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. 2020 Sep 10;15(9):e0238880. doi: 10.1371/journal.pone.0238880

Off-pump versus on-pump coronary artery surgery in octogenarians (from the KROK Registry)

Piotr Knapik 1,*, Grzegorz Hirnle 2, Anetta Kowalczuk-Wieteska 2, Michał OZembala 2, Szymon Pawlak 2, Tomasz Hrapkowicz 2, Piotr Przybyłowski 3,4, Paweł Nadziakiewicz 1, Daniel Cieśla 5, Bartłomiej Perek 6, Bogusław Kapelak 7, Marek Cisowski 8, Jan Rogowski 9, Edward Pietrzyk 10, Zdzisław Tobota 11, Marian Zembala 2; on behalf of KROK Investigators
Editor: Mariusz Kowalewski12
PMCID: PMC7482977  PMID: 32913359

Abstract

Background

According to the medical literature, both on-pump and off-pump coronary artery surgery is safe and effective in octogenarians.

Objectives

The aim of our study was to examine the epidemiology, in-hospital outcomes and long-term follow-up results in octogenarians undergoing off-pump and on-pump coronary artery surgery utilizing nationwide registry data.

Methods

All octogenarians (≥ 80 years) enrolled in the Polish National Registry of Cardiac Surgical Procedures (KROK Registry), who underwent isolated coronary surgery between January 2006 and September 2017 were identified. Preoperative data, perioperative complications, hospital mortality and long-term mortality were analyzed. Unadjusted and propensity-matched comparisons were performed between octogenarians undergoing off-pump and on-pump coronary artery bypass surgery.

Results

Octogenarians accounted for 4.1% of the total population undergoing coronary artery surgery in Poland during the analyzed period (n = 152,631) and this percentage is increasing. Among 6,006 analyzed patients, 2,744 (45.7%) were operated on-pump and 3,262 (54.3%) were operated off-pump. Propensity-matched analysis revealed that patients operated on-pump were more often reoperated due to postoperative bleeding and their in-hospital mortality was higher (6.6% vs 4.5%, p = 0.006 and 8.7% vs 5.8%, p = 0.001, respectively). Long-term all-cause mortality was lower among patients operated off-pump (p = 0.013).

Conclusion

On the basis of our findings we suggest that off pump technique should be considered as perfectly acceptable in octogenarians.

Introduction

In the industrialized world, the average life expectancy continues to increase. Cardiac surgery is confronted with a growing population of octogenarians with coronary artery disease and clear indications for coronary artery surgery [1].

Patients over 80 years old are more prone to increased postoperative morbidity and mortality, because of more frequent comorbid risk factors and frailty [2, 3]. This population requires special care, attention, and treatment. Off-pump coronary artery bypass (OPCAB) grafting gives the surgeon the opportunity to avoid the inherent risks associated with coronary artery bypass surgery (CABG) with cardiopulmonary bypass. These increased risks include hemodilution, global myocardial ischemia, nonpulsatile arterial flow, systemic inflammatory response, and atherosclerotic embolization from aortic manipulation [4].

The debate concerning the superiority of OPCAB over CABG (and vice versa) has continued for many years [4, 5]. Proponents of the OPCAB technique have advocated for its specific use in octogenarians since the beginning of this debate [6] and many studies continue to evaluate the potential benefit [7]. Evidence from meta-analyses indicates that utilizing the off-pump technique significantly reduces stroke, renal failure, ventilation time, atrial fibrillation, transfusion requirements, and postoperative length of stay when compared with conventional CABG using cardiopulmonary bypass [8, 9]. In spite of these promising results, well-designed randomized controlled trials have been unable to consistently demonstrate such benefits [5, 10] and some trials have even cast doubt on the long-term benefit of OPCAB in terms of graft patency [11].

In higher risk octogenarian patients, there is potential for more tangible clinical benefit when cardiopulmonary bypass is avoided [12]. In contrast to this, the most discussed potential benefit of on-pump technique has always been the potential for higher long-term graft patency [11]. But is long-term graft patency really a key issue for octogenarians?

The aim of this retrospective study was to compare the perioperative and long-term results of octogenarians undergoing OPCAB and CABG using data from the nationwide Polish National Registry of Cardiac Surgical Procedures (KROK Registry).

Methods

Study design

This analysis is based on data from the Polish National Registry of Cardiac Surgical Operations (KROK Registry), a joint initiative of the Polish Society of Cardiothoracic Surgeons and the Polish Ministry of Health. Details regarding the KROK Registry and the collection of follow-up data have been previously described [13]. Due to the retrospective and anonymous nature of the study, Ethical Committee of the Medical University of Silesia in Katowice waived the need for consent of the patients to participate in the study.

Our study included all octogenarians (≥ 80 years) who underwent isolated coronary artery surgery in Poland between January 2006 and September 2017 (11 years and 9 months). Patients undergoing Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) and patients in whom the type of coronary surgery could not be clearly determined, were excluded. The remaining population of octogenarians undergoing isolated coronary artery surgery was divided into two groups: patients who underwent surgery either on-pump or off-pump (Fig 1). Conversions from OPCAB do CABG were analyzed in the OPCAB group.

Fig 1. Patients’ flow through the study.

Fig 1

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To enhance statistical comparison between the groups, the overall population of patients undergoing CABG and OPCAB was then restricted to propensity-matched groups.

The primary outcomes of this study were the in-hospital mortality rate and the incidence of perioperative complications. The secondary outcome was all-cause mortality in a long-term follow-up period.

Each patient was described in terms of baseline demographic data, circulatory function, individual risk factors, general condition directly before the procedure, and procedure-related variables (Table 1).

Table 1. Comparison of preoperative variables in all patients (left) and propensity-matched patients (right).

All patients 80+ Matched patients 80+
Group of variables Variable CABG OPCAB p z-diff CABG OPCAB p z-diff
(n = 2,744) (n = 3,262) (n = 1,813) (n = 1,813)
Demographic data Age>90 years 155 (5.6%) 222 (6.8%) 0.074 -1.86 112 (6.2%) 116 (6.4%) 0.837 -0.27
Age 86–90 years 8 (0.3%) 16 (0.5%) 0.311 -1.24 8 (0.4%) 8 (0.4%) 0.802 0.00
Female gender 941 (34.3%) 1187 (36.4%) 0.096 -1.69 643 (35.5%) 636 (35.1%) 0.835 0.24
Circulatory function CCS class IV 588 (21.4%) 645 (19.8%) 0.121 1.58 368 (20.3%) 363 (20.0%) 0.868 0.21
NYHA class III or IV 451 (16.4%) 522 (16.0%) 0.675 0.45 282 (15.6%) 295 (16.3%) 0.586 -0.59
Recent MI<90 days 908 (33.1%) 923 (28.3%) 0.000 4.01 566 (31.2%) 589 (32.5%) 0.433 -0.82
Pulmonary hypertension 5 (0.2%) 17 (0.5%) 0.051 -2.26 5 (0.3%) 4 (0.2%) 1.000 0.33
LVEF <30% 90 (3.3%) 92 (2.8%) 0.337 1.03 47 (2.6%) 52 (2.9%) 0.684 -0.51
Previous PCA/stent 628 (22.9%) 597 (18.3%) 0.000 4.37 378 (20.8%) 382 (21.1%) 0.903 -0.16
Persistent or chronic AF 249 (9.1%) 335 (10.3%) 0.130 -1.57 184 (10.1%) 197 (10.9%) 0.516 -0.70
Left main stem lesion 1166 (42.5%) 973 (29.8%) 0.000 10.23 677 (37.3%) 683 (37.7%) 0.864 -0.21
Triple vessel disease 1876 (68.4%) 1422 (43.6%) 0.000 19.95 1056 (58.2%) 1090 (60.1%) 0.265 -1.15
Individual risk factors Cigarette smoking 82 (3.0%) 130 (4.0%) 0.044 -2.11 66 (3.6%) 75 (4.1%) 0.492 -0.77
Hypercholesterolaemia 1598 (58.2%) 1771 (54.3%) 0.002 3.07 1055 (58.2%) 1084 (59.8%) 0.344 -0.98
Diabetes mellitus 879 (32.0%) 1117 (34.2%) 0.075 -1.81 655 (36.1%) 643 (35.5%) 0.703 0.42
Arterial hypertension 2438 (88.8%) 2613 (80.1%) 0.000 9.49 1631 (90.0%) 1631 (90.0%) 0.956 0.00
BMI>35 kg/m2 71 (2.6%) 78 (2.4%) 0.686 0.49 51 (2.8%) 51 (2.8%) 0.920 0.00
Renal failure 379 (13.8%) 437 (13.4%) 0.667 0.47 262 (14.5%) 274 (15.1%) 0.607 -0.56
COPD 173 (6.3%) 209 (6.4%) 0.913 -0.16 120 (6.6%) 124 (6.8%) 0.842 -0.27
Past TIA. RIND, stroke 123 (4.5%) 123 (3.8%) 0.186 1.38 73 (4.0%) 70 (3.9%) 0.865 0.26
Past treatment of CAD 30 (1.1%) 28 (0.9%) 0.427 0.92 20 (1.1%) 19 (1.0%) 1.000 0.16
PVD 352 (12.8%) 349 (10.7%) 0.012 2.54 202 (11.1%) 210 (11.6%) 0.714 -0.42
Poor mobility 113 (4.1%) 175 (5.4%) 0.028 -2.28 81 (4.5%) 87 (4.8%) 0.693 -0.47
Condition before the procedure Cardiogenic shock 101 (3.7%) 207 (6.3%) 0.000 -4.78 81 (4.5%) 69 (3.8%) 0.359 1.00
Use of IABP 87 (3.2%) 55 (1.7%) 0.000 3.68 36 (2.0%) 43 (2.4%) 0.495 -0.80
IV nitrates or heparin. 479 (17.5%) 540 (16.6%) 0.372 0.93 297 (16.4%) 315 (17.4%) 0.451 -0.80
Procedure-related variables Previous cardiac surgery 41 (1.5%) 39 (1.2%) 0.372 1.00 24 (1.3%) 26 (1.4%) 0.887 -0.28
Non-elective surgery 1175 (42.8%) 1438 (44.1%) 0.339 -0.98 803 (44.3%) 826 (45.6%) 0.463 -0.77
Complete arterial revascularization 95 (3.5%) 897 (27.5%) 0.000 -28.08 93 (5.1%) 107 (5.9%) 0.344 -1.02
Number of grafts 1 graft 85 (3.1%) 838 (25.7%) 0.000 -27.11 83 (4.6%) 93 (5.1%) 0.487 -0.77
2 grafts 1046 (38.1%) 1345 (41.2%) 0.015 -2.46 898 (49.5%) 904 (49.9%) 0.868 -0.20
3 or more grafts 1613 (58.8%) 1079 (33.1%) 0.000 20.57 832 (45.9%) 816 (45.0%) 0.617 0.53
Year of surgery 2006–2009 588 (21.4%) 632 (19.4%) 0.053 1.97 341 (18.8%) 344 (19.0%) 0.932 -0.13
2010–2013 1100 (40.1%) 1279 (39.2%) 0.505 0.69 699 (38.6%) 711 (39.2%) 0.708 -0.41
2014–2017 1056 (38.5%) 1351 (41.4%) 0.022 -2.31 773 (42.6%) 758 (41.8%) 0.638 0.50
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Abbreviations: AF–atrial fibrillation, CAD–carotid artery, CCS–Canadian Coronary Score, COPD–chronic obstructive pulmonary disease, IABP–intra-aortic balloon pump, IV–intravenous, LVEF—Left Ventricular Ejection Fraction, MI–myocardial infarction, NYHA–New York Heart Association, PCA–percutaneous coronary angioplasty, PVD–peripheral vascular disease, RIND–reversible ischaemic neurologic deficit, SR–surgical reexploration, TIA–transient ischaemic attack.

