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Long-term outcomes of patients receiving right internal thoracic artery or radial artery as a second arterial conduit. A propensity score matching study

  • Sleiman Sebastian Aboul-Hassan
    Correspondence
    Corresponding author at: Department of Cardiac Surgery, Medinet Heart Center Ltd., Chalubinskiego 7 street, 67-100 Nowa Sol, Poland.
    Affiliations
    Department of Cardiac Surgery, MEDINET Heart Center Ltd, Nowa Sol, Poland

    Department of Cardiac Surgery and Interventional Cardiology, Faculty of Medicine and Medical Sciences, University of Zielona Gora, Zielona Gora, Poland
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  • Tomasz Stankowski
    Affiliations
    Department of Cardiac Surgery, Sana-Heart Center Cottbus, Cottbus, Germany
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  • Jakub Marczak
    Affiliations
    Department of Thoracic Aortic Aneurysm Service, Liverpool Heart and Chest NHS Foundation Trust, Liverpool, UK
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  • Bartlomiej Perek
    Affiliations
    Department of Cardiac Surgery and Transplantology, Chair of Cardio-Thoracic Surgery, Poznan University of Medical Sciences, Poznan, Poland
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  • Anna Olasinska-Wisniewska
    Affiliations
    Department of Cardiac Surgery and Transplantology, Chair of Cardio-Thoracic Surgery, Poznan University of Medical Sciences, Poznan, Poland
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  • Tomasz Urbanowicz
    Affiliations
    Department of Cardiac Surgery and Transplantology, Chair of Cardio-Thoracic Surgery, Poznan University of Medical Sciences, Poznan, Poland
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  • Marek Jemielity
    Affiliations
    Department of Cardiac Surgery and Transplantology, Chair of Cardio-Thoracic Surgery, Poznan University of Medical Sciences, Poznan, Poland
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  • Lukasz Moskal
    Affiliations
    Department of Cardiac Surgery, MEDINET Heart Center Ltd, Wroclaw, Poland
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  • Weronika Majchrowicz
    Affiliations
    Department of Cardiac Surgery, MEDINET Heart Center Ltd, Nowa Sol, Poland

    Department of Cardiac Surgery and Interventional Cardiology, Faculty of Medicine and Medical Sciences, University of Zielona Gora, Zielona Gora, Poland
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  • Michel Pompeu Sá
    Affiliations
    Department of Cardiac Surgery Research, Lankenau Institute for Medical Research, Main Line Health, Wynnewood, PA, USA

    Department of Cardiothoracic Surgery, Lankenau Heart Institute, Main Line Health, Wynnewood, PA, USA
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  • Ahmed K. Awad
    Affiliations
    Department of Cardiac Surgery Research, Lankenau Institute for Medical Research, Main Line Health, Wynnewood, PA, USA

    Faculty of Medicine, Ain-Shams University, Cairo, Egypt
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  • Gianluca Torregrossa
    Affiliations
    Department of Cardiac Surgery Research, Lankenau Institute for Medical Research, Main Line Health, Wynnewood, PA, USA

    Department of Cardiothoracic Surgery, Lankenau Heart Institute, Main Line Health, Wynnewood, PA, USA
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  • Basel Ramlawi
    Affiliations
    Department of Cardiac Surgery Research, Lankenau Institute for Medical Research, Main Line Health, Wynnewood, PA, USA

    Department of Cardiothoracic Surgery, Lankenau Heart Institute, Main Line Health, Wynnewood, PA, USA
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  • Romuald Cichon
    Affiliations
    Department of Cardiac Surgery, MEDINET Heart Center Ltd, Nowa Sol, Poland

    Department of Cardiac Surgery and Interventional Cardiology, Faculty of Medicine and Medical Sciences, University of Zielona Gora, Zielona Gora, Poland

    Department of Cardiac Surgery, MEDINET Heart Center Ltd, Wroclaw, Poland
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Open AccessPublished:October 31, 2022DOI:https://doi.org/10.1016/j.ijcard.2022.10.156

      Highlights

      • The use of RITA or RA is associated with comparable early outcomes including mortality, stroke, MI and wound infection.
      • The use of RITA as well as RA as a second graft is associated with comparable long-term survival and freedom from MACCE.
      • No difference in long-term MACCE was observed between RITA and RA with respect to age, sex, diabetes, obesity or reduced EF.
      • RITA and RA had comparable outcomes in terms of MACCE when grafted either to the left or the right coronary system.

      Abstract

      Objective

      This study aimed to compare the long-term outcomes in propensity matched patients receiving right internal thoracic artery(RITA) or radial artery(RA) as second arterial conduit during coronary artery bypass grafting(CABG) with internal thoracic artery to the left anterior descending artery(LAD).

      Methods

      In this retrospective study, propensity score matching was performed including 1198 patients from 3 centers resulting in 389-pairs who received either RITA or RA.

