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\begin{document}

\title{Single versus bilateral mammary artery grafts in the setting of off-pump
coronary revascularization: Survival benefit with bilateral mammary}



\author[1]{Ana Lopez-Marco}%
\author[1]{Aidil Syed}%
\author[1]{Mabel Phillips Bn}%
\author[1]{Jennifer Williams}%
\author[1]{John Hogan Phd}%
\author[1]{Joseph George}%
\author[1]{Junaid Mansoor}%
\author[1]{Michael Ghebre Phd}%
\author[1]{Dheeraj Mehta}%
\affil[1]{Affiliation not available}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
\let\center\flushleft
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\selectlanguage{english}
\begin{abstract}
OBJECTIVE To compare postoperative and long-term results (angina,
myocardial and cerebrovascular events and coronary re-intervention)
using single versus bilateral internal mammary arteries (SIMA vs. BIMA)
in the setting of off-pump revascularisation (OPCAB) within a
single-surgeon practice. METHODS Retrospective analysis of all isolated
OPCAB performed in our institution by a single surgeon in the last 12
years.Two groups were analysed: SIMA (n = 681) and BIMA (n = 342). A
propensity score matching was performed to compare the groups, reducing
the sample to 684 patients.Follow-up (mean 6.5 \selectlanguage{ngerman}± 3.5 years) was done by
telephone interviews or clinical visits, registering also late mortality
and coronary re-intervention. Outcomes were compared to literature.
RESULTS Demographic characteristics differed between groups, with BIMA
offered predominantly to non-diabetic younger males (mean 59.4 years)
with less comorbidity. In-hospital mortality was 2\% for the SIMA group
and 1\% for BIMA (p = 0.18). Long-term mortality was also higher for the
SIMA group (2\% vs. 1\% at 1 year, p = 0.22 and 16\% vs. 5\% at 5 years,
p \textless{} 0.001). Sternal wound infection was similar in both groups
(2-3\%). Long-term follow-up revealed good freedom from angina (94\%)
with low rates of neurological and myocardial events (3\%) or need for
repeated revascularisation (3\%) in both groups. CONCLUSION BIMA offers
long-term survival benefit with similar postoperative complications.
Rates of deep sternal wound infection were comparable between the two
groups.Excellent outcomes can be achieved with OPCAB BIMA in real world
practice with adequate patient selection.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\par\null

AUTHORS:

Ana Lopez-Marco MD \textsuperscript{a}, Aidil Syed
MD\textsuperscript{a}, Mabel Phillips BN \textsuperscript{a}, Jennifer
Williams MD \textsuperscript{a}, John Hogan PhD \textsuperscript{a},
Joseph George MD \textsuperscript{a}, Junaid Mansoor
MD\textsuperscript{a}, Michael Ghebre PhD \textsuperscript{b}, Dheeraj
Mehta MD \textsuperscript{a}.

INSTITUTIONS AND AFFILIATIONS:

Department of Cardiothoracic Surgery \textsuperscript{a}, University
Hospital of Wales, Cardiff (United Kingdom)

Department of Biostatistics \textsuperscript{b}, University Hospital of
Leicester, Leicester (United Kingdom)

MEETING PRESENTATION:

This material was presented at the AATS International Coronary Congress,
November 2016, New Delhi.

CORRESPONDING AUTHOR

Miss Ana Lopez-Marco

University Hospital of Wales

Heath Park, Cardiff CF14 4XW (Wales, United Kingdom)

Tel: (+44) 029 2074 2944; Fax: (+44) 029 2074 5439

E-mail: analopez1000@hotmail.com

No funding was received for this study. No conflict of interest with
industry to declare.

\emph{INTRODUCTION}

The use of bilateral arterial mammary (BIMA) compared to single internal
mammary artery (SIMA) in coronary revascularization has been suggested
to improve long-term survival by several observational studies and
meta-analysis. \textsuperscript{{[}1-10{]}}

However, the only randomized control trial evaluating the long-term
survival with BIMA has not proved any survival benefit with the used of
BIMA. \textsuperscript{{[}11-15{]}}

On the other hand, the routine use of BIMA is still limited by the
higher morbidity and mortality associated with the technique, especially
related to deep sternal wound infection (DSWI).\textsuperscript{{[}19,
20{]}}

The objective of this study was to compare the operative and long-term
outcomes of patients using BIMA versus SIMA in the setting of off-pump
coronary bypass surgery (OPCAB) in a single institution; all cases were
undertaken by a single surgeon with experience in OPCAB surgery (over
1500 cases) whose default approach to surgical coronary
revascularization is OPCAB.

\emph{MATERIAL AND METHODS}

\textbf{Patient selection and data collection}

We conducted a retrospective analysis of prospectively electronically
collected data of all patients who underwent isolated OPCAB in our
center between 2003 and 2014. All cases were performed by the same
surgeon. Preoperative characteristics, cardiovascular risk factors,
postoperative complications and in-hospital mortality were prospectively
recorded in our database Patients Administration and Tracking System
(PATS).

Long-term follow-up was undertaken through clinical visits and/or
telephone interviews to determine clinical status (functional class and
residual angina), myocardial and cerebrovascular events and need for
repeated revascularization. The follow-up data collection was undertaken
between January and September 2016, with the majority being through
telephone interview, as patients had already been discharged from the
hospital follow-up system. Mortality data was obtained from the National
Demographic Census.

The data used in this study was approved by the institutional review
board, which deemed an individual consent form was not needed since no
patient identifiable information was used.

\textbf{Operative technique:}

OPCAB is the default technique used by the author for isolated coronary
revascularization, including emergency referrals. Surgical access was
obtained through standard median sternotomy. The revascularization
strategy for the SIMA group included LIMA-LAD and saphenous vein grafts
(SVG) for the other targets. In the BIMA group, a LIMA-RIMA T graft was
used in the majority of cases (88\%) for the left-sided lesions; a free
RIMA was used only in 12\% of the cases. A radial artery (RA) was used
as a third arterial conduit in 67 patients (20\%), most commonly for the
right-sided lesions, but in 16 cases was used for obtuse marginal
territories.