Assessment of complications

Patients who developed postoperative complications were identified. Neurological complications were defined to include patients who developed a new neurological deficit in the postoperative period with persistent symptoms still present at the time of the hospital discharge. Respiratory complications included patients who required prolonged mechanical ventilation for more than 24 hours, and/or patients who developed pneumonia in the postoperative period. Renal complications included patients who required any form of renal replacement therapy in the postoperative period. Gastrointestinal complications included patients with gastrointestinal bleeding, pancreatitis, cholecystitis, and/or mesenteric ischemia—with or without a surgical intervention. Sternal, mediastinal or wound infection included all types of surgical site infections of the sternum. Perioperative myocardial infarction was recognized according to the criteria used by the Society of Thoracic Surgeons adult cardiac surgery database. Mechanical circulatory support was broadly defined to include the use any of the available options in this field. ICU readmission was identified if a patient was transferred to the ICU again following a previous discharge from this unit, during the same hospital admission.

Statistical analysis

Continuous variables were presented as mean and standard deviation, while categorical variables were presented as percentages. Chi-squared, Mann-Whitney U and t-Student tests were used to assess for statistical significance where appropriate. Patients for comparison were matched to achieve the similar preoperative status. The data were matched with the Greedy data matching algorithm using Mahalanobis distance within propensity score calipers. Each caliper radius was set to 0.2*Sigma. Propensity score was calculated using logistic regression. We used all variables from Table 1. To assess the covariate balance, z-difference coefficients were calculated for each variable before and after matching. The mean value before and after the matching was 0.28 and -0.30, and the variance was 79.31 and 0.32, respectively.

Assessment of long-term follow-up data included analysis of all-cause mortality. The National Health Fund death database was searched for all patients included in this study from the date of their procedure until 30th of September 2017. These data were then analyzed using the Kaplan-Meier method with stratified log-rank testing. For the purpose of the principal analysis, the date of operation was considered the starting point. For the purpose of the additional censored analysis, the day of hospital discharge was considered the starting point. Completness of follow-up data was calculated according to the method described by Wu et. al. [14].

For all analyses, a two-tailed p-value <0.05 was considered statistically significant. The analyses and graphs were performed with the use of Dell Inc. (2016). Dell Statistica (data analysis software system, version 13) and R version 3.6.1 2019 (the R Foundation for Statistical Computing).

Results

Overall, 152,631 adult patients underwent isolated coronary artery surgery in Poland during the study period of 11 years and 9 months and were included in the KROK Registry. There were 6,276 octogenarians in this population (4.1%). Among 6,276 octogenarians, there were 270 patients who were excluded (4.3%), because they either underwent the MIDCAB procedure or their type of coronary surgery could not be clearly determined. The remaining 6,006 patients were divided into two groups. The on-pump group consisted of 2,744 patients (45.7%) and the off-pump group consisted of 3,262 patients (54.3%). There were 53 conversions from OPCAB to CABG in the OPCAB group. The mean age of this population was 82.0 years (range 80 to 96 years). Completeness of follow-up data according to Clark’s C-index was 78.6% and the modified C*-index was 88.8%. Patients’ flow through the study has been shown in Fig 1.

Epidemiology

The overall percentage of octogenarians steadily increased during the study period, from 1.7% in 2006, to 5.9% in 2015, when a plateau was observed. The total number of coronary artery surgery procedures in Poland remained relatively constant throughout these years but recently started to gradually decrease (Fig 2).

Fig 2. All coronary artery surgery procedures in Poland over a period of 11 years (2006–2016) and the amount of octogenarians in this population.

Fig 2

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Comparison of groups

Patients operated on-pump were younger in comparison to those operated off-pump (mean 81.9 ± 2.0 years vs 82.1 ± 2.1 years, p = 0.046). Mean EuroSCORE II values (assessed in all patients since 2012) before matching were found to be significantly higher in patients operated on-pump (4.7 ± 5.8% vs 4.3 ± 5.8%, p<0.001, respectively). Patients operated on-pump generally had more advanced atherosclerosis, as evidenced by a higher incidence of atherosclerosis-related co-morbidities (Table 1).

The on-pump group received a higher mean number of grafts compared to the off-pump group (2.67 ± 0.72 vs 2.16 ± 0.94, p<0.001). Consequently, the mean operative time was significantly longer in patients operated on-pump (3.54 ± 1.23 vs 3.30 ± 1.34 hours, p<0.001). A significantly higher proportion of patients operated on-pump had a procedure time exceeding 3 hours (59.2% vs 51.5%, p<0.001).

The overall time of postoperative ventilation (available in 68.5% of patients in the on-pump and in 63.8% of patients in the off-pump group) was significantly longer for the on-pump group (20.8 ± 47.6 hours vs 15.3 ± 36.8 hours, p<0.001), with a median value of 11.2 vs 9.4 hours, respectively. The percent of patients with postoperative ventilation exceeding 24 hours was significantly higher in patients operated on-pump (11.1% vs 7.5%, p<0.001).

The on-pump group had a higher incidence of major postoperative complications except for neurological complications, renal failure and sternal or wound infection. In addition to this, the in-hospital mortality rate was significantly higher for patients undergoing the on-pump procedure. This result was similar when conversions were analyzed both in the OPCAB group (8.1% vs 5.4%, p<0.001) (Table 2) and in the CABG group (8.5% vs 5.0%, p<0.001).

Table 2. Comparison of postoperative complications in all patients (left) and in propensity-matched patients (right).