      Results

      In the matched cohort, median follow-up time was 7.53 years(interquartile range, 4.35–11.81). Survival probabilities at 5, 10 and 15-years were 93.8% versus 94.5%, 81.2% versus 76.2% and 63.2% vs 62.5% in the RITA and RA groups, respectively(HR: 1.11; 95%CI;0.80–1.53; P = 0.533) Freedom from MACCE in the matched cohort at 5, 10 and 15-years were 92.0% versus 93.7%, 75.0% versus 73.8%, 72.2% and 46.9% vs 47.2% in the RITA and RA groups, respectively(HR: 0.96; 95%CI;0.74–1.26; P = 0.774). Subgroup analyses of the matched cohort showed comparable long-term outcomes in terms of MACCE at follow-up in patients with age older than 65-years, obese patients, diabetics, female patients and with impaired EF. As for target vessel revascularization, RITA and RA had comparable outcomes in terms of MACCE when the conduit was used to graft either the left coronary system or the right coronary system.

      Conclusions

      The use of RITA or RA as second arterial conduit during CABG with internal thoracic artery to the LAD is safe and associated with comparable long-term clinical outcomes. The choice of optimal second arterial conduit should be guided mainly by patients' characteristics and surgeons' preferences.

      Keywords

      1. Introduction

      Coronary artery bypass grafting (CABG) is considered to be the treatment of choice for multivessel coronary artery disease and left main disease [
      • Neumann F.J.
      • Sousa-Uva M.
      • Ahlsson A.
      • Alfonso F.
      • Banning A.P.
      • Benedetto U.
      • et al.
      2018 ESC/EACTS Guidelines on myocardial revascularization.
      ,
      • Sá M.P.
      • Soares A.M.
      • Lustosa P.C.
      • Martins W.N.
      • Browne F.
      • Ferraz P.E.
      • Vasconcelos F.P.
      • Lima R.C.
      Meta-analysis of 5,674 patients treated with percutaneous coronary intervention and drug-eluting stents or coronary artery bypass graft surgery for unprotected left main coronary artery stenosis.
      ]. Revascularization of the left anterior descending artery (LAD) using internal thoracic artery is the gold standard. On the other hand, several studies showed that the addition of a second arterial graft improved long-term survival and reduced the incidence of major adverse cardiac and cerebral events (MACCE) when compared with using the saphenous vein [
      • Chikwe J.
      • Sun E.
      • Hannan E.L.
      • Itagaki S.
      • Lee T.
      • Adams D.H.
      • et al.
      Outcomes of second arterial conduits in patients undergoing multivessel coronary artery bypass graft surgery.
      ,
      • Locker C.
      • Schaff H.V.
      • Dearani J.A.
      • Joyce L.D.
      • Park S.J.
      • Burkhart H.M.
      • et al.
      Multiple arterial grafts improve late survival of patients undergoing coronary artery bypass graft surgery: analysis of 8622 patients with multivessel disease.
      ,
      • Aboul-Hassan S.S.
      • Marczak J.
      • Stankowski T.
      • Moskal L.
      • Stanislawski R.
      • Perek B.
      • et al.
      Impact of second arterial conduit on outcomes following coronary bypass grafting.
      ,
      • Schwann T.A.
      • Hashim S.W.
      • Badour S.
      • Obeid M.
      • Engoren M.
      • Tranbaugh R.F.
      • et al.
      Equipoise between radial artery and right internal thoracic artery as the second arterial conduit in left internal thoracic artery-based coronary artery bypass graft surgery: a multi-institutional study.
      ]. However, it is still unclear whether radial artery (RA) or right internal thoracic artery (RITA) is the better second conduit to supplement left internal thoracic artery (LITA).
      The long-term results of the RAPCO trial showed that the RA is associated with reduced incidence of graft failure and mortality when compared to free RITA graft [
      • Buxton B.F.
      • Hayward P.A.
      • Raman J.
      • Moten S.C.
      • Rosalion A.
      • Gordon I.
      • et al.
      Long-term results of the RAPCO trials.
      ]. In contrary, Benedetto et al. [
      • Benedetto U.
      • Caputo M.
      • Gaudino M.
      • Marsico R.
      • Rajakaruna C.
      • Bryan A.
      • et al.
      Right internal thoracic artery or radial artery? A propensity-matched comparison on the second-best arterial conduit.
      ] and Ruttmann et al. [
      • Ruttmann E.
      • Fischler N.
      • Sakic A.
      • Chevtchik O.
      • Alber H.
      • Schistek R.
      • et al.
      Second internal thoracic artery versus radial artery in coronary artery bypass grafting: a long-term, propensity score-matched follow-up study.
      ] showed superior outcomes of RITA graft compared to RA as second best arterial graft. Therefore, till this date, the debate on which of the second best arterial conduit continues. The aim of this study is to compare the long-term outcomes in propensity matched patients receiving RITA or RA as second arterial conduit during CABG with internal thoracic artery to the LAD.