The choice of conduits was decided upon patient baseline characteristics
and anatomy and severity of the lesions. In general, BIMA is offered to
young individuals (\textless{} 65 years old) with no more than 2
comorbidities out of diabetes, COPD and obesity.

LIMA was harvested following the semi-skeletonized technique whereas a
fully skeletonized RIMA was preferred due to its optimized length and
also to preserve some vascularization of the sternum. SVG was harvested
either open or endoscopically, depending on availability of the
appropriate trained personnel and resources.

OPCAB strategy included routine opening of the right pleura to allow
mobilization of the heart during the lateral wall exposure, placement of
a deep pericardial string to facilitate the mobilization of the heart
and use of a stabilizer (Maquet Acrobat\selectlanguage{ngerman}\textsuperscript{®} or Medtronic
Octopus\textsuperscript{®}). Distal anastomoses were performed with
temporary proximal vessel occlusion was undertaken to facilitate
arteriotomy and intracoronary shunt insertion, following which vessel
flow was restored and the distal anastomosis performed, with a bloodless
field facilitated with a CO\textsubscript{2} blower (Maquet AXIUS Blower
Mister\textsuperscript{®}).

Proximal anastomoses, where necessary, were performed using either a
partial occlusion aortic clamp or Heartstring Proximal Seal System
(Maquet\textsuperscript{®}) where avoidance of aortic clamping was
indicated.

The standard sequence of anastomoses consisted of distal anastomoses on
the anterior wall (LAD, Diagonal), distal anastomoses on the inferior
wall (RCA, PDA, LV branch), followed by proximal anastomoses (if
applicable) and finally, anastomoses on the lateral wall (Intermediate,
OM). If BIMA was used, the T-graft between LIMA-RIMA was constructed
first and patency of the anastomosis tested.

\textbf{Statistical methods:}

Continuous variables were expressed as mean ± standard deviation (SD) or
median ± inter-quartile range (IQR) (depending on distribution of data)
and comparison between groups was performed using t test/ Mann-Whitney
test. Categorical variables were expressed as percentages and compared
using Chi-square/Fisher exact test as appropriate.

A multiple logistic regression model was used to identify the predictors
of early mortality and Cox regression was applied to identify the best
predictors of late mortality including all the significant variables
listed in annexed tables (cut-off at p \textless{} 0.05) (Tables 1-5).
The results were expressed as odds ratios (OR) and hazard ratios (HR)
with corresponding 95 \% confidence intervals (CI).

As the two groups were significantly different with respect to their
baseline characteristics, propensity score matching (with a match
tolerance of 0.05) was performed (including the preoperative
characteristic except echocardiographic parameters) using SPSS. The
matched groups were analyzed using the methods described above.

Kaplan-Meier survival analysis was applied; curves were built for each
group and were compared using the log-rank statistic.

SPSS 22.0 was used to analyze the data.

\textbf{Definitions:}

Previous neurologic disease: Cerebrovascular accident (CVA) or transient
ischemic attack (TIA) diagnosed before the operation, with or without
residual deficits.

Postoperative neurological events: new focal deficit after surgery;
either TIA or CVA.

Long term ventilation: postoperative ventilation for more than 7 days,
including reintubation or tracheostomy.

Respiratory complications: acute distress respiratory syndrome (ARDS) or
pneumonia during the postoperative period.

Gastrointestinal (GI) complications: bowel ischemia, GI bleeding or
laparotomy for any cause during the postoperative period.

Good LV: Ejection Fraction \textgreater{} 50\%.

Fair LV: Ejection Fraction 30 -50\%.

Poor LV: Ejection Fraction \textless{} 30\%.

\emph{RESULTS}

Between 2003 and 2014 a total of 1210 patients underwent OPCAB in our
institution under the same surgeon. One-vessel disease and other
revascularization strategies different to SIMA or BIMA were excluded. We
identified 1023 patients who fulfilled the inclusion criteria, 681 of
them in the SIMA group and 382 in the BIMA group. As the two groups were
significantly different with respect to their baseline characteristics,
propensity score matching (with a match tolerance of 0.05) was
performed, reducing the cohort to 684 patients.

BIMA was offered to younger patients (mean age 59.4 ± 9.1 vs. 69.4 ± 7.7
for the SIMA group, p = 0.001), predominantly male (91\% vs. 78\%, p =
0.001) and with less comorbidities such as diabetes (21\% vs. 32\%, p =
0.001), chronic obstructive respiratory disease (COPD, 10\% vs. 17\%, p
= 0.002), previous neurological disease (5\% vs. 10\%, p = 0.001),
peripheral vascular disease (10\% vs. 19\%, p = 0.001) or previous
myocardial infarct (45\% vs. 55\%, p = 0.005). Obesity (BMI
\textgreater{} 30) was similar in the two conduit strategies (40\% vs.
44\%, p = 0.07).

After the propensity matching, the baseline characteristics were
comparable, although age remained significantly lower in the BIMA group
(59.4 ± 9.1 vs. 69.5 ± 7.9, p = 0.001). (Table 1) Rest of the
preoperative characteristics for the non-matched and matched groups are
listed in Table 1.