All patients Matched patients
Postoperative course CABG OPCAB p CABG OPCAB p
(n = 2,744) (n = 3,262) (n = 1,813) (n = 1,813)
Conversion 0 (0%) 53 (1.6%) - 0 (0%) 41 (1.1%) -
Neurological complications 68 (2.5%) 60 (1.8%) 0.106 46 (2.5%) 38 (2.1%) 0.440
Respiratory complications 205 (7.5%) 158 (4.8%) 0.000 134 (7.4%) 102 (5.6%) 0.037
Gastrointestinal complications 46 (1.7%) 35 (1.1%) 0.056 33 (1.8%) 25 (1.4%) 0.354
Renal complications 119 (4.3%) 141 (4.3%) 0.971 74 (4.1%) 90 (5.0%) 0.231
Sternal, mediastinal or wound infection 59 (2.2%) 63 (1.9%) 0.612 37 (2.0%) 35 (1.9%) 0.905
Perioperative myocardial infarction 41 (1.5%) 27 (0.8%) 0.021 25 (1.4%) 17 (0.9%) 0.277
Mechanical circulatory support 122 (4.4%) 109 (3.3%) 0.032 78 (4.3%) 70 (3.9%) 0.557
ICU readmission 31 (1.1%) 46 (1.4%) 0.397 24 (1.3%) 30 (1.7%) 0.493
Reoperation due to bleeding 184 (6.7%) 138 (4.2%) <0.001 120 (6.6%) 81 (4.5%) 0.006
In-hospital death 221 (8.1%) 177 (5.4%) <0.001 157 (8.7%) 106 (5.8%) 0.001
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The overall rate of ICU readmissions was similar (1.1% vs 1.4%, p = 0.397). Mean length of hospital stay was similar in both groups (12.3 ± 8.7 days vs 12.1 ± 8.1 days, p = 0.18), with a similar proportion of patients staying in the hospital longer than two weeks (22.8% vs 23.1%, p = 0.846, respectively).

The mean overall follow-up was 3.6 ± 2.9 years (0–11.7 years) for patients operated on-pump and 3.6 ± 2.8 years (0–11.7 years) for patients operated off-pump. The overall total mortality rate for these groups was 37.2% vs 35.6%, respectively (p = 0.185). Kaplan-Meier estimate of mortality in subsequent time intervals in the first year of the follow-up is presented on a left side of Table 3. Kaplan–Meier follow-up curves for all-cause mortality are presented on a left side of Fig 4. The principal analysis (starting at the day of operation) indicated that long-term all-cause mortality was similar in both groups (p = 0.157). Additional censored analysis (starting at the day of hospital discharge) indicated that long-term all-cause mortality was also similar in both groups (p = 0.232) (see S1A Fig to this manuscript).

Table 3. Estimated mortality in subsequent time intervals following hospital discharge in the first year of the follow-up period in all patients (left) and propensity-matched patients (right).

All patients Matched patients
CABG OPCAB p CABG OPCAB p
(n = 2,744) (n = 3,262) (n = 1,813) (n = 1,813)
In-hospital mortality 221 (8.1%) 177 (5.4%) <0.001 157 (8.7%) 106 (5.8%) 0.001
Discharge (days)
30 54 (2.2%) 64 (2.1%) 0.928 31 (1.9%) 31 (1.8%) 0.997
31–60 64 (2.6%) 55 (1.8%) 0.060 42 (2.6%) 31 (1.9%) 0.183
61–90 28 (1.2%) 28 (1.0%) 0.506 21 (1.4%) 13 (0.8%) 0.184
91–180 28 (1.2%) 62 (2.2%) 0.012 21 (1.4%) 31 (2.0%) 0.282
181–270 33 (1.5%) 43 (1.6%) 0.871 20 (1.4%) 11 (0.7%) 0.113
270–365 25 (1.2%) 38 (1.5%) 0.459 18 (1.3%) 20 (1.4%) 0.990
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Fig 4.

Fig 4

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Probability of survival in octogenarians undergoing CABG and OPCAB surviving hospital stay: (A)–all patients, (B)–propensity-matched patients.

Comparisons of propensity-matched groups

The mean age of propensity-matched groups was similar for on-pump and off-pump coronary artery surgery (82.0 ± 2.1 years vs 82.0 ± 2.1 years, p = 0.30). Mean EuroSCORE II values were similar in both groups (4.5 ± 5.4% vs 4.3 ± 5.6%, p = 0.103, respectively). Following the propensity-matching procedure, all preoperative differences in patients’ baseline demographics became non-significant (Table 1).

Following propensity-score matching, patients operated on-pump received a similar mean number of grafts compared to the off-pump group (2.48 ± 0.71 grafts vs 2.51 ± 0.78 grafts, p = 0.930). The mean operative time following matching was similar in both groups (3.49 ± 1.24 hours vs 3.43 ± 1.29 hours, p = 0.066), as was the proportion of patients whose procedural time exceeded 3 hours (58.0% vs 56.0%, p = 0.248).

The total time of postoperative ventilation (available in 71.1% of patients in the on-pump group and in 67.3% of patients in the off-pump group) was longer among patients operated on-pump (20.3 ± 49.0 hours vs 15.2 ± 38.5 hours, p<0.001), with a median value of 11.7 vs 9.3 hours, respectively. The percentage of patients with postoperative ventilation exceeding 24 hours was significantly higher in the on-pump cohort (10.9% vs 8.1%, p = 0.019). A graphical comparison of propensity-matched patients remaining ventilated in consecutive postoperative hours has been additionally expressed in the form of a Kaplan-Meier curve (Fig 3).

Fig 3. Kaplan-Meier curves for octogenarians remaining ventilated following CABG and OPCAB in a propensity-matched patients.

Fig 3

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Following propensity-matching, the incidence of postoperative respiratory complications and reoperation due to bleeding was higher in the on-pump group. In-hospital mortality also remained significantly higher in the CABG group. This result was similar when conversions were analyzed both in the OPCAB group (8.7% vs 5.8%, p = 0.001) (Table 2) and in the CABG group (9.3% vs 5.1%, p<0.001). The average hospital length of stay and the proportion of patients with a hospital stay longer than two weeks was similar in a both groups (12.3 ± 8.8 days vs 12.3 ± 8.2 days, p = 0.74 and 22.5% vs 24.1%, p = 0.270, respectively).

The mean follow-up period was 3.4 ± 2.8 years (range 0–11.7 years) for patients operated on-pump and 3.6 ± 2.7 years (range 0–11.7 years for patients operated off-pump). The overall mortality rate for these groups was 36.1% vs 33.9%, respectively (p = 0.175). Kaplan-Meier estimate of mortality in subsequent time intervals in the first year of the follow-up is presented on a right side of Table 3. Kaplan–Meier follow-up curves for all-cause mortality are presented on a right side of Fig 4. The principal analysis (starting at the day of operation) indicated that long-term all-cause mortality was lower in the OPCAB group (p = 0.013). Additional censored analysis (starting at the day of hospital discharge) indicated however, that long-term all-cause mortality was similar in both groups (p = 0.362) (see S1B Fig to this manuscript)

Discussion

Our findings suggest that octogenarians constitute a high-risk population and the off-pump procedure appears superior among patients scheduled for isolated coronary artery bypass surgery for these patients in terms of in-hospital results. Utilization of the on-pump technique resulted in significantly higher in-hospital mortality (8.7% vs 5.8%, p<0.001) and higher all-cause mortality in the long-term follow-up period (p = 0.013). The increased in-hospital mortality was likely due to the higher incidence of postoperative complications (mainly reoperation due to bleeding) in the on-pump group. Similar conclusions were drawn by Hulde et al. who observed that the duration of mechanical ventilation, intensive care unit stay, the risk of stroke, in-hospital mortality and 30-day mortality were significantly lower in the off-pump group than in the on-pump group [15].

Comparative findings reported in the literature are contradictory. One recent retrospective study, analyzing 134,117 discharge records from 797 US hospitals, found that in-hospital mortality did not differ between octogenarians who underwent CABG and OPCAB (5.5% vs. 5.2%, p = 0.3) [16]. At the same time, a recent systematic review based on 16 retrospective studies (performed in 27,623 octogenarians overall) found that the OPCAB technique was associated with significantly lower in-hospital mortality [9]. The other large study, a US register analysis by Chikwe et al., reported higher mortality over 10-years of follow-up in the off-pump versus on-pump group [17].

With respect to prospective studies, Diegeler et al. recently published the long-term results of the European GOPCABE trial on 2,539 patients aged 75+ who underwent coronary surgery in Germany between 2008 and 2011 [11]. The study found no significant difference between CABG and OPCAB with respect to the 5-year survival rates and the combined outcome of death, myocardial infarction, and repeat revascularization [11]. An earlier interim report from the same population confirmed similar short term results in these two groups [5]. In the prospective, European DOORS trial, Houlind et al. also found that OPCAB technique was non-inferior to CABG in a group of patients aged 70+ [1], despite lower graft patency [10].

In Europe, there are only a few retrospective studies comparing the results of CABG and OPCAB in octogenarians with an appropriate sample size [9]. Based on our review of the literature, our study currently represents the largest (and most contemporary) analysis of octogenarians undergoing coronary surgery in Europe. It is also worth emphasizing that our study comes from a geographical area with only few available data in this field so far, where a rapid increase in the number of cardiac surgical procedures is occurring [13].

According to the KROK database, the overall proportion of octogenarians undergoing coronary artery surgery has been steadily increasing from 1.7% of all coronary artery procedures in 2006 to 5.9% in 2015. These findings are consistent with the trends reported in other countries. For example, octogenarians comprised 8.2% of a contemporary US population scheduled for isolated coronary surgery [7]. The recently observed plateau with further decline may be related to the rapid advances in non-surgical therapies, including implantation of drug-eluting stents and the implementation of newer anticoagulant and antiplatelet medications in combination with aggressive lipid-lowering therapy. These advances clearly improve the results of less invasive treatment of patients with coronary artery disease [9, 18]. Among those octogenarians who still undergo surgery, the percentage of on-pump and off-pump procedures is currently very similar.

