boston Healthcare System. Emory School of Public Health, Atlanta,
GA (Y.V.S.). Atlanta VA Healthcare System, Decatur, GA (Y.V.S.). Division of
Aging (L.D., J.M.G.) and Division of Cardiovascular Medicine (J.J.), Brigham and
Women’s Hospital, Boston, MA.
Sources of Funding
The work described in this article was partially supported by a Veterans Affairs
(VA) Merit grant 1I01CX001922-01awarded to Dr Joseph.
Disclosures
Dr Joseph reports receiving research grants from Amgen, Novartis, Kowa, Ot-
suka, NIH, and Veterans Affairs (VA). The other authors report no conflicts.
Supplemental Material
Figures S1–S2
Table S1
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