Revascularisation with BIMA was used for elective cases but also
in-house urgent referrals (41\%) and emergency cases (2\%). Twenty-three
patients had an intra-aortic balloon pump (IABP) inserted before the
operation for unstable angina, and BIMA strategy was offered to three of
them. After the propensity matching, the timing for surgery and use of
preoperative IABP were also comparable. (Table 2)

The choice of conduits was not influenced by the extent of the disease.
As determined by the preoperative coronary angiogram, the use of SIMA or
BIMA was equivalent for three vessels disease (83\% vs. 80\%, p = 0.18),
two vessels disease (17\% vs. 20\%, p = 0.18) and left main stem (LMS)
disease (32\% vs. 37\%, p = 0.11). However, BIMA was most frequently
used for patients with normal left ventricular ejection fraction (LVEF)
(71\% vs. 56\%, p = 0.001) and less frequently in those in with impaired
LVEF (Fair LVEF 27\% vs. 38\%; Poor LVEF 2\% vs. 6\%, p \textless{}
0.05). (Table 2). LVEF was also included in the propensity score
matching, however the use of BIMA continued to seem to be preferred in
patients with good LVEF and an adjusted Cox analysis was conducted to
analyse the impact on survival. (Table 2)

Mean number of distal anastomoses performed was equivalent in the two
groups, even before matching (SIMA 3.7 ± 0.8 (1 - 5), BIMA 3.7 ± 0.8 (2
- 6), p = 0.11). As expected, the number of arterial conduits used was
superior in the BIMA group (2.8 ± 0.6 (2 - 5)) when compared to the SIMA
group (1.1 ± 0.3 (1 - 2), p = 0.001; note that the patients recorded as
two arterial conduits in the SIMA group had a sequential graft with the
LIMA to the LAD and first diagonal). Venous conduits were more commonly
used in the SIMA group (2.5 ± 0.8 (0 - 4) vs. 0.8 ± 0.8 (0 - 3) in the
BIMA group, p = 0.001). A third arterial conduit (RA) was used in 67
cases (20\%). Total arterial revascularization was achieved in 109 cases
(42\%). (Table 3)

Complete revascularization was achieved in 99.4\% of the cases; in the
remaining 0.6\%, a vessel (PDA or OM) was deemed to be too small to be
grafted during the intraoperative analysis. The rate of conversion from
OPCAB to ONCAB during the same period of the study was 0.7\% (8 cases,
which were excluded from the study). Reasons for conversion were:
ventricular arrhythmias (4 cases), intraoperative cardiac arrest (2
cases) or difficult exposure of an intramyocardial OM vessel (2 cases).

\textbf{In-hospital results}

The results analyzed correspond to the matched groups. The non-matched
group results are displayed in the corresponding tables but are not
commented in the manuscript.

Overall in-hospital mortality was 1.3\% (9 cases). The cause of death
was: cardiac (4 cases, 44\%), sepsis (3 cases, 34\%), neurological (1
case, 11\%), and respiratory (1 case, 11\%). In-hospital mortality was
similar in the two groups: SIMA 2\%, BIMA 1\% (p = 0.18). (Table 4)

The multivariate regression model identified previous hemodialysis (p =
0.02, OR 0.03, CI 95\% 0.1-0.5) as risk factor for in-hospital
mortality.

Complications in the immediate postoperative period were equivalent in
the two groups, except for neurological complications (1\% vs. 0\%, p =
0.05) and leg wound infection (4\% vs. 1\%, p = 0.001), which were
significantly higher in the SIMA group (Table 4). The incidence of DSWI
was only 2\% (17 patients) and was equivalent in the two groups. Of
those, 10 patients were treated conservatively and, only 7 (1\%)
required reoperation for wound debridement and/or resuturing. (Table 4)

Postoperative neurological complications (p = 0.002, OR 8.9, CI 95\% 5.1
-- 13.8) and postoperative hemofiltration (p = 0.001, OR 36.9, CI 4.9 --
27.6) were identified by the multivariate regression model as risk
factors for in-hospital mortality.

\textbf{Follow-up results}

Long-term mortality was obtained from the National Demographic Census
with a 100\% completion of data. Overall, 13\% of the patients died
during the follow-up period. The causes of death were as follows:
Cardiac 35\%, Neurological 13\%, Cancer 8\%, Renal 7\%, Respiratory 7\%,
Sepsis 6\%, Vascular 1\%, Gastrointestinal 1\% and Other 7\%. We were
unable to identify the cause of death in 15\% of the cases.

Overall one-year mortality was 2\%. It was 2\% in the SIMA group and 1\%
in the BIMA group (p = 0.22). Overall five-year mortality was 10\% and
in this case it was significantly higher in the SIMA group (16\% vs.
5\%, p \textless{} 0.001). (Table 5)

Age (p = 0.001, HR 1.1, 95\% CI 1.1 -- 1-2), COPD (p = 0.004, HR 2.0,
95\% CI 1.2-3.2) and Logistic EuroScore (p = 0.002, HR 1.0, 95\% CI 1.1-
1.2) were identified by the Cox regression as risk factors for long-term
mortality.

Mean survival calculated by the Kaplan-Meier curve was 11.0 ± 0.2 years
(95\% CI 10.7 -- 11.4) in the BIMA group and 10.0 ± 0.3 years (95\% CI
9.5 -- 10.6) in the SIMA group.

The Kaplan-Meier survival curves and number of patients at risk for each
period are displayed in Figure 1 and annexed table. The survival curve
for the non-matched population is displayed in Figure 2.

Since the two groups still differed in age, with the BIMA group having
significantly younger patients, a Cox model was applied to account the
age difference. Subjects who received BIMA still had better survival
compared to those who received SIMA (HR 0.63 (0.4 -- 0.99), p 0.047).

The Cox analysis was also applied to the LV function subgroups, as they
remained significantly different after the propensity matching. BIMA
conferred a survival benefit for patients with good LVEF (HR 0.31 (0.18
-- 0.54), p = 0.0001) and fair LVEF (HR 0.54 (0.3 -- 0.99), p = 0.048),
but we did not demonstrate a significant survival benefit when using
BIMA for patients with poor LVEF (HR 1.61 (0.27 -- 9.59, p = 0.6).

The follow-up visits and/or telephone interview revealed an excellent
functional class years after the operation. Only 8\% of the patients
reported residual angina being in CCS class II - III and 4\% of the
patients described dyspnea in NYHA Class III-IV, which was more likely
attributed to concomitant aortic stenosis or advanced COPD. The
incidence of myocardial and cerebrovascular events during the following
years after the operation was 3\%. There were no differences in the
distribution of the complications or residual symptoms amongst the
groups.