The decision regarding surgical technique is always the surgeon’s individual decision. In our study, Polish octogenarians operated on-pump were found to have a higher rate of advanced atherosclerosis. Opposite trends might be found in a retrospective analysis performed by Cavallaro et al. based on the largest publicly available database of inpatient hospital care in the US, where data of 187,366 patients undergoing CABG and 69,779 patients undergoing OPCAB were compared (all ages, octogenarians included) [19]. Patients undergoing OPCAB differed preoperatively from those scheduled for on-pump surgery. The strongest independent predictors of off-pump use were the presence of aortic atherosclerosis, liver disease and renal failure; whereas, patients with diabetes, previous myocardial infarction, previous cardiac surgery or percutaneous coronary intervention were more likely to undergo on-pump surgery [19]. Because the study did not assess these factors by age, it is impossible to know whether a similar trend was present for octogenarian patients. Moreover, the Cavallaro study was based on patients who underwent surgery from 2005–2010, and our data come from the years 2006–2017 (with the majority of octogenarians scheduled for surgery after 2010).

The literature regarding the demographic characteristics of patients who undergo off-pump and on-pump surgery is inconsistent. Benedetto et al. observed a higher percentage of patients with peripheral vascular disease, chronic pulmonary disease and congestive heart failure among 137,117 octogenarians who underwent OPCAB in comparison to patients undergoing CABG [16]. These findings were not replicated in a 2015 systematic review of 9,744 CABG and 8,566 OPCAB patients [12], or in the preoperative data previously presented by LaPar et al. [20]. Significant differences have been also observed between countries [21]. Therefore, an overall, cohesive assessment of the differences between patients operated with the use of CABG or OPCAB technique is not possible given the current state of the literature.

Both unadjusted and propensity-matched analyses revealed that on-pump myocardial revascularisation in Polish octogenarians was associated with more frequent postoperative complications, with the resulting increased in-hospital mortality. Patients operated on-pump were more frequently reoperated due to bleeding–this difference was particularly striking and independent of propensity matching. Respiratory complications such as prolonged postoperative ventilation (over 24h) also appeared more frequently in the CABG group. Both complications are well-known to affect in-hospital mortality [13].

The association between reoperation due to bleeding and overall survival has previously been described by our group [13]. Additionally, the increased frequency of respiratory complications among our patients operated on-pump is likely related to their prolonged times of postoperative ventilation. In a recent prospective randomized trial, patients operated on-pump also had a ventilation time twice as long as their counterparts operated off-pump [22].

In a previously mentioned Nationwide Inpatient Sample study, the authors reported a higher rate of stroke among octogenarians operated on-pump [16]. The same difference was noted in a recent systematic review concentrating on stroke rates among octogenarians undergoing coronary surgery [12]. In our study, it should be noted that the difference in the incidence of neurological complications was significant in an unadjusted comparison, but there was no statistically significant difference after propensity-matching.

Other factors analyzed in our study, such as renal complications, wound infections, and ICU readmissions did not reach statistical significance. In terms of renal failure, our results underscore previous studies based on large databases and meta-analyses, which also reported no statistical difference in the rate of renal replacement therapy among octogenarians in these two groups [16, 23].

Our follow-up results contrast with the conclusions of both the GOPCABE and DOORS trials, where long-term survival was similar also when taking in-hospital death into account [10, 11]. It should be noted however, that patients included in both these trials were younger (75+ and 70+, respectively). These studies were also not based on registry data.

In our study, octogenarians operated on-pump received a higher mean number of grafts. This difference clearly influenced the mean operative time as well as the proportion of patients with a procedural time exceeding 3 hours. The advantage of CABG regarding the number of grafts is supported by nearly every study comparing CABG and OPCAB; however, the ROOBY trial indicated that the number of grafts initially planned per patient was the same in both groups [24]. The CORONARY trial concluded that incomplete revascularisation was similar in both groups (10% for on-pump vs. 11.2% for off-pump; P = 0.05) [25]. In our study, the OPCAB group received a lower number of grafts with a similar long-term survival (among survivors of the hospital stay).

Interestingly, we observed that octogenarians scheduled for off-pump surgery were more likely to be diagnosed with cardiogenic shock or to be on pharmacological inotropic support, but the pre-procedural intra-aortic balloon pump was more frequently inserted in the on-pump group. There was however, a higher incidence of significant left main stem lesion in the CABG group and preoperative implantation of an intra-aortic balloon pump in such patients is a standard of care in many Polish centers [26, 27].

Our findings based on data from the KROK registry represent the real-life results of coronary surgery in Polish octogenarians, but it has long been known that there is a considerably lower risk of in-hospital mortality in these patients when they are operated off-pump [18]. Moreover, it is also worth mentioning, that the advantage of OPCAB in Polish octogenarians has been just confirmed in a subgroup of patients with specific co-morbidity [28]. Kowalczuk et al. [28] noticed, that among patients with significant left main stenosis, in-hospital mortality was higher only when the procedure was performed on-pump. This difference proved to be significant despite the fact, that sample size in this study was significantly lower, only patients with records indicating preoperative significant left main stenosis were analyzed and the analyzed period was shorter by almost two years [28].

Such strong scientific evidence should lead to careful evaluation of the optimal method of revascularization of octogenarians in Poland. This is also a situation when locally obtained, retrospective data are of great practical importance.

Our study has some important limitations. The study was observational and therefore not randomized and prone to bias. Surgeons’ rationale for selection of either the CABG or OPCAB technique in various centers is unknown. It is also important to note that the source of our data is heterogenous. Some of our data come from centers where beating heart surgery is widely used, and therefore the OPCAB technique might be more successful due to a learning curve effect. Because our study utilized registry data, we were strictly limited to the data available in KROK Registry [13]. Finally, our follow-up analysis was limited to all-cause mortality, without the necessary detail to assess whether an octogenarian’s death was secondary to the coronary surgery or an unrelated cause.

Based on the results of this study, we suggest that the OPCAB technique should be considered as perfectly acceptable in octogenarians when performed by surgeons experienced in the technique. In these high-risk patients, this technique appears to offer a lower perioperative mortality rate, a lower rate of major perioperative adverse events and better long-term survival.

Supporting information

S1 File

(XLS)

Click here for additional data file. (72KB, xls)
S2 File

(XLSX)

Click here for additional data file. (149.2KB, xlsx)
S1 Fig

(JPG)

Click here for additional data file. (2.4MB, JPG)

Acknowledgments

The authors wish to thank all KROK Investigators for providing data for this analysis. The authors also wish to thank Jolanta Cieśla for editorial help in preparing the manuscript and Patryk Korecki for statistical support.

KROK Investigators: Lech Anisimowicz, Andrzej Biederman, Dariusz Borkowski, Mirosław Brykczyński, Paweł Bugajski, Paweł Cholewiński, Romuald Cichoń, Marek Cisowski, Marek Deja, Antoni Dziatkowiak, Leszek A. Gryszko, Tadeusz Gburek, Ireneusz Haponiuk, Piotr Hendzel, Tomasz Hirnle, Stanisław Jabłonka, Krzysztof Jarmoszewicz, Marek Jasiński, Ryszard Jaszewski, Marek Jemielity, Ryszard Kalawski, Bogusław Kapelak, Jacek Kaperczak, Maciej A.Karolczak, Michał Krejca, Wojciech Kustrzycki, Mariusz Kuśmierczyk, Paweł Kwinecki, Bohdan Maruszewski, Maurycy Missima, Jacek J. Moll, Wojciech Ogorzeja, Jacek Pająk, Wojciech Pawliszak, Edward Pietrzyk, Grzegorz Religa, Jan Rogowski, Jacek Różański, Jerzy Sadowski, Girish Sharma, Janusz Skalski, Jacek Skiba, Janusz Stążka, Piotr Stępiński, Kazimierz Suwalski, Piotr Suwalski, Zdzisław Tobota, Łukasz Tułecki, Kazimierz Widenka, Michał Wojtalik, Stanisław Woś, Marian Zembala and Piotr Żelazny.

List of abbreviations

CABG

coronary artery bypass grafting

KROK

Polish National Registry of Cardiac Surgical Operations

MIDCAB

Minimally Invasive Direct Coronary Artery Bypass

OPCAB

Off-pump coronary artery bypass

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The authors received no specific funding for this work.