      2. Methods

      2.1 Study design

      This observational, retrospective study was designed with reference to STROBE guidelines (Strengthening The Reporting of Observational Studies in Epidemiology) [
      • Vandenbroucke J.P.
      • von Elm E.
      • Altman D.G.
      • Gotzsche P.C.
      • Mulrow C.D.
      • Pocock S.J.
      • et al.
      Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration.
      ]. Between January 2006 and December 2020, 1390 patients underwent isolated CABG using multiple arterial grafts at three cardiac surgery centers (Medinet Heart Center Ltd. in Nowa Sol and Wroclaw and Poznan University of Medical Sciences, Poland). We retrospectively analyzed prospectively collected data from the surgical database in those centers. The data was collected and reported in accordance with Polish National Registry of Cardiac Surgery Procedures database which is mandatory for every cardiac surgery department in Poland. The database captures detailed information on preoperative, intraoperative, and hospital postoperative variables for all patients undergoing any cardiac surgery procedure.
      Patients included in the final analysis met the following criteria: first-time isolated CABG with multivessel disease requiring at least two coronary grafts; one of the ITA's used in situ to graft LAD territory and additional second ITA in-situ or as composite graft for non-LAD target (RITA group) or the use of RA as second graft for the non-LAD target (RA group). Patients with additional SVG were also included. ITA's were harvested as pedicled or skeletonized graft, whereas RA was harvested as pedicled graft. RITA was used as an in-situ graft or as a composite graft proximally connected to LITA. RITA or RA were used in cases where target stenosis was >70% in the left coronary system or in isolated left main disease (>50%) as well as in cases where target stenosis was >80% in the right coronary system. RA was used as a free graft directly connected to the ascending aorta or as composite graft proximally connected to the LITA. Patients with three arterial conduits or when any ITA was used as free graft connected to the ascending aorta or LAD not grafted with ITA were excluded from the study. The arterial graft targets are summarized in Table S1.
      Overall, 1198 patients met the inclusion criteria and were divided into two groups: RITA group (n = 809) and RA group (n = 389). Fig. 1 represents patients flow chart diagram. The use of multiple arterial grafts (MAG) in the overall population was 10.8%. However, when stratified by each center, the rate of MAG in Medinet Heart Center Nowa Sol was 28.6%, 2.7% in Medinet Heart Center Wroclaw and 14.6% in Poznan University of Medical Sciences. Postoperative medication at discharge is summarized in table S2. The study was approved by the Institutional Review Board at Medinet Heart Center in Nowa Sol and Wroclaw and in Poznan University of Medical Sciences. Individual consent for anonymous data analysis was waived by the Ethics Committee.
      Fig. 1
      Fig. 1Strengthening the reporting of observational studies in epidemiology (STROBE) flow diagram detailing selection of patients within each group. The diagram presents included and excluded patients as well as number of patients before and after propensity score matching. CABG: Coronary artery bypass grafting; RITA: Right internal thoracic artery; RA: Radial artery; ITA: Internal thoracic artery; LAD: Left anterior descending artery; SVG: Saphenous vein graft.

      2.2 Study endpoints and definitions

      Short-term outcomes included: 30-day mortality, in-hospital myocardial infarction (MI), in-hospital stroke, reoperation for bleeding, postoperative renal replacement therapy (RRT), postoperative intra -aortic balloon pump (IABP) and deep sternal wound infection (DSWI). MI was defined according to the fourth international definition of MI [
      • Thygesen K.
      • Alpert J.S.
      • Jaffe A.S.
      • Chaitman B.R.
      • Bax J.J.
      • Morrow D.A.
      • et al.
      Fourth universal definition of myocardial infarction (2018).
      ]. Stroke was defined as the development of a new permanent neurologic deficit as confirmed by stroke team member assessment of the patient and computed tomography of the central nervous system, magnetic resonance imaging, or at autopsy examination. DSWI was defined according to criteria established by the Center for Disease Control and Prevention [
      • Mangram A.J.
      • Horan T.C.
      • Pearson M.L.
      • Silver L.C.
      • Jarvis W.R.
      • Guideline for Prevention of Surgical Site Infection
      Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee.
      ].
      The long-term outcomes were all-cause mortality and incidence of MACCE (composite endpoints including mortality, myocardial infarction, and stroke). All-cause mortality was assessed which is considered as an objective and unbiased endpoint for comparative studies [
      • Lauer M.S.
      • Blackstone E.H.
      • Young J.B.
      • Topol E.J.
      Cause of death in clinical research: time for a reassessment?.
      ]. Information about MACCE at follow-up was retrieved from the National Health Care registry of the Ministry of Health of the Republic of Poland which stores and analyzes all health-related data. Data regarding postoperative outcomes were available for all patients in the study.