Thirty-two patients (6\%) were lost to follow-up. (Table 6)

Thirty-nine patients (7\%) underwent a repeated angiogram years after
the operation. The most common reason was residual angina, although 20\%
of them were done as part of the preoperative workup due to severe
aortic stenosis.

The angiogram confirmed patent grafts in 36\% of the cases. Graft
failure was reported in 33\% cases (13 patients), most commonly due to
the SV graft failure (62\%, 8 cases) but arterial grafts were also
affected (LIMA 15\%, 2 cases; RIMA 15\%, 2 cases; RA 8\%, 1 case). Two
patients showed combination of venous and arterial graft failure. In 8\%
of the cases (3 patients), the angiogram showed progression of the
native disease in vessels not previously grafted, and in 15\% of the
cases (6 patients) we were not able to determine the result since the
angiogram was not performed in our institution but in a local hospital.

Only 17 patients (5\%) required further revascularization with PCI, and
only 0.4\% of them were required during the first year after the
operation. (Table 6)

\emph{DISCUSSION}

Several observational studies and meta-analysis have reported the
survival advantage when using BIMA compared to SIMA, even in diabetics
and elder populations.\textsuperscript{{[}1-8{]}} The survival advantage
seems to increase through the postoperative years, even beyond 15
years.\textsuperscript{{[}9-10{]}} These studies have also reported
equivalent results in terms of mortality and morbidity after the use of
BIMA when compared to SIMA, therefore raising the question of why the
routine use of BIMA is not standard practice.

Our study confirmed the survival advantage of BIMA compared to SIMA and
the absence of extra complications or in-hospital mortality excess when
the BIMA is used.

The only RCT to date, the Arterial Revascularization Trial (ART), which
reported recently their 10-years results has not been able to
demonstrate a survival benefit with the use of BIMA at one, five or ten
years. Our mortality result using BIMA is significantly lower that the
results reported in the ART trial (1\% vs. 2.5\% at 1 year and 5\% vs.
8.7\% at 5 years).\textsuperscript{{[}11-13{]}}

They also reported a repeated revascularization rate of 1.8\% at
one-year for the BIMA group and 1.3\% for the SIMA
group.\textsuperscript{{[}11-13{]}} We have demonstrated a lower
repeated revascularization rate, especially at one-year (0.4\%), which
is even more impressive if we take on account that we are reporting
OPCAB surgery, which has always had slightly higher rates of reported
repeated revascularization (1.4\% at one-year in the CORONARY trial,
4.6\% at one-year in the ROOBY trial).\textsuperscript{{[}25, 26{]}}

A subanalysis of the ART comparing 5-years outcomes of the two
revascularization strategies used in their trial (ONCAB and OPCAB) did
not demonstrate any significant differences between the two of them.
They report 8\% five-year mortality for both strategies, while we
reported an overall 5-year mortality of 10\%, significantly higher in
the SIMA group (16\% vs. 5\%, p \textless{}
0.001).\textsuperscript{{[}15{]}}

One of the main limitations for the routine use of BIMA has been the
high reported rate of DSWI. In our study, the incidence of DSWI was only
2\%. The incidence of sternal reconstruction in our series was only 1\%,
lower than the ART study, that reported a 1.9\% sternal wound
reconstruction in the BIMA group and 0.6\% in the SIMA group at
one-year. Our lower rates are consistent with the lower rates of DSWI
expected for patients undergoing BIMA harvesting in the OPCAB
setting.\textsuperscript{{[}11-16{]}}

It has been reported that the skeletonized technique reduces the risk of
DSWI without compromising the long-term graft
patency.\textsuperscript{{[}16{]}} The ART trial suggested, that the use
of bilateral skeletonized BIMA has the same risk of DSWI than a pedicle
SIMA.\textsuperscript{{[}12{]}} Our strategy for harvesting mammary
arteries consists on semi-skeletonize the LIMA and completely
skeletonize the RIMA.

The optimal configuration of BIMA grafts is unknown. A number of
grafting strategies have been described, including bilateral grafts in
situ, use of the RIMA as a free graft from the aorta and the creation of
T or Y composite grafts from the LIMA. None of them seem to be superior
in terms of survival or long-term patency.\textsuperscript{{[}17,18{]}}

In our center, the initial use of free RIMA has declined in favor of the
current strategy of T composite grafts between LIMA and RIMA.

The routine use of BIMA is still very limited. Despite the clear
survival benefit and the equivalent in-hospital complications, it is not
offered to all patients. Some advocated reasons are the technical skills
required for harvesting and grafting, the increased operating time and
resources, the lack of consensus for selection of patients whom can
benefit most and the higher rate of DSWI.

In our institution, we believe that the technical aspects can be taught,
and we include them in our training program. However, the lack of
consensus for selection criteria is important and at present, we only
offer BIMA to certain patients based on the individual surgeon's own
selection criteria.

The use of the radial artery (RA) is still generating debate. Several
studies had tried to compare it to BIMA. A meta-analysis confirmed the
survival benefit of the BIMA also versus
SIMA-RA.\textsuperscript{{[}21{]}} On the other hand, a similar benefit
to BIMA when using a SIMA-RA composite but obviously, eliminating the
extra risk of DSWI has also been recently
reported.\textsuperscript{{[}22{]}}

Furthermore, when analyzed as a third arterial conduit, the use of a RA
has not shown to add any survival benefit. \textsuperscript{{[}23,
24{]}}

In our study, the radial artery was used only in 20\% of the cases,
mostly in the initial years of the study. The current practice of the
author is to use the BIMA for the left-sided lesions and a SV conduit
for the right-sided lesions, reserving RA for when there are no other
conduits available.

Our study has the limitations of being retrospective and purely
descriptive. We report a single surgeon experience with a level of
expertise reflected in a greater number of distal anastomoses and lower
rate of conversion and incomplete revascularization compared to the
historical OPCAB RCTs, but with the uncertainty of the feasibility of
extrapolating these results to other surgical practice.