References

  • 1.Houlind K, Kjeldsen BJ, Madsen SN, Rasmussen BS, Holme SJ, Nielsen PH, et al. , DOORS Study Group. On-pump versus off-pump coronary artery bypass surgery in elderly patients: results from the Danish on-pump versus off-pump randomization study. Circulation 2012;125: 2431–2439. [DOI] [PubMed] [Google Scholar]
  • 2.Houlind K, Kjeldsen BJ, Madsen SN, Rasmussen BS, Holme SJ, Schmidt TA, et al. The impact of avoiding cardiopulmonary by-pass during coronary artery bypass surgery in elderly patients: the Danish On-pump Off-pump Randomisation Study (DOORS). Trials 2009;10: 47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Fronczek J, Polok KJ, Nowak-Kózka I, Włudarczyk A, Górka J, Czuczwar M, et al. Frailty is associated with an increased mortality among patients ≥ 80 years old treated in Polish ICUs Anaesthesiol Intensive Ther 2018;50: 245–251. [DOI] [PubMed] [Google Scholar]
  • 4.Gaudino M, Angelini GD, Antoniades C, Bakaeen F, Benedetto U, Calafiore AM, et al. Off-Pump Coronary Artery Bypass Grafting: 30 Years of Debate. J Am Heart Assoc 2018;7(16): e009934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Diegeler A, Börgermann J, Kappert U, Breuer M, Böning A, Ursulescu A, et al. Off-pump versus on-pump coronary-artery bypass grafting in elderly patients. N Engl J Med 2013;368(13): 1189–1198. [DOI] [PubMed] [Google Scholar]
  • 6.Nagpal AD, Bhatnagar G, Cutrara CA, Ahmed SM, McKenzie N, Quantz M, et al. Early outcomes of coronary artery bypass with and without cardiopulmonary bypass in octogenarians. Can J Cardiol 2006;22: 849–853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Suarez-Pierre A, Crawford TC, Fraser CD 3rd, Zhou X, Lui C, Taylor B, et al. Off-pump coronary artery bypass in octogenarians: results of a statewide, matched comparison. Gen Thorac Cardiovasc Surg 2019;67: 355–362. [DOI] [PubMed] [Google Scholar]
  • 8.Kuss O, von Salviati B, Borgermann J. Off-pump versus on-pump coronary artery bypass grafting: A systematic review and meta-analysis of propensity score analyses J Thorac Cardiovasc Surg 2010;140: 829–835. [DOI] [PubMed] [Google Scholar]
  • 9.Khan H, Uzzaman M, Benedetto U, Butt S, Raja SG. On- or off-pump coronary artery bypass grafting for octogenarians: A meta-analysis of comparative studies involving 27,623 patients. Int J Surg 2017;47: 42–51. [DOI] [PubMed] [Google Scholar]
  • 10.Houlind K, Fenger-Grøn M, Holme SJ, Kjeldsen BJ, Madsen SN, Rasmussen BS, et al. Graft patency after off-pump coronary artery bypass surgery is inferior even with identical heparinization protocols: results from the Danish On-pump Versus Off-pump Randomization Study (DOORS). J Thorac Cardiovasc Surg 2014;148(5): 1812–1819. [DOI] [PubMed] [Google Scholar]
  • 11.Diegeler A, Börgermann J, Kappert U, Hilker M, Doenst T, Böning A, et al. Five-Year Outcome After Off-Pump or On-Pump Coronary Artery Bypass Grafting in Elderly Patients. Circulation 2019;139: 1865–1871. [DOI] [PubMed] [Google Scholar]
  • 12.Altarabsheh SE, Deo SV, Rababa'h AM, Lim JY, Cho YH, Sharma V, et al. Off-pump coronary artery bypass reduces early stroke in octogenarians: a meta-analysis of 18,000 patients. Ann Thorac Surg 2015;99: 1568–1575. [DOI] [PubMed] [Google Scholar]
  • 13.Knapik P, Knapik M, Zembala MO, Przybyłowski P, Nadziakiewicz P, Hrapkowicz T, et al. In-hospital and mid-term outcomes in patients reoperated on due to bleeding following coronary artery surgery (from the KROK Registry). Interact Cardiovasc Thorac Surg 2019. April 9 [E-pub ahead of print]; 10.1093/icvts/ivz089 [DOI] [PubMed] [Google Scholar]
  • 14.Wu YX, Takkenberg JM, Grunkemeier GL. Measuring Follow-Up Completeness. Ann Thorac Surg 2008;85: 1155–1157 [DOI] [PubMed] [Google Scholar]
  • 15.Hulde N, Zittermann A, Deutsch MA, von Dossow V, Gummert JF, Koster A. Tranexamic acid and convulsive seizures after isolated coronary artery bypass surgery: the role of cardiopulmonary bypass and renal function. Interact Cardiovasc Thorac Surg. 2020;30: 538–540. [DOI] [PubMed] [Google Scholar]
  • 16.Benedetto U, Angelini GD, Caputo M, Feldman DN, Kim LK, Lau C, et al. Off- vs. on-pump coronary artery bypass graft surgery on hospital outcomes in 134,117 octogenarians. J Thorac Dis 2017;9(12): 5085–5092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Chikwe J, Lee T, Itagaki S, Adams DH, Egorova N. Long-Term Outcomes After Off-Pump Versus On-Pump Coronary Artery Bypass Grafting by Experienced Surgeons. J Am Coll Cardiol. 2018;72: 1478–1486. [DOI] [PubMed] [Google Scholar]
  • 18.Pawlaczyk R, Swietlik D, Lango R, Rogowski J. Off-pump coronary surgery may reduce stroke, respiratory failure, and mortality in octogenarians. Ann Thorac Surg 2012;94: 29–37. [DOI] [PubMed] [Google Scholar]
  • 19.Cavallaro P, Itagaki S, Seigerman M, Chikwe J. Operative mortality and stroke after on-pump vs off-pump surgery in high-risk patients: an analysis of 83,914 coronary bypass operations. Eur J Cardiothorac Surg 2014;45: 159–164. [DOI] [PubMed] [Google Scholar]
  • 20.LaPar DJ, Bhamidipati CM, Reece TB, Cleveland JC, Kron IL, Ailawadi G. Is off-pump coronary artery bypass grafting superior. J Thorac Cardiovasc Surg 2011;141:81–90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Gutacker N, Bloor K, Cookson R, Garcia-Armesto S, Bernal-Delgado E. Comparing hospital performance within and across countries: an illustrative study of coronary artery bypass graft surgery in England and Spain. Eur J Public Health 2015;25 Suppl 1:28–34. [DOI] [PubMed] [Google Scholar]
  • 22.Hueb W, Rezende PC, Gersh BJ, Soares PR, Favarato D, Lima EG, et al. Ten-Year Follow-Up of Off-Pump and On-Pump Multivessel Coronary Artery Bypass Grafting: MASS III. Angiology 2019;70:337–344. [DOI] [PubMed] [Google Scholar]
  • 23.Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, Srivali N, O'Corragain OA, Edmonds PJ, et al. Comparison of renal outcomes in off-pump versus on-pump coronary artery bypass grafting: A systematic review and meta-analysis of randomized controlled trials. Nephrology (Carlton). 2015;20:727–735. [DOI] [PubMed] [Google Scholar]
  • 24.Shroyer AL, Hattler B, Wagner TH, Collins JF, Baltz JH, Quin JA, et al. Five-Year Outcomes after On-Pump and Off-Pump Coronary-Artery Bypass. N Engl J Med 2017;377:623–632. [DOI] [PubMed] [Google Scholar]
  • 25.Lamy A, Devereaux PJ, Prabhakaran D, Taggart DP, Hu S, Straka Z, et al. Five-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting. N Engl J Med 2016;375:2359–2368. [DOI] [PubMed] [Google Scholar]
  • 26.Ding W, Ji Q, Wei Q, Shi Y, Ma R, Wang C. Prophylactic application of an intra-aortic balloon pump in high-risk patients undergoing off-pump coronary artery bypass grafting. Cardiology 2015;131:109–115. [DOI] [PubMed] [Google Scholar]
  • 27.Deppe AC, Weber C, Liakopoulos OJ, Zeriouh M, Slottosch I, Scherner M, et al. Preoperative intra-aortic balloon pump use in high-risk patients prior to coronary artery bypass graft surgery decreases the risk for morbidity and mortality-A meta-analysis of 9,212 patients. J Card Surg 2017;32:177–185. [DOI] [PubMed] [Google Scholar]
  • 28.Kowalczuk-Wieteska A, Parys M, Pawlaczyk R, Filipiak K, Cisowski M, Bochenek A, et al. Prediction of complications and death in octogenarians with left main coronary artery disease after coronary artery bypass implantation—off-pump, on-pump and minimally invasive techniques comparison. Postepy Kardiol Interwencyjnej 2019;15:218–225. [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Mariusz Kowalewski

27 May 2020

PONE-D-20-11113

Off-pump versus on-pump coronary artery surgery in octogenarians (from the KROK Registry)

PLOS ONE

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4. We note that there are several previous publications that analyse KROK registry data to draw conclusions about patient outcomes after coronary artery surgery; however, not all of these publications are cited and discussed in the current submission. In your revision, please ensure that all relevant preceding studies are discussed to provide appropriate context for this work, and provide details as to how the current manuscript advances on previous work.

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Reviewer #1: The authors compared On-pump vs. off Pump CABG in octgenarians of the Polish cardiac suregery registry. They found that on-Pump was associated with more perioperative complications and mortality but similar long term outcomes.

Comments

This is a well written manuscript, which is easy to comprehend. It addresses a classic but still relevant topic in cardiac surgery, i.e. the comparison of off-pump vs. on-pump bypass surgery. The data are valuable and important. However, the issue of conversions from off-pump to on-pump is not addressed. if this major confounder can be excluded, there remain only minor concerns.