      2.3 Statistical analysis

      Continuous variables were expressed as means ± SD, while categorical variables as numbers and percentages. For continuous data Student's t-test was used for in between groups comparisons, while categorical variables were compared with Pearson-χ2-test.
      In order to reduce the impact of confounders inherent to any observational studies, a propensity score (PS) matching was applied. Propensity scores were generated from a multivariable logistic regression model based on baseline characteristics in addition to operative variables (Off-pump coronary artery bypass -OPCAB, number of grafts) and included centers (Table-1). Patients were then matched in to 1:1 fashion using nearest neighbor within caliper matching method without replacement with a caliper width of 0.2 standard deviation of the logit of the PS. The balance of the covariates was tested using standardized mean difference (SMD). Statistical guidelines suggest a meaningful covariate balance of the variables used to generate the PS between the two groups to be between SMD ≤ 0.1. Matched data were analyzed using procedures for matched analyses. Continuous data were analyzed using paired student t-test, while McNemar's test was used for categorical outcomes [
      • Benedetto U.
      • Head S.J.
      • Angelini G.D.
      • Blackstone E.H.
      Statistical pri-mer: propensity score matching and its alternatives.
      ,
      • Austin P.C.
      Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies.
      ,
      • Austin P.C.
      Statistical criteria for selecting the optimal number of untreated subjects matched to each treated subject when using many-to-one matching on the propensity score.
      ,
      • Austin P.C.
      A tutorial and case study in propensity score analysis: an application to estimate the effect of in-hospital smoking cessation counseling on mortality.
      ,
      • Collins G.S.
      • Le Manach Y.
      Comparing treatment effects between propensity scores and randomized controlled trials: improving conduct and reporting.
      ].
      Survival and freedom from MACCE were estimated using the Kaplan-Meier method. Stratified Log-rank test was used to compare the data. A Cox proportional hazard regression was conducted to evaluate hazard ratio of RITA vs RA. The hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) were reported. PS matched subgroup analyses on late MACCE were stratified according to age > 65 years, female, obesity (BMI ≥30 kg/m2), diabetes, impaired ejection fraction (EF) ≤40% and target vessel revascularization (Left coronary system or right coronary system). The results are presented as HRs and corresponding 95% CI.
      All the statistical analyses were carried out in R (version 4.2.0) (RStudio Team (2020). (RStudio: Integrated Development for R. RStudio, PBC, Boston, MA) (http://www.rstudio.com). Matching was performed using ‘MatchIt’ and ‘optmatch’ packages. P < 0.05 was considered statistically significant in a two-tailed test.

      3. Results

      The study population included a total of 1198 patients, of whom 809 patients received bilateral internal thoracic artery grafts (BITA) with (n = 338) or without (n = 471) additional SV grafts and 389 patients received the LITA+RA with (n = 86) or without (n = 303) additional SV grafts. The patients' baseline characteristics before and after PS matching is demonstrated in Table 1. In the unmatched analysis, when compared to those in RITA group, patients in the RA group tended to have higher burden of co-morbidities, being more likely to be older, female and to have higher BMI, NYHA III-IV score, diabetes, hyperlipidemia and left main disease when compared to patients in the RITA group. PS matching selected 389 pairs and both groups were comparable for all baseline characteristics and well balanced (SMD < 0.1) (Table 1).
      Table 1Baseline and operative characteristics.
      Baseline CharacteristicsBefore matchingAfter matching
      RITA

      (n = 809)
      RA

      (n = 389)
      pSMDRITA

      (n = 389)
      RA

      (n = 389)
      pSMD
      Age (Years)58.7 ± 8.359.8 ± 9.20.0340.12859.8 ± 8.159.8 ± 9.20.99<0.001
       Age > 65169 (20.9)101 (25.9)0.0597 (24.9)101 (25.9)0.74
      Female121 (15.0)81 (20.8)0.0140.15479 (20.3)81 (20.8)0.920.013
      BMI (kg/m2)28.1 ± 2.828.6 ± 4.80.0010.20128.1 ± 2.628.7 ± 4.10.610.042
       BMI ≥30225 (27.8)137 (35.2)0.009112 (28.7)136 (34.9)0.06
      NYHA III-IV79 (9.8)55 (14.1)0.0310.13552 (13.4)55 (14.1)0.830.022
      History of MI445 (55.0)212 (54.5)0.910.01212 (54.5)212 (54.5)>0.99<0.001
      Previous PCI217 (26.8)99 (25.4)0.660.03199 (25.4)99 (25.4)>0.99<0.001
      Smoker200 (24.7)86 (22.1)0.350.06276 (19.5)86 (22.1)0.420.063
      Diabetes174 (21.5)136 (35.0)<0.0010.302127 (32.6)136 (35.0)0.540.049
       Insulin88 (10.9)71 (18.3)0.00166 (17.0)71 (18.3)0.70
      Hypertension690 (85.3)327 (84.1)0.630.034323 (83.0)327 (84.1)0.770.028
      Hyperlipidemia354 (43.8)211 (54.2)0.0010.211199 (51.2)211 (54.2)0.430.062
      Creatinine level (mg/dl)0.98 ± 0.410.98 ± 0.270.830.0131.00 ± 0.510.98 ± 0.270.440.054
      eGFR (mL/min/1.73m2)83.5 ± 21.282.0 ± 23.00.250.0781.6 ± 22.182.0 ± 23.00.800.018
      PVD75 (9.3)33 (8.5)0.730.02837 (9.5)33 (8.5)0.700.036
      History of CAEs13 (1.6)7 (1.8)0.990.0157 (1.8)7 (1.8)>0.99<0.001
      CLD37 (4.6)19 (4.9)0.920.01516 (4.1)19 (4.9)0.720.037
      LM378 (46.7)135 (34.7)<0.0010.247137 (35.2)135 (34.7)0.940.011
      EF (%)53.8 ± 8.952.8 ± 8.70.080.10853.3 ± 9.052.8 ± 8.70.470.051
       EF ≤40%90 (11.1)49 (12.6)0.5149 (12.6)49 (12.6)>0.99
      Non-elective surgery340 (42.0)125 (32.1)0.0010.206131 (33.7)125 (32.1)0.700.033
      Centers:<0.0010.3420.520.081
       NS469 (58.0)212 (54.5)202 (51.9)212 (54.5)
       PZN176 (21.8)134 (34.4)134 (34.4)134 (34.4)
       WRO164 (20.3)43 (11.1)53 (13.6)43 (11.1)
      Operative Characteristics
      OPCAB437 (54.0)194 (49.9)0.190.083190 (48.8)194 (49.9)0.830.021
      Number of grafts2.5 ± 0.62.3 ± 0.5<0.0010.2852.3 ± 0.52.3 ± 0.5>0.99<0.001
      Data are expressed as mean ± SD or n(%), unless otherwise indicated.
      RITA = Right internal thoracic artery; RA = Radial artery; SMD = Standardized mean difference; BMI=Body mass index; NYHA = New York Heart Association; MI = Myocardial infarction; PCI=Percutaneous coronary intervention; eGFR = Estimated glomerular filtration rate; PVD = Peripheral vascular disease; CAEs = Cerebral adverse events; CLD=Chronic lung disease; LM = Left main disease; EF = Ejection fraction; OPCAB=Off-pump coronary artery bypass grafting; NS = Medinet Heart Center in Nowa Sol; PZN=Poznan Medical University; Wro = Medinet Heart Center in Wroclaw.