\emph{CONCLUSIONS}

We conclude, from our results, that the use of BIMA in coronary
revascularization offers a long-term survival benefit compared to SIMA,
and that the use of BIMA does not increase the rate of postoperative
complications, including deep sternal wound infection.

Excellent outcome can be achieved with OPCAB BIMA in real world practice
with adequate patient selection.

\emph{4. BACK MATTER}

\emph{4.1. Authors contributions}

Lopez-Marco A and Mehta D made substantial contribution to conception
and design of the study. The data acquisition was performed by
Lopez-Marco A and Syed A. Phillips M, Williams J, George J, Hogan J and
Mansoor J contribution consisted on conducting the follow-up interviews
and collecting that pertinent data. The data analysis and interpretation
was done by Lopez-Marco A, along with the expertise of the statistician
Ghebre M.

\emph{4.2. Financial support and sponsorship}

No funding was received for this study. No conflict of interest with
industry to declare.

\emph{4.3. Conflicts of interest}

All authors declare that there are no conflicts of interest.

4.4. EthicaThis study was approved by the institutional Health Board. An
individual consent form from every patient was deemed not necessary as
the study was retrospective and the data was kept anonymised.

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  Kajimoto K, Yamamoto T, Amano A. Coronary artery bypass
  revascularization using bilateral internal thoracic arteries in
  diabetic patients: a systematic review and meta-analysis. Ann Thorac
  Surg, 2015;99(3):1097-104.
\item
  Kinoshita T, Asai T, Suzuki T, Kuroyanagi S, Hosoba S, Takashima N et
  al. Off-pump bilateral skeletonized internal thoracic artery grafting
  in elderly patients. Ann Thorac Surg 2012;93:531-6.
\item
  Grau JB, Ferrari G, Mak AWC, Shaw RE, Brizzio ME, Mindich BP et al.
  Propensity matched analysis of bilateral internal mammary artery
  versus single left internal mammary artery grafting at 17-year
  follow-up: validation of a contemporary surgical experience. E J
  Cardiothorac Surg 2012;41(4):770-776.
\item
  Kurlanksy PA, Traad EA, Dorman MJ, Galbut DL, Zucker M , Ebra G.
  Thirty-year follow-up defines survival benefit for second internal
  mammary artery in propensity-matched groups. Ann Thorac Surg
  2010;90:101-8.
\end{enumerate}

\begin{enumerate}
\tightlist
\item
  Lytle BW, Blackstone EH, Sabik JF, Houghtaling P, Loop FD, Cosgrove
  DM. The effect of bilateral internal thoracic artery grafting on
  survival during 20 postoperative years. Ann Thorac Surg
  2004;78:2005-14.
\item
  Taggart DP, Altman DG, Gray AM, Lees B, Nugara F, Yu LM et al. Effects
  of on-pump and off-pump surgery in the Arterial Revascularization
  Trial. Eur J Cardiothorac Surg 2015;47(6):1059-65.
\item
  Taggart DP, Altman DG, Gray AM. Lees B, Nugara F, Yu LM et al.
  Randomized trial to compare bilateral vs. internal mammary coronary
  artery bypass grafting: 1-year results for the Arterial
  Revascularisation Trial (ART). Eur Heart J 2010;31:2470-81.
\item
  Taggart DP, Altman DG, Gray AM. Lees B, Gerry S, Benedetto U et al.
  Randomized trial of bilateral versus single internal-thoracic artery
  grafts. N Engl J Med, 2016;375:2540-2549.
\item
  Taggart DP. Benedetto U, Gerry S, Altman DG, Gray AM, Lees Bet al.
  Bilateral versus single internal-thoracic artery grafts at 10 years. M
  Engl J Med 2019; 380:43-446.
\item
  Benedetto U, Altman DG, Gerry S, Gray A, Lees B, Flather M et al.
  Off-pump versus on-pump coronary artery bypass grafting: Insight from
  the Arterial Revascularisation Trial. J Thorac Cardiovasc Surg
  2018;155:1545-53).
\item
  Benedetto U, Altman DG, Gerry S, Gray A, Lees B, Pawlaczyk P et al.
  Pedicled and skeletonized single and bilateral internal thoracic
  artery grafts and the incidence of sternal wound complications:
  Insights from the Arterial Revascularization Trial. J Thorac Cardiovas
  Surg 2016; 152:270-6.
\item
  Raja SG. Surgical strategies for bilateral internal mammary artery
  grafting. Int J Surg 2015(16);140-145.
\item
  Robinson BM, Paterson HS, Naidoo R, Dhurandhar V, Denniss AR.
  Bilateral internal thoracic artery composite Y grafts: analysis of 464
  angiograms in 296 patients. Ann Thorac Surg 2016;101:974-80.
\item
  Umakanthan J, Jeyakumar P, Umakanthan B, Jeyakumar N, Senthilkumar N,
  Saraswathy MR et al. Barriers to the universal adoption of bilateral
  internal mammary artery grafting. Int J Surg 2015:16;179-182
\item
  LaPar DJ, Crosby IK, Rich JB, Quader MA, Speir AM, Kern JA et al.
  Bilateral internal mammary artery use for coronary artery bypass
  grafting remains underutilized: a propensity-matched multi-institution
  analysis. Ann Thorac Surg 2015;100:8-15.
\item
  Benedetto U, Gaudino M, Caputo M, Tranbaugh RF, Lau C, Di Franco A et
  al. Right internal thoracic artery versus radial artery as the second
  best arterial conduit: Insights from a meta-analysis of
  propensity-matched data on long-term survival. J Thorac Cardiovasc
  Surg, 2016; 152:1083-91.
\item
  Pevni D, Mohr R, Paz Y, Kramer A, Ben-Gal Y, Nesher N et al. Long-term
  outcome of revascularization with composite T-grafts: Is bilateral
  mammary grafting better than single mammary and radial artery
  grafting? J Thorac Cardiovasc Surg 2016;151:1311-1319.
\item
  Benedetto U, Caputo M, Zakkar M, Bryan A, Angelini GA. Are three
  arteries better than two? Impact of using the radial artery in
  addition to bilateral internal thoracic artery grafting on long-term
  survival. J Thorac Cardiovasc Surg, 2016
\item
  Mohammadi S, Dagenais F, Voisine P, Dumont E, Charbonneau E, Marzouk M
  et al. Impact of the radial artery as and additional arterial conduit
  during in-situ bilateral internal mammary artery grafting: a
  propensity score-matched study. Ann Thorac Surg 2016;101:913-8.
\item
  Lamy A, Deverauz PJ, Prabhakaran D, Taggart DP, Hu S, Paolasso E et
  al. Effects of off-pump and on-pump coronary artery bypass grafting at
  1 year. N Engl J Med 2013; 368:1179-1188.
\item
  Shroyer Al, Grover FL, Hattler B, Collins JF, McDonald GO, Kozora E et
  al. On-pump versus off-pump coronary-artery bypass surgery. N Engl J
  med 2009; 361:1824-1837.
\end{enumerate}