Specific comments

1. One pf the big problems in the comparison of Off-Pump to On Pump is the method of data comparison. In randommized trials with an intention to treat analysis, differences are often not visible, while in retrospective analyses, conversnions from Off- to On-Pump may affect the results. It is not clear in this dataset, how this confounder was handeled. Does the database record conversions? Were they excluded? How many were there? Is the higher mortality in th on-Pump group possibly due to those converted patients ? This needs to be clarified and discussed in detail.

2. The authors state, that it is more difficult to decide for surgery in the elderly today than it was previously. The argument is not convincing, when life expectancy is increaseing. Their figures even illustrate average life expectancy of this patient population in Poland which can easily be used to make recomendations for the only treatment of coronary artery disease with a prognostic impact demonstrated in prospective randomimzed trials.

Reviewer #2: The present study investigated the effect of off-pump versus on-pump isolated CABG surgery on short-term and long-term clinical outcome in the entire cohort of Polish octogenarians who underwent cardiac surgery between 2006 and 2017. It is concluded that the off-pump technique is associated with lower in-hospital mortality than the on-pump technique, whereas long-term mortality is similar between study groups.

General comments

This is a large register analysis of Polish octogenarians. Since there is still a controversial debate regarding long-term clinical outcomes in patients undergoing off-pump or on-pump isolated CABG surgery, data are timely. However, there are issues that have to be addressed:

• Statistical analysis of unadjusted data is subject to unexplained confounding. Therefore, comparison of unadjusted data regarding clinical outcomes are irrelevant. Of scientific interest regarding the effect of off-pump versus on-pump on clinical outcome are only the PS-matched data of the manuscript. Therefore, they should primarily present the PS-matched data both in the Results section as well as in the Discussion section. The manuscript should be revised accordingly. The entire study cohort can be used, however, to perform sensitivity analyses by presenting multivariable-adjusted data (see Puehler et al. Thorac Cardiovasc Surg. 2019 Feb 9. doi: 10.1055/s-0039-1677835. [Epub ahead of print].

• In the Methods section, they should clearly define primary and secondary endpoints. This is necessary because otherwise statistical methods are needed to consider the problem of multiple testing.

• The method of PS-matching should be clearly described in the Statistics section. Moreover, the baseline characteristics used for PS-matching should be listed. Usually, standardized differences rather than p-values are used to compare baseline parameters between the two groups of the entire study cohort and the PS-matched groups. They should revise Table 1 accordingly.

• Clinical outcomes may be influenced by year of surgery, surgeon’s experience, and number of diseased vessels. It is important to consider these parameters in the PS-matched cohort. If some of these data are not available, this should be mentioned as limitation in the Discussion section.

• Several perioperative data, which may substantially influence long-term clinical outcome, are missing and should be presented by study group. These parameters include the revascularization ratio, the percentage of complete arterial revascularizations, and the ratio of posterior to inferior anastomoses.

• Although not restricted to octogenarians, they should refer to two PS-matched large studies: One study supports the early results of the present study regarding beneficial effects in the off-pump versus the on-pump group on clinical outcome (Hulde et al. Interact Cardiovasc Thorac Surg. 2020;30:538-540. The other large study, a US register analysis, reported higher mortality over 10-years of follow-up in the off-pump versus on-pump group (Chikwe et al. J Am Coll Cardiol. 2018;72:1478-1486.). Potential causes of the inconsistent results between the present data and the US data should be discussed more deeply.

Specific comments

• A flowchart of included and excluded patients should be presented.

• Completeness of follow-data should be calculated and presented in the manuscript (see Wu et al. Ann Thorac Surg 2008;85:1155-7).

• Change the titles of figures 3a+3b into ‘Probability of Survival’.

• Since they used the term ‘OPCAB’, they should also use the term ‘ONCAB’ instead of ‘CABG’ throughout the manuscript.

Reviewer #3: This is a retrospective review by Knapik and colleagues of isolated on- and off-pump CABG in octogenarians in Poland as obtained from the Polish National Registry of Cardiac Surgical Procedures (KROK). The primary aims of the study were to evaluate 1. perioperative (in -hospital mortality and complications) and 2. long term outcomes (all cause mortality).

Major Comments:

1. Why use the date of discharge as the starting point for survival; this is a somewhat odd choice? Isn't the day of operation more standard and more representative of survival from an operation? Were perioperative in-hospital deaths eliminated from the survival curves by using the day of discharge as the starting point? what is a patient was discharged 3 months after the operation, the day after discharge is survival day #1?

2. A statement that informed consent was waived by whatever appropriate review board should be included in the paper (if not obtained then rationale for why not should be included but hard to justify)

3. On line 165, you report the mean age was only 82 which means that the vast majority of patients with <85 years old. In Table 1, you report only 39 patients were over 90; can you include additional information about the number of patients over 85 and less than 90? This will help surgeons when applying data to their practices about what "octogenarians" you are operating on.

4. Can you provide any information as to surgeon performance of both procedures? For instance, did surgeons performing OPCAB represent only a small percentage of total surgeons performing most of the operations or were OPCAB's performed by a wide variety of surgeons in a small percentage of patients? It would be important to know if the outcomes could be generalized to essentially any surgeon even if less experienced. Near the end of the discussion, you mention that surgeons' rationale for procedure selection is unknown and also there were centers where OPCAB was widely used (and presumably some where it was rarely used) Can you provide any information as to variation by institution? by surgeon?

5. Although a Kaplan Meier curve can be used to depict the time on ventilator following surgery, the inclusion of 2 figures just to show this before and after propensity matching seems excessive; please remove and instead pick one or two additional individual time points to demonstrate the difference (you talk about the 24 hr time point already in the text). Also, please comment on the "significance" of the difference (13.0% versus 8.2% after 24 hrs); was there higher ventilator associated pneumonias in the patients remaining ventilated. Was there still a significant difference after 48 hrs? What about after 3 or more days?

6. The statement on lines 353-355 "This is a situation when locally obtained, retrospective data should be treated with the same attention as the results of a perfectly designed prospective, randomized trials." is not consistent with known biases that occur with patient selection in retrospective trials which cannot be consistently corrected with "propensity matching" This comment should be removed as "perfectly planned prospective randomized trials remain the gold standard.

7. Your conclusion paragraph states a little too strongly that OPCAB should be the method of choice in octogenarians and this statement and the data may not apply to certain subsets of patient where on pump CABG would be a better choice. This statement should be softened to something like "suggest that the OPCAB technique should be considered as perfectly acceptable in octogenarians when performed by surgeons experienced in the technique."

Minor Comments:

1. Table 2 title: please correct spelling of "patiets" to patients

2. On lines 223-24 the statement ""the incidence of the some postoperative complications was still higher in the on-pump group." does not make sense; please correct

Reviewer #4: PONE-D-20-11113: statistical review

SUMMARY. This is a retrospective study that investigates in-hospital and long-term mortality among octogenarians undergoing off-pump and on-pump coronary artery bypass surgery. The core statistical analysis is based on the comparison of survival curves under off-pump or on-pomp treatments. Although the results seem sound and the material is well organized, the paper lacks details (major issue 1) and the data are not provided (major issue 2). These issues complicate not only the interpretation of the results but also their reproducibility. I also list a couple of specific points that should be addressed.

MAJOR ISSUES

1. Propensity score matching. The paper does not provide enough details about the methods used, making it impossible to reproduce the results. Please provide these details and especially clarify (1) whether you used a logistic regression model to estimate the propensity score (in this case, please provide the estimates, perhaps as supplementary material) and (2) the covariates that have been used (did you consider any variable selection method?).

2. Data availability. Although the authors declare that the data are available without restrictions and that they are within the manuscript and its Supporting Information files, data are not attached. Data should be provided as a supplementary information file along with the metadata needed to process the file.

SPECIFIC POINTS

1. Line 152 “Multivariate analysis of long-term results was performed with the use of the Cox-proportional hazard model.” I can’t see the results of this analysis in the paper. Please clarify.

2. Line 150 “These data were then analyzed using the Kaplan-Meier method with log-rank testing.”. What kind of log-rank test? While the standard log-rank test is frequently used for testing the equality of survival curves in propensity score matched samples, such an approach is inappropriate, because it requires that the samples be independent of one another. Instead, the stratified log-rank test can be used to compare the equality of the survival curves in matched samples.

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PLoS One. 2020 Sep 10;15(9):e0238880. doi: 10.1371/journal.pone.0238880.r002

Author response to Decision Letter 0

10 Jul 2020

Reviewer #1:

The authors compared On-pump vs. off Pump CABG in octgenarians of the Polish cardiac surgery registry. They found that on-Pump was associated with more perioperative complications and mortality but similar long term outcomes.

Comments

This is a well written manuscript, which is easy to comprehend. It addresses a classic but still relevant topic in cardiac surgery, i.e. the comparison of off-pump vs. on-pump bypass surgery. The data are valuable and important. However, the issue of conversions from off-pump to on-pump is not addressed. if this major confounder can be excluded, there remain only minor concerns.