      3.1 Short-term outcomes

      Short-term outcomes in the unmatched and matched cohorts are summarized in Table 2. The two groups were comparable in terms of 30-day mortality, in-hospital stroke, in-hospital MI, need of postoperative RRT, IABP, incidence of DSWI and reoperation due to bleeding.
      Table 2Postoperative outcomes.
      Before matchingAfter matching
      RITA

      (n = 809)
      RA

      (n = 389)
      PaRITA

      (n = 389)
      RA

      (n = 389)
      Pb
      30-day Mortality3 (0.37)2 (0.5)>0.993 (0.8)2 (0.5)>0.99
      In-hospital MI25 (3.1)6 (1.5)0.1610 (2.6)6 (1.5)0.44
      In-hospital Stroke7 (0.9)2 (0.5)0.764 (1.0)2 (0.5)0.68
      DSWI27 (3.3)7 (1.8)0.1813 (3.3)7 (1.8)0.25
      Post-operative RRT8 (1.0)4 (1.0)>0.996 (1.5)4 (1.0)0.75
      Post-operative IABP9 (1.1)1 (0.3)0.236 (1.5)1 (0.3)0.12
      Reoperation due to bleeding36 (4.4)20 (5.1)0.721 (5.4)20 (5.1)>0.99
      Data are expressed as n(%)
      a-Chi-square test; b-McNemar test.
      RITA = Right internal thoracic artery; RA = Radial Artery; MI = Myocardial infarction; DSWI=Deep sternal wound infection; RRT = Renal replacement therapy; IABP = Intra-aortic balloon pump.

      3.2 Long-term outcomes

      In the matched cohort, median follow-up time was 7.53 years (interquartile range, 4.35–11.81). Survival probabilities at 5, 10 and 15 years were 93.8% versus 94.5%, 81.2% versus 76.2% and 63.2% vs 62.5% in the RITA and RA groups, respectively (Stratified log-rank P = 0.53) (Fig. 2A ).
      Fig. 2
      Fig. 2A- Kaplan-Meier survival curve probabilities in the propensity matched population in the right internal thoracic artery (RITA) and the radial artery (RA) groups. B-Freedom from Major Adverse Cardiac and Cerebral events (MACCE) in the propensity matched population in the right internal thoracic artery (RITA) and the radial artery (RA) groups.
      Freedom from MACCE in the matched cohort at 5, 10 and 15 years were 92.0% versus 93.7%, 75.0% versus 73.8% and 46.9% vs 47.2% in the RITA and RA groups, respectively (Stratified log-rank P = 0.77) (Fig. 2B). RA and RITA had comparable long-term outcomes in terms of mortality (HR: 1.11; 95%CI; 0.80–1.53; P = 0.533) as well as MACCE (HR:0.96; 95%CI; 0.74–1.26; P = 0.774).

      3.3 Subgroup analyses on late MACCE

      Subgroup analyses of the matched cohort showed comparable long-term outcomes in terms of MACCE at follow-up in patients with age older than 65 years (HR:1.04; 95%CI; 0.79–1.36; P = 0.77), obese patients (HR:0.84; 95%CI; 0.56–1.36; P = 0.48), diabetics (HR:0.88; 95%CI; 0.56–1.40; P = 0.61), female patients (HR:1.07; 95%CI; 0.61–1.90; P = 0.79) and with impaired EF (HR:0.86; 95%CI; 0.47–1.59; P = 0.64). As for target vessel revascularization, RITA and RA had comparable outcomes in terms of MACCE when the conduit was used to graft either the left coronary system (HR:0.98; 95%CI; 0.73–1.32; P = 0.93) or the right coronary system (HR:1.37; 95%CI; 0.48–3.91; P = 0.55) (Table 3).
      Table 3HR for MACCE in PS matched subgroups.
      Risk factorPatients (n)HR (95% CI)P
      Age > 65 y198
       RITA971.04 (0.79–1.36)0.77
       RA101Reference
      Female160
       RITA791.07 (0.61–1.90)0.79
       RA81Reference
      BMI ≥ 30 kg/m2248
       RITA1120.84 (0.51–1.36)0.48
       RA136Reference
      Diabetes263
       RITA1270.88 (0.56–1.40)0.61
       RA136Reference
      EF ≤40%99
       RITA500.86 (0.47–1.59)0.64
       RA49Reference
      LCS607
       RITA3720.98 (0.73–1.32)0.93
       RA235Reference
      RCS171
       RITA171.37 (0.48–3.91)0.55
       RA154Reference
      HR = Hazard ratio; CI = confidence interval; RITA = Right internal thoracic artery; RA = Radial artery; BMI = Body mass index; EF = Ejection fraction; LCS = Left coronary system; RCS: Right coronary system.