\emph{6. TABLES}

Table 1. Preoperative characteristics\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& SIMA & BIMA & P & SIMA matched & BIMA matched & P\tabularnewline
\midrule
\endhead
& n = 681 & n = 342 & & n = 342 & n = 342 &\tabularnewline
Age & 69.4 \selectlanguage{ngerman}± 7.7 (38-85) & 59.4 \selectlanguage{ngerman}± 9.1 (34-85) & 0.001 & 69.5 \selectlanguage{ngerman}± 7.9
(40-87) & 59.4 \selectlanguage{ngerman}± 9.1 (34-85) & 0.001\tabularnewline
Female & 147 (22\%) & 31 (9\%) & 0.001 & 29 (8\%) & 31 (9\%) &
0.89\tabularnewline
Angina CCS II-III & 269 (39\%) & 117 (34\%) & 0.1 & 110 (32\%) & 117
(34\%) & 0.63\tabularnewline
NYHA III-IV & 167 (24\%) & 60 (17\%) & 0.01 & 58 (17\%) & 60 (17\%) &
0.92\tabularnewline
Hypertension & 540 (79\%) & 230 (67\%) & 0.001 & 243 (71\%) & 230 (67\%)
& 0.32\tabularnewline
Diabetes & 216 (32\%) & 73 (21\%) & 0.001 & 76 (22\%) & 73 (21\%) &
0.85\tabularnewline
Hypercholesterolaemia & 613 (90\%) & 301 (88\%) & 0.33 & 310 (91\%) &
301 (88\%) & 0.32\tabularnewline
Family history IHD & 405 (59\%) & 242 (71\%) & 0.001 & 201 (59\%) & 242
(71\%) & 0.001\tabularnewline
Smoking history & 451 (66\%) & 242 (71\%) & 0.14 & 221 (65\%) & 242
(71\%) & 0.10\tabularnewline
Previous MI & 378 (55\%) & 154 (45\%) & 0.005 & 172 (50\%) & 154 (45\%)
& 0.19\tabularnewline
Previous PCI & 58 (8\%) & 38 (11\%) & 0.24 & 34 (10\%) & 38 (11\%) &
0.71\tabularnewline
Previous surgery & 5 (1\%) & 2 (1\%) & 0.72 & 2 (1\%) & 2 (1\%) &
0.99\tabularnewline
Atrial fibrillation & 42 (6\%) & 8 (2\%) & 0.01 & 6 (2\%) & 8 (2\%) &
0.79\tabularnewline
COPD & 116 (17\%) & 34 (10\%) & 0.002 & 32 (9\%) & 34 (10\%) &
0.89\tabularnewline
CVA/TIA & 71 (10\%) & 18 (5\%) & 0.001 & 18 (5\%) & 18 (5\%) &
0.99\tabularnewline
Hemodialysis & 12 (2\%) & 2 (1\%) & 0.13 & 6 (2\%) & 2 (1\%) &
0.29\tabularnewline
Carotid disease & 34 (5\%) & 9 (3\%) & 0.08 & 8 (2\%) & 9 (3\%) &
0.99\tabularnewline
PVD & 133 (19\%) & 35 (10\%) & 0.001 & 38 (11\%) & 35 (10\%) &
0.81\tabularnewline
DVT & 9 (1\%) & 3 (1\%) & 0.53 & 6 (2\%) & 9 (3\%) & 0.62\tabularnewline
Varicose veins & 124 (18\%) & 58 (17\%) & 0.001 & 56 (16\%) & 58 (17\%)
& 0.78\tabularnewline
Obesity & 272 (40\%) & 151(44\%) & 0.07 & 124 (36\%) & 147 (43\%) &
0.24\tabularnewline
BMI & 29.2 \selectlanguage{ngerman}± 4.7 (15-49) & 29.2 \selectlanguage{ngerman}± 4.5 (19-65) & 0.33 & 29.69 \selectlanguage{ngerman}± 4.5
(20-49) & 29.2 \selectlanguage{ngerman}± 5.5 (19-65) & 0.72\tabularnewline
\bottomrule
\end{longtable}

Preoperative characteristics in patients who underwent isolated OPCAB
using single or bilateral internal mammary arteries. Results displayed
for the non-matched and matched populations. BIMA: Bilateral Internal
Mammary Artery; BMI: Body Mass Index; CCS: Angina Canadian
Cardiovascular Society Angina score; COPD: Chronic Obstructive Pulmonary
Disease; CVA: Cerebral vascular accident; DVT: Deep Venous Thrombosis;
IHD: Ischemic Heart Disease; MI: Myocardial Infarct; NYHA: New York
Heart Association Dyspnea Score; PCI: Percutaneous Coronary
Intervention; PVD: Peripheral Vascular Disease; SIMA: Single Internal
Mammary Artery; TIA: Transient Ischemic Attack