Specific comments

1. One of the big problems in the comparison of Off-Pump to On Pump is the method of data comparison. In randomized trials with an intention to treat analysis, differences are often not visible, while in retrospective analyses, conversnions from Off- to On-Pump may affect the results. It is not clear in this dataset, how this confounder was handeled. Does the database record conversions? Were they excluded? How many were there? Is the higher mortality in th on-Pump group possibly due to those converted patients ? This needs to be clarified and discussed in detail.

Answer:

There is a field for conversions in the KROK database. Overall, 53 conversions were identified among 6,006 patients (0.9%), however the type of surgical procedure was marked differently in these patients. For patients with conversion, users of the KROK database chose either the finally performed surgical procedure (CABG) or the originally planned surgical procedure (OPCAB). To avoid any doubt with the grouping variable (OPCAB/CABG), all these patients now have been excluded. The number of patients was therefore reduced, and their total number was reduced from 6,006 to 5,953 patients. The percentage of in-hospital mortality in a subgroup of 53 patients with conversion was 32%.

Action:

All patients with conversion have been excluded. All calculations have therefore been repeated, with appropriate changes in the text and all tables. An explanation of the reason for exclusion of patients with conversion has been added to the Methods section.

2. The authors state, that it is more difficult to decide for surgery in the elderly today than it was previously. The argument is not convincing, when life expectancy is increaseing. Their figures even illustrate average life expectancy of this patient population in Poland which can easily be used to make recomendations for the only treatment of coronary artery disease with a prognostic impact demonstrated in prospective randomimzed trials.

Answer:

We are in agreement with this comment.

Action:

This sentence has been deleted from the text.

Reviewer #2:

The present study investigated the effect of off-pump versus on-pump isolated CABG surgery on short-term and long-term clinical outcome in the entire cohort of Polish octogenarians who underwent cardiac surgery between 2006 and 2017. It is concluded that the off-pump technique is associated with lower in-hospital mortality than the on-pump technique, whereas long-term mortality is similar between study groups.

General comments:

This is a large register analysis of Polish octogenarians. Since there is still a controversial debate regarding long-term clinical outcomes in patients undergoing off-pump or on-pump isolated CABG surgery, data are timely. However, there are issues that have to be addressed:

Statistical analysis of unadjusted data is subject to unexplained confounding. Therefore, comparison of unadjusted data regarding clinical outcomes are irrelevant. Of scientific interest regarding the effect of off-pump versus on-pump on clinical outcome are only the PS-matched data of the manuscript. Therefore, they should primarily present the PS-matched data both in the Results section as well as in the Discussion section. The manuscript should be revised accordingly. The entire study cohort can be used, however, to perform sensitivity analyses by presenting multivariable-adjusted data (see Puehler et al. Thorac Cardiovasc Surg. 2019 Feb 9. doi: 10.1055/s-0039-1677835. [Epub ahead of print].

Answer:

We fully agree, that only PS-matched data are relevant to draw conclusions from, thus our results and conclusions are based only on PS-matched data. The same is also true for the Discussion section, where we again, discuss only PS-matched data.

We somewhat disagree however, that we do not need to provide unadjusted data at all. To the best of our knowledge, the authors should provide both unadjusted and PS-matched data, hence our provision of both dataset in the tables.

Following a discussion with our statistician, we came to the conclusion that there was no need to perform sensitivity analysis by presenting multivariable-adjusted data.

Action:

None

In the Methods section, they should clearly define primary and secondary endpoints. This is necessary because otherwise statistical methods are needed to consider the problem of multiple testing.

Answer:

In the Methods section of our study we stated the following: „The primary outcomes of this study were the in-hospital mortality rate and the incidence of perioperative complications. The secondary outcome was all-cause mortality in a long-term follow-up period.” Therefore, both the primary and secondary endpoints were clearly defined in the Methods section. The only difference was in using the word “outcome” instead of “endpoint”. We are happy to change this as per the reviewer’s suggestion.

Action:

None

The method of PS-matching should be clearly described in the Statistics section. Moreover, the baseline characteristics used for PS-matching should be listed. Usually, standardized differences rather than p-values are used to compare baseline parameters between the two groups of the entire study cohort and the PS-matched groups. They should revise Table 1 accordingly.

Answer:

Patients for comparison were matched to achieve the similar pre-operative status. The data was matched with the Greedy data matching algorithm using Mahalanobis distance within propensity score calipers. Each caliper radius was set to 0.2*Sigma. Propensity score was calculated using logistic regression. We used all variables from Table 1.

To assess the covariate balance, z-difference coefficients were calculated for each variable before and after matching. The mean value before and after the match was 0.28 and -0.30, respectively, and the variances were 79.31 and 0.32, respectively. Attached are detailed data about PSM.

We added the appropriate description in the Methods section and therefore, the method of PS-matching is clearly described.

Additionally, we fully agree with the Reviewer that standardized differences should be also used to compare baseline parameters between the two groups of the entire study cohort and the PS-matched groups. We have therefore expanded and revised Table 1 accordingly.

Action:

The method of PS-matching has been clearly described in the Methods section. To attain this goal, we added the appropriate description in the Methods section.

We have also expanded Table 1 (adding two additional columns) to present standardized differences to compare baseline parameters between the two groups of the entire study cohort and the PS-matched groups.

Clinical outcomes may be influenced by year of surgery, surgeon’s experience, and number of diseased vessels. It is important to consider these parameters in the PS-matched cohort. If some of these data are not available, this should be mentioned as limitation in the Discussion section.

Answer:

We fully agree that clinical outcomes may be influenced by the year of surgery. However, dividing year of surgery into 12 separate variables (describing each consecutive year) does not seem like a good approach. Instead, we divided the analyzed time period into three relatively equal time periods (2006-2009, 2010-2013, 2014-2017), adding this information to a newly created part of table 1 (entitled “year of surgery’) and adding this variable to the PS-matching.

With regards to your point about surgeon’s experience, there is unfortunately nothing we can do to improve the quality of our calculations. Part of the limitations of the KROK database is that it doesn’t provide information about the surgical experience of individual Polish cardiac surgeons. Whilst we agree that such a parameter would be very useful, we regret that it is something we cannot obtain.

Number of diseased vessels does not exist in a KROK database as a separate variable, however, we have information available on the number of grafts. Therefore, we divided the amount of grafts performed per patient into three categories: “1 graft”, “2 grafts” and “3 or more grafts”. Three additional rows have been therefore added to “procedure related variables” in the table and these variables were also added to the PS-matching.

Action:

We divided the analyzed time period into three relatively equal time periods (2006-2009, 2010-2013, 2014-2017), adding this information to a newly created part of table 1 (entitled “year of surgery”) and adding this variable to the PS-matching. Also, we divided the amount of grafts performed per patient into three categories: “1 graft”, “2 grafts”, “3 or more grafts”. Additional rows have been therefore added to “procedure related variables” in table 1 and these variables were also added to the PS-matching.

Several perioperative data, which may substantially influence long-term clinical outcome, are missing and should be presented by study group. These parameters include the revascularization ratio, the percentage of complete arterial revascularizations, and the ratio of posterior to inferior anastomoses.

Answer:

Unfortunately, variables such as revascularization ratio and the ratio of posterior to inferior anasomoses are not available in the KROK Registry. We were able however, to identify, which patients underwent a complete arterial revascularization. Therefore, this variable was also added to table 1 (as another „procedure-related variable”) and was included in a PS-matching.

Action:

Variable “complete arterial revascularization” was also added to table 1 (among “procedure-related variables”) and was also included in a PS-matching.

Although not restricted to octogenarians, they should refer to two PS-matched large studies: One study supports the early results of the present study regarding beneficial effects in the off-pump versus the on-pump group on clinical outcome (Hulde et al. Interact Cardiovasc Thorac Surg. 2020;30:538-540. The other large study, a US register analysis, reported higher mortality over 10-years of follow-up in the off-pump versus on-pump group (Chikwe et al. J Am Coll Cardiol. 2018;72:1478-1486.). Potential causes of the inconsistent results between the present data and the US data should be discussed more deeply.

Answer:

It has been done, according to the Reviewers’ suggestion.

Action:

Two consecutive paragraphs in the Discussion section have been extended to include this comment and the above mentioned two references have been added to the list of references. Additional sentences are added at the end of each paragraph.These paragraphs are now as follows:

“Our findings suggest that octogenarians constitute a high-risk population and the off-pump procedure appears superior among patients scheduled for isolated coronary artery bypass surgery for these patients in terms of in-hospital results. Utilization of the on-pump technique resulted in significantly higher in-hospital mortality (8.4% vs 4.7%, p<0.001) and similar all-cause mortality in the long-term follow-up period in survivors (p=0.362). The increased in-hospital mortality was likely due to the higher incidence of postoperative complications (mainly reoperation due to bleeding) in the on-pump group. Similar conclusions were drawn by Hulde et al. who observed that the duration of mechanical ventilation duration, intensive care unit stay, the risk of stroke, in-hospital mortality and 30-day mortality were significantly lower in the off-pump group than in the on-pump group (Hulde et al. Interact Cardiovasc Thorac Surg. 2020;30:538-540).