      4. Discussion

      The present multicenter PS matched study showed that the use of RITA as well as RA as a second arterial graft supplementing in-situ ITA to LAD in patients following CABG had comparable long-term survival as well as comparable freedom from MACCE at follow-up. Subgroup analyses showed no difference in long-term MACCE in diabetic patients as well as in obese patients, female patients and patients older than 65 years old or with reduced EF. As for target vessel revascularization, RITA and RA had comparable outcomes in terms of MACCE when the conduit was used to graft either the left coronary system or the right coronary system. RITA and RA had comparable short-term outcomes with respect to 30-day mortality, in-hospital stroke, in-hospital MI, need of postoperative RRT, IABP, incidence of DSWI and reoperation due to bleeding.
      Several studies showed that the addition of a second arterial graft improved long-term survival and reduced the incidence of major adverse cardiac and cerebral events (MACCE) when compared with using the saphenous vein graft [
      • Chikwe J.
      • Sun E.
      • Hannan E.L.
      • Itagaki S.
      • Lee T.
      • Adams D.H.
      • et al.
      Outcomes of second arterial conduits in patients undergoing multivessel coronary artery bypass graft surgery.
      ,
      • Locker C.
      • Schaff H.V.
      • Dearani J.A.
      • Joyce L.D.
      • Park S.J.
      • Burkhart H.M.
      • et al.
      Multiple arterial grafts improve late survival of patients undergoing coronary artery bypass graft surgery: analysis of 8622 patients with multivessel disease.
      ,
      • Aboul-Hassan S.S.
      • Marczak J.
      • Stankowski T.
      • Moskal L.
      • Stanislawski R.
      • Perek B.
      • et al.
      Impact of second arterial conduit on outcomes following coronary bypass grafting.
      ,
      • Schwann T.A.
      • Hashim S.W.
      • Badour S.
      • Obeid M.
      • Engoren M.
      • Tranbaugh R.F.
      • et al.
      Equipoise between radial artery and right internal thoracic artery as the second arterial conduit in left internal thoracic artery-based coronary artery bypass graft surgery: a multi-institutional study.
      ]. A recent meta-analysis performed by Gaudino et al. supplemented those data and showed an equipoise survival outcome when comparing RITA and RA [
      • Gaudino M.
      • Lorusso R.
      • Rahouma M.
      • Abouarab A.
      • Tam D.Y.
      • Spadaccio C.
      • et al.
      Radial artery versus right internal thoracic artery versus saphenous vein as the second conduit for coronary artery bypass surgery: a network meta-analysis of clinical outcomes.
      ]. Interestingly, the most recent study performed also by Gaudino et al. showed in a pooled analysis of 10,256 CABG patients from 4 large CABG trials that the use of LITA+RA when compared to BITA is associated with improved survival (HR:0.59; 95%CI; 0.48–0.71; P = 0.001) as well as reduced MAACE (HR:0.75; 95%CI; 0.65–0.86; P = 0.02) [
      • Gaudino M.
      • Audisio K.
      • Di Franco A.
      • Alexander J.H.
      • Kurlansky P.
      • Boening A.
      • et al.
      Radial artery versus saphenous vein versus right internal thoracic artery for coronary artery bypass grafting.
      ]. Recent long-term results of the RAPCO trials (Radial Artery Patency and Clinical Outcome) showed that, at 10 years, RA was associated with reduced incidence of graft failure when compared to free RITA (HR:0.45; 95%CI; 0.23–0.88; P = 0.018) as well as reduced mortality (HR:0.53; 95%CI; 0.30–0.95; P = 0.03) [
      • Buxton B.F.
      • Hayward P.A.
      • Raman J.
      • Moten S.C.
      • Rosalion A.
      • Gordon I.
      • et al.
      Long-term results of the RAPCO trials.
      ]. Whereas Tranbaugh and colleagues [
      • Tranbaugh R.F.
      • Dimitrova K.R.
      • Lucido D.J.
      • Hoffman D.M.
      • Dincheva G.R.
      • Geller C.M.
      • et al.
      The second best arterial graft: a propensity analysis of the radial artery versus the free right internal thoracic artery to bypass the circumflex coronary artery.
      ] showed in their propensity-matched study including 528 pairs of individuals that the use of RA was a strong predictor of decreased incidence of MACCE in patients with diabetes, obesity, chronic lung disease and those older than 60 but not in terms of mortality. Schwann et al. [
      • Schwann T.A.
      • Hashim S.W.
      • Badour S.
      • Obeid M.
      • Engoren M.
      • Tranbaugh R.F.
      • et al.
      Equipoise between radial artery and right internal thoracic artery as the second arterial conduit in left internal thoracic artery-based coronary artery bypass graft surgery: a multi-institutional study.
      ] and Goldstone et al. [
      • Goldstone A.B.
      • Chiu P.
      • Baiocchi M.
      • Wang H.
      • Lingala B.
      • Boyd J.H.
      • et al.
      Second arterial versus venous conduits for multivessel coronary artery bypass surgery in California.
      ] in their PS matched study showed that RITA and RA had comparable long-term mortality. Contrarily, Shi et al. [
      • Shi W.Y.
      • Hayward P.A.
      • Tatoulis J.
      • Rosalion A.
      • Newcomb A.E.
      • Fuller J.A.
      • et al.
      Are all forms of total arterial revascularization equal? A comparison of single versus bilateral internal thoracic artery grafting strategies.
      ] showed superior survival benefit from RITA in a matched study including 318 pairs of patients when compared to RA (HR:0.78; 95%CI; 0.60–1.00; P = 0.048). Whereas Ruthmann and colleagues [
      • Ruttmann E.
      • Fischler N.
      • Sakic A.
      • Chevtchik O.
      • Alber H.
      • Schistek R.
      • et al.
      Second internal thoracic artery versus radial artery in coronary artery bypass grafting: a long-term, propensity score-matched follow-up study.
      ] reported improved survival (HR 0.23; 95% CI 0.066–0.81; P = 0.022) and reduced incidence of MACCE at follow-up (HR 0.18; 95% CI 0.08–0.42; P = 0.001) in patients receiving RITA when compared to RA. Additionally, Benedetto and colleagues [
      • Benedetto U.
      • Caputo M.
      • Gaudino M.
      • Marsico R.
      • Rajakaruna C.
      • Bryan A.
      • et al.
      Right internal thoracic artery or radial artery? A propensity-matched comparison on the second-best arterial conduit.
      ] reported on 764 propensity-matched RITA and RA, and their conclusion supported significant reduction in late mortality (HR 0.67; 95%CI; 0.48–0.96; P = 0.02). However, RITA was superior to RA when grafted to the left coronary system (HR 0.69; 95%CI; 0.47–0.99; P = 0.04) but not to the right coronary system (HR 0.98; 95%CI; 0.59–1.62; P = 0.93).