Table 2. Extent of coronary disease and timing of surgery\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& SIMA & BIMA & P & SIMA matched & BIMA matched & P\tabularnewline
\midrule
\endhead
& n = 681 & n = 342 & & n = 342 & n = 342 &\tabularnewline
LMS & 219 (32\%) & 127 (37\%) & 0.11 & 108 (31\%) & 127 (37\%) &
0.15\tabularnewline
2 VD & 114 (17\%) & 69 (20\%) & 0.18 & 63 (18\%) & 69 (20\%) &
0.66\tabularnewline
3 VD & 567 (83\%) & 273 (80\%) & 0.18 & 279 (81\%) & 273 (80\%) &
0.66\tabularnewline
Good LV & 384 (56\%) & 240 (71\%) & 0.001 & 206 (60\%) & 240 (70\%) &
0.008\tabularnewline
Fair LV & 258 (38\%) & 94 (27\%) & 0.001 & 119 (35\%) & 94 (27\%) &
0.05\tabularnewline
Poor LV & 39 (6\%) & 8 (2\%) & 0.01 & 17 (5\%) & 8 (2\%) &
0.10\tabularnewline
In-house & 319 (47\%) & 141 (41\%) & 0.05 & 153 (45\%) & 141 (41\%) &
0.44\tabularnewline
Emergency & 23 (3\%) & 6 (2\%) & 0.05 & 3 (1\%) & 3 (1\%) &
0.99\tabularnewline
Preoperative IABP & 20 (3\%) & 3 (1\%) & 0.04 & 3 (1\%) & 3 (1\%) &
0.95\tabularnewline
Logistic EuroScore & 6.1 \selectlanguage{ngerman}± 8.0 (1 -- 61) & 4.7 \selectlanguage{ngerman}± 8.5 (1 -- 60) & 0.43 &
5.1 \selectlanguage{ngerman}± 7.2 (1 - 53) & 4.7 \selectlanguage{ngerman}± 8.5 (1- 60) & 0.64\tabularnewline
\bottomrule
\end{longtable}

Extent of coronary disease, preoperative ventricular function and timing
of the surgery in patients who underwent isolated OPCAB using single or
bilateral internal mammary arteries (BIMA). Results displayed for the
non-matched and matched populations. BIMA: Bilateral Internal Mammary
Artery; IABP: Intra-Aortic Balloon Pump; LMS: Left Main Stem, LV: Left
Ventricle; SIMA: Single Internal Mammary Artery; VD: Vessels Disease.

Table 3. Revascularisation strategy\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& SIMA & BIMA & P & SIMA matched & BIMA matched & P\tabularnewline
\midrule
\endhead
& n = 681 & n = 342 & & n = 342 & n = 342 &\tabularnewline
Distal anastomosis & 3.7 \selectlanguage{ngerman}± 0.8 (1-5) & 3.7 \selectlanguage{ngerman}± 0.8 (2-6) & 0.11 & 3.7 \selectlanguage{ngerman}±
0.8 (1-5) & 3.6 \selectlanguage{ngerman}± 0.9 (2-6) & 0.06\tabularnewline
Arterial grafts & 1.1 \selectlanguage{ngerman}± 0.3 (1-2) & 2.8 \selectlanguage{ngerman}± 0.6 (2-5) & 0.001 & 1.2 \selectlanguage{ngerman}± 0.4
(1-2) & 2.8 \selectlanguage{ngerman}± 0.7 (2-5) & 0.001\tabularnewline
Venous grafts & 2.5 \selectlanguage{ngerman}± 0.8 (0-4) & 0.8 \selectlanguage{ngerman}± 0.8 (0-3) & 0.001 & 2.5 \selectlanguage{ngerman}± 0.8
(0-4) & 0.8 \selectlanguage{ngerman}± 0.8 (0-3) & 0.001\tabularnewline
SIMA & 681 (100\%) & 0 & 0.001 & 262 (100\%) & 0 & 0.001\tabularnewline
2nd arterial graft (BIMA) & 0 & 342 (100\%) & 0.001 & 0 & 342 (100\%) &
0.001\tabularnewline
3rd arterial graft (BIMA/RADIAL) & 0 & 67 (20\%) & 0.001 & 0 & 67 (20\%)
& 0.001\tabularnewline
Total arterial & 0 & 109 (42\%) & 0.001 & 0 & 148 (42\%) &
0.001\tabularnewline
Incomplete revascularisation & 3 (1\%) & 0 & 0.08 & 1 (0.3\%) & 0 &
0.99\tabularnewline
\bottomrule
\end{longtable}

Revascularization strategy in patients who underwent isolated OPCAB
using single or bilateral internal mammary arteries. Results displayed
for the non-matched and matched populations. BIMA: Bilateral Internal
Mammary Artery; SIMA: Single Internal Mammary Artery

Table 4. Postoperative complications\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& SIMA & BIMA & P & SIMA matched & BIMA matched & P\tabularnewline
\midrule
\endhead
& n = 681 & n = 342 & & n = 342 & n = 342 &\tabularnewline
Reoperation for bleeding & 17 (2\%) & 3 (1\%) & 0.08 & 9 (3\%) & 3 (1\%)
& 0.14\tabularnewline
Reoperation for DSWI & 8 (1\%) & 3 (1\%) & 0.67 & 4 (1\%) & 3 (1\%) &
0.99\tabularnewline
Postoperative CVA/TIA & 9 (1\%) & 0 & 0.4 & 5 (1\%) & 0 &
0.07\tabularnewline
Postop hemofiltration & 33 (5\%) & 12 (3\%) & 0.3 & 9 (3\%) & 8 (2\%) &
0.99\tabularnewline
Deep sternal wound infection & 17 (2\%) & 8 (2\%) & 0.9 & 9 (3\%) & 8
(2\%) & 0.76\tabularnewline
Atrial fibrillation & 157 (23\%) & 51 (15\%) & 0.01 & 78 (23\%) & 51
(15\%) & 0.01\tabularnewline
Pneumonia/ARDS & 15 (2\%) & 4 (1\%) & 0.25 & 8 (2\%) & 4 (1\%) &
0.38\tabularnewline
Prolonged ventilation/Tracheostomy & 8 (1\%) & 2 (1\%) & 0.37 & 5 (1\%)
& 2 (1\%) & 0.45\tabularnewline
Chest infection & 62 (9\%) & 22 (6\%) & 0.14 & 31 (9\%) & 22 (6\%) &
0.25\tabularnewline
Sepsis & 4 (1\%) & 2 1\%) & 0.99 & 3 (1\%) & 2 (1\%) &
0.99\tabularnewline
Leg wound infection & 28 (4\%) & 2 (1\%) & 0.9 & 14 (4\%) & 2 (1\%) &
0.005\tabularnewline
Pacemaker/ICD insertion & 6 (1\%) & 2 (1\%) & 0.91 & 3 (1\%) & 1 (0.3\%)
& 0.27\tabularnewline
GI complications & 17 (2\%) & 5 (2\%) & 0.02 & 6 (2\%) & 5 (1\%) &
0.99\tabularnewline
Hospital mortality & 16 (2\%) & 2 (1\%) & 0.05 & 7 (2\%) & 2 (1\%) &
0.18\tabularnewline
\bottomrule
\end{longtable}

Postoperative complications in patients who underwent isolated OPCAB
using single or bilateral internal mammary arteries. Results displayed
for the non-matched and matched populations. ARDS: Acute Respiratory
Distress Syndrome; BIMA: Bilateral Internal Mammary Artery; CVA:
Cerebrovascular Accident; DSWI: Deep Sternal Wound Infection; GI:
Gastrointestinal; ICD: Implantable Cardioverter Defibrillator; SIMA:
Single Internal Mammary Artery; TIA: Transient Ischemic Attack

Table 5. Long-term survival\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& SIMA & BIMA & P & SIMA matched & BIMA matched & P\tabularnewline
\midrule
\endhead
& n = 681 & n = 342 & & n = 342 & n = 342 &\tabularnewline
Late mortality & 162 (24\%) & 34 (10\%) & 0.001 & 72 (21\%) & 34 (10\%)
& 0.001\tabularnewline
One-year mortality & 22 (3\%) & 3 (1\%) & 0.06 & 8 (2\%) & 3 (1\%) &
0.22\tabularnewline
One-year survival & 639 (97\%) & 326 (99\%) & 0.06 & 320 (98\%) & 326
(99\%) & 0.22\tabularnewline
Five-year mortality & 82 (17\%) & 14 (5\%) & 0.001 & 40 (16\%) & 14
(5\%) & 0.001\tabularnewline
Five-year survival & 403 (83\%) & 256 (95\%) & 0.001 & 210 (84\%) & 256
(95\%) & 0.001\tabularnewline
\bottomrule
\end{longtable}

Long-term survival in patients who underwent isolated OPCAB using single
or bilateral internal mammary arteries. Results displayed for the
non-matched and matched populations.

BIMA: Bilateral Internal Mammary Artery; SIMA: Single Internal Mammary
Artery

Table 6. Follow-up events\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& SIMA & BIMA & P & SIMA matched & BIMA matched & P\tabularnewline
\midrule
\endhead
& n = 519 & n = 306 & & n = 263 & n = 306 &\tabularnewline
Angina CCS II-III & 37 (7\%) & 29 (9\%) & 0.06 & 15 (6\%) & 29 (9\%) &
0.06\tabularnewline
NYHA III-IV & 28 (5\%) & 9 (3\%) & 0.23 & 13 (5\%) & 9 (3\%) &
0.45\tabularnewline
CVA/TIA & 16 (3\%) & 8 (3\%) & 0.34 & 9 (3\%) & 8 (3\%) &
0.92\tabularnewline
Myocardial infarct & 13 (2\%) & 10 (3\%) & 0.23 & 6 (2\%) & 11 (4\%) &
0.51\tabularnewline
Re-angiogram & 35 (7\%) & 26 (9\%) & 0.13 & 13 (5\%) & 26 (9\%) &
0.07\tabularnewline
Patent grafts & 14 (2\%) & 7 (2\%) & 0.3 & 6 (2\%) & 8 (3\%) &
0.13\tabularnewline
PCI & 11 (2\%) & 10 (3\%) & 0.13 & 6 (2\%) & 11 (4\%) &
0.4\tabularnewline
Missing & 1 (0.1\%) & 32 (10\%) & & 0 & 32 (10\%) &\tabularnewline
\bottomrule
\end{longtable}

Follow-up events in patients who underwent isolated OPCAB using single
or bilateral internal mammary arteries. Results displayed for the
non-matched and matched populations.

BIMA: Bilateral Internal Mammary Artery; CCS: Canadian Cardiovascular
Society Angina score; CVA: Cerebrovascular Accident; NHYA: New York
Heart Association Dyspnea score; PCI: Percutaneous Coronary
Intervention; SIMA: Single Internal Mammary Artery; TIA: Transient
Ischemic Attack

\textbf{8. FIGURE LEGENDS}

Figure 1: Kaplan Meier survival curve in patients who underwent isolated
OPCAB using single (SIMA) or bilateral internal mammary arteries (BIMA).
Results displayed for the matched populations. The number of patients at
risk at each point is displayed in the table.\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
Years & 2 & 4 & 6 & 8 & 10\tabularnewline
\midrule
\endhead
BIMA & 313 & 278 & 235 & 169 & 91\tabularnewline
SIMA & 303 & 252 & 172 & 107 & 51\tabularnewline
\bottomrule
\end{longtable}

Figure 2: Kaplan Meier survival curve in patients who underwent isolated
OPCAB using single (SIMA) or bilateral internal mammary arteries (BIMA).
Results displayed for the non-matched population. The number of patients
at risk at each point is displayed in the table.\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
Years & 2 & 4 & 6 & 8 & 10\tabularnewline
\midrule
\endhead
BIMA & 304 & 263 & 217 & 155 & 72\tabularnewline
SIMA & 574 & 443 & 311 & 180 & 80\tabularnewline
\bottomrule
\end{longtable}

\selectlanguage{english}
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