      By conducting our PS matching study with 389 pairs of patients receiving RITA or RA as second arterial graft, we managed to show comparable outcomes in terms of long-term survival and MACCE. Noteworthy, the RITA was used as in-situ graft in most patients (75%) in this study whereas in the rest as a graft connected to the LITA. In the RAPCO trials [
      • Buxton B.F.
      • Hayward P.A.
      • Raman J.
      • Moten S.C.
      • Rosalion A.
      • Gordon I.
      • et al.
      Long-term results of the RAPCO trials.
      ], RITA was used as a free graft connected to the ascending aorta as well as in 42% of the patients in the study performed by Tranbaugh and colleagues [
      • Tranbaugh R.F.
      • Dimitrova K.R.
      • Lucido D.J.
      • Hoffman D.M.
      • Dincheva G.R.
      • Geller C.M.
      • et al.
      The second best arterial graft: a propensity analysis of the radial artery versus the free right internal thoracic artery to bypass the circumflex coronary artery.
      ]. In this configuration, the caliper mismatch between ascending aorta and RITA could have an impact on its patency thereby increasing the risk of adverse events. Interestingly, Gaudino et al. [
      • Gaudino M.
      • Audisio K.
      • Di Franco A.
      • Alexander J.H.
      • Kurlansky P.
      • Boening A.
      • et al.
      Radial artery versus saphenous vein versus right internal thoracic artery for coronary artery bypass grafting.
      ] suggested in their recent study that the reason for improved clinical outcomes of RA over RITA could be technical rather than biological. Since, it has been shown that the surgeon's volume to outcome association was stronger for the RITA graft rather than for the RA and the use of RITA by less experienced surgeons is associated with increased operative mortality when compared to RA [
      • Gaudino M.
      • Bakaeen F.
      • Benedetto U.
      • Rahouma M.
      • Di Franco A.
      • Tam D.Y.
      • et al.
      Use rate and outcome in bilateral internal thoracic artery grafting: insights from a systematic review and meta-analysis.
      ,
      • Schwann T.A.
      • Habib R.H.
      • Wallace A.
      • Shahian D.M.
      • O’Brien S.
      • Jacobs J.P.
      • et al.
      Operative outcomes of multiple-arterial versus single-arterial cor-onary bypass grafting.
      ,
      • Schwann T.
      • Habib R.
      • Wallace A.
      • Shahian D.
      • Gaudino M.
      • Kurlansky P.
      • et al.
      Bilateral internal thoracic artery versus radial artery multi-arterial by-pass grafting: a report from the STS database.
      ]. In our study, 67.5% of the whole study population received RITA and most surgeons performing multiple arterial grafts at those centers are dedicated surgeons to such type of procedures and are experienced surgeons in RITA as well as RA harvesting, thereby resulting in low operative mortality and comparable long-term clinical outcomes between both RITA and RA.
      Meta-analysis performed by Gaudino et al. [
      • Gaudino M.
      • Lorusso R.
      • Rahouma M.
      • Abouarab A.
      • Tam D.Y.
      • Spadaccio C.
      • et al.
      Radial artery versus right internal thoracic artery versus saphenous vein as the second conduit for coronary artery bypass surgery: a network meta-analysis of clinical outcomes.
      ] showed that the use of RITA was associated with increased risk of DSWI but not when RA was grafted. In our study, there was no difference between RITA and RA in terms of DSWI. This was probably due to the fact that around 55% of the patients had skeletonized BITA and it was shown that DSWI could be reduced by using skeletonized technique [
      • Gaudino M.
      • Lorusso R.
      • Rahouma M.
      • Abouarab A.
      • Tam D.Y.
      • Spadaccio C.
      • et al.
      Radial artery versus right internal thoracic artery versus saphenous vein as the second conduit for coronary artery bypass surgery: a network meta-analysis of clinical outcomes.
      ,
      • Sá M.P.
      • Cavalcanti P.E.
      • de Andrade Costa Santos H.J.
      • Soares A.F.
      • Albuquerque Miranda R.G.
      • Araújo M.L.
      • et al.
      Skeletonized versus pedicled bilateral internal mammary artery grafting: outcomes and concerns analyzed through a meta-analytical approach.
      ,
      • Sá M.P.
      • Ferraz P.E.
      • Escobar R.R.
      • Vasconcelos F.P.
      • Ferraz A.A.
      • Braile D.M.
      • et al.
      Skeletonized versus pedicled internal thoracic artery and risk of sternal wound infection after coronary bypass surgery: meta-analysis and meta-regression of 4817 patients.
      ].
      The ongoing Randomization of Single vs Multiple Arterial Grafts (ROMA) trial (NCT03217006) will hopefully provide a further evidence to this debate [
      • Gaudino M.
      • Alexander J.H.
      • Bakaeen F.G.
      • Ballman K.
      • Barili F.
      • Calafiore A.M.
      • et al.
      Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial-rationale and study protocol.
      ]. This large trial aims on comparing a multiple vs single arterial strategy with target sample size of 4300 patients with left main disease or multivessel coronary artery disease in whom the second arterial graft is either a second ITA or a RA. The choice of the second arterial graft is according to surgeon's decision. This study for sure will provide a further evidence to this debate which will allow a comparison of the RA and RITA, however still as a post-hoc analysis.
      The present study has several limitations. The main limitation is the lack of randomization. To reduce the impact of potential confounders, a PS-matching procedure was performed. However, it should be noted that even in a well-balanced PS matching study, the results could reflect the effects of unknown or unmeasured confounders. A further limitation is that the subgroup analysis was derived from the matched cohorts which may have residual imbalances. Surgeons performance may still be a confounding factor despite the fact that most surgeons performing multiple arterial grafts at those centers are dedicated surgeons to such type of procedures. However the ongoing On the other hand, we included Medinet Heart Center with total 2.7% MAG rate only due to the fact that Medinet Heart Center in Nowa Sol and in Wroclaw are closely affiliated as part of Medinet Heart Center and the majority of the MAG surgeries performed at Medinet Heart Center Wroclaw were performed by dedicated surgeons from Medinet Heart Center Nowa Sol. Lastly, no data were available regarding graft patency and the need for repeated revascularization at follow-up. It is noteworthy that by matching the RITA group to the RA group, the resulting conclusions are relevant to subjects in whom RA was selected. The results may not generalize to subjects with a profile more similar to the RITA group (slightly younger, more male, lower BMI, less comorbidities, more LM disease and non-elective surgery).

      5. Conclusion

      In the present study, we found that the use of right internal thoracic artery or radial artery as second arterial conduit during CABG with internal thoracic artery to the LAD is safe and associated with comparable long-term clinical outcomes. The choice of optimal second arterial conduit should be guided mainly by patients' characteristics and surgeons' preferences.

      Author contributions

      Study concept and design: S.S.A; acquisition of data: S.S.A, B.P, A.O, T.U, L.M and W.M.; analysis and interpretation of data: S.S.A,J.M, M.P.S and A.K.A; drafting of the manuscript: S.S.A,T.S, B.P, M.P.S; critical revision of the manuscript: S.S.A, B.P M.J, G.T, B.R and RC All authors have read and agreed to the published version of the manuscript.

      Institutional Review Board statement

      The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Ethics Committee of Medinet Heart Center (S-817/2021, 12/12/2021) and Poznan University of Medical Sciences (P-520/2022, 15/01/2022).

      Informed consent statement

      Individual patient consent was waived because of the study's retro-spective design and the data collection from routine care.

      Disclosures

      Sleiman Sebastian Aboul-Hassan has recieved financial support from Getinge and serves as a EVH consultant for Getinge in Poland. Basel Ramlawi has received financial support from Medtronic, Corcym, and AtriCure. These conflicts are unrelated to this study. Rest of the authors have nothing to disclose.

      Appendix A. Supplementary data

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