Comparative findings reported in the literature are contradictory. One recent retrospective study, analyzing 134.117 discharge records from 797 US hospitals, found that in-hospital mortality did not differ between octogenarians who underwent CABG and OPCAB (5.5% vs. 5.2%, p=0.3) [14]. At the same time, a recent systematic review based on 16 retrospective studies (performed in 27.623 octogenarians overall) found that the OPCAB technique was associated with significantly lower in-hospital mortality [9]. The other large study, a US register analysis by Chikwe et al., reported higher mortality over 10-years of follow-up in the off-pump versus on-pump group (Chikwe et al. J Am Coll Cardiol. 2018;72:1478-1486.)”.

Specific comments

A flowchart of included and excluded patients should be presented.

Answer:

It has been done.

Action:

A flowchart has been added in a form of Figure 1. The numbers of the remaining figures have been changed accordingly.

Completeness of follow-data should be calculated and presented in the manuscript (see Wu et al. Ann Thorac Surg 2008;85:1155-7).

Answer:

Completness of follow-up data have been calculated according to the method described by Wu et. al. We described the method of this assessment in the Methods section (adding an additional reference) and presented the results on the beginning of the Results section.

Additionally, we have noticed that we have specified a wrong closing date regarding the follow-up assessment. It has been now corrected in the text of the Methods section.

Action:

In the Methods section we added the following sentence:

„Completness of follow-up data was calculated according to the method described by Wu et. al. [appropriate reference number will be cited here]”.

In the Results section we added the following sentence:

„Completness of follow-up data according to Clark’s C-index was 78.6% and the modified C*-index was 88.8%.”

Also, in the Methods section we have changed the following sentence:

“Assessment of long-term follow-up data included analysis of all-cause mortality. The National Health Fund death database was searched for all patients included in this study from the date of their procedure until 31st of March 2016”.

to:

“Assessment of long-term follow-up data included analysis of all-cause mortality. The National Health Fund death database was searched for all patients included in this study from the date of their procedure until 30the of September 2017”.

Change the titles of figures 3a+3b into ‘Probability of Survival’.

Answer:

It has been done.

Action:

Titles of Figures 3a and 3b have been changed in a figure legend and above the figures, according to the Reviewers’ suggestion.

Since they used the term ‘OPCAB’, they should also use the term ‘ONCAB’ instead of ‘CABG’ throughout the manuscript.

Answer:

We used the term “CABG” for on-pump coronary artery surgery, because this term is used by the Committee of the European Association for Cardio-Thoracic Surgery( EACTS) in the most recent Clinical Guidelines on Myocardial Revascularization from 2018. In these guidelines, the term CABG (not ONCAB) is used. We may change it, but we would be grateful if you could consider our point of view.

Action:

None.

Reviewer #3:

This is a retrospective review by Knapik and colleagues of isolated on- and off-pump CABG in octogenarians in Poland as obtained from the Polish National Registry of Cardiac Surgical Procedures (KROK). The primary aims of the study were to evaluate 1. perioperative (in -hospital mortality and complications) and 2. long term outcomes (all cause mortality).

Major Comments:

1. Why use the date of discharge as the starting point for survival; this is a somewhat odd choice? Isn't the day of operation more standard and more representative of survival from an operation? Were perioperative in-hospital deaths eliminated from the survival curves by using the day of discharge as the starting point? what is a patient was discharged 3 months after the operation, the day after discharge is survival day #1?

Answer:

Using the date of discharge as a starting point was intentional but we fully acknowledge the Reviewer’s point, especially with regard to the following comment “Perioperative in-hospital deaths were eliminated from the survival curves by using the day of discharge as the starting point”.

We feel that using the day of operation as a starting point might create a lot of bias in this particular group. In case of significant in-hospital mortality and relatively frequent postoperative complications (among our octogenarians undergoing CABG), this would create an influence of in-hospital mortality on long-term results. The survival curves would in this case, separate at the beginning and then remain parallel during the whole postoperative course (even when in fact there was no difference in the long-term results). There are examples in the medical literature, where such an approach led to drawing wrong conclusions (see Masyuk et al. Intensive Care Med. 2019;45:55 and our commentary in Knapik et al. Intensive Care Med. 2019 Aug;45:1172.)

If we adopted the strategy proposed by the Reviewer, we would probably have significantly worse long-term results in the CABG group, because in-hospital mortality in this group was much higher and the curve would start on the day of surgery. We are therefore convinced that choosing the day of operation as a starting point should not be considered as a gold standard in all surgical procedures. Furthermore, we would like to mention that the same solution (taking the date of discharge as a starting point) has been previously successfully used – for the same reason – in our paper published in the Interactive Cardiovascular and Thoracic Surgery in 2019, when we analyzed reoperations due to postoperative bleeding on a basis of data from the KROK Registry (Knapik et al. Interact Cardiovasc Thorac Surg. 2019 Apr 9;ivz089. doi: 10.1093/icvts/ivz089).

Action:

None

2. A statement that informed consent was waived by whatever appropriate review board should be included in the paper (if not obtained then rationale for why not should be included but hard to justify)

Answer:

Informed consent was waived by our Ethical Committee.

Action:

The following sentence has been added to the Methods section: “Due to the retrospective and anonymous nature of the study, Ethical Committee of the Medical University of Silesia in Katowice waived the need for consent of the patients to participate in the study.”

3. On line 165, you report the mean age was only 82 which means that the vast majority of patients with <85 years old. In Table 1, you report only 39 patients were over 90; can you include additional information about the number of patients over 85 and less than 90? This will help surgeons when applying data to their practices about what "octogenarians" you are operating on.

Answer:

An additional age category of patient between 86 – 90 years has been additionally specified as a separate variable.

Action:

Table 1 has been revised accordingly. This variable has been also added to PS-matching.

4. Can you provide any information as to surgeon performance of both procedures? For instance, did surgeons performing OPCAB represent only a small percentage of total surgeons performing most of the operations or were OPCAB's performed by a wide variety of surgeons in a small percentage of patients? It would be important to know if the outcomes could be generalized to essentially any surgeon even if less experienced. Near the end of the discussion, you mention that surgeons' rationale for procedure selection is unknown and also there were centers where OPCAB was widely used (and presumably some where it was rarely used) Can you provide any information as to variation by institution? by surgeon?

Answer:

Based on the data from the KROK registry, we are unable to determine the degree of experience of cardiac surgeons in performing various types of coronary procedures. One could probably get information on what percentage of off-pump coronary surgery was performed in the individual centers and, accordingly, carry out appropriate PS-matching, but this might be also prone to serious bias. For example, there might be centers that used to carry out only few off-pump procedures in the past, where the surgical team was suddenly joined by one or two surgeons skilled in off-pump surgery. The same mechanism may also work the other way. The results may rapidly change in both cases and thus, such analysis does not seem logical.

Action:

None

5. Although a Kaplan Meier curve can be used to depict the time on ventilator following surgery, the inclusion of 2 figures just to show this before and after propensity matching seems excessive; please remove and instead pick one or two additional individual time points to demonstrate the difference (you talk about the 24 hr time point already in the text). Also, please comment on the "significance" of the difference (13.0% versus 8.2% after 24 hrs); was there higher ventilator associated pneumonias in the patients remaining ventilated. Was there still a significant difference after 48 hrs? What about after 3 or more days?

Answer:

It is true that having two curves showing ventilation time (before and after PS-matching) is indeed excessive. Therefore, one curve (showing ventilation times before PS-matching) has been removed.

It was also suggested that we pick one or two individual time points to demonstrate the difference. Our issue with that is that in our opinion, analysis of the duration of postoperative ventilation makes more sense in the first 24 hours after surgery, for example 12 hours after the end of the procedure. This moment however, is clearly seen on the existing curves.

In our view, a higher percentage of patients still being ventilated in the following days would have a relationship primarily with postoperative complications. Also, patients who die in the postoperative period may have had relatively short ventilation times. Therefore, we decided not to analyze a more distant postoperative period in terms of postoperative ventilation

Action:

One curve (showing ventilation times before PS-matching) was removed.

6. The statement on lines 353-355 "This is a situation when locally obtained, retrospective data should be treated with the same attention as the results of a perfectly designed prospective, randomized trials." is not consistent with known biases that occur with patient selection in retrospective trials which cannot be consistently corrected with "propensity matching" This comment should be removed as "perfectly planned prospective randomized trials remain the gold standard.

Answer:

It is true that perfectly planned prospective randomized trials remain a gold standard. We have therefore decided to change this sentence to: “Such strong scientific evidence should lead to careful evaluation of the optimal method of revascularization in this group of patients in Poland. This is also a situation when locally obtained, retrospective data should be taken seriously.”

Action:

The following piece of text has been modified in the Discussion section: „Such strong scientific evidence should lead to careful evaluation of the optimal method of revascularization in this group of patients in Poland. This is also a situation when locally obtained, retrospective data are of great practical importance.”

7. Your conclusion paragraph states a little too strongly that OPCAB should be the method of choice in octogenarians and this statement and the data may not apply to certain subsets of patient where on pump CABG would be a better choice. This statement should be softened to something like "suggest that the OPCAB technique should be considered as perfectly acceptable in octogenarians when performed by surgeons experienced in the technique."

Answer:

We fully agree that our conclusion strongly states that OPCAB should be the method of choice in octogenarians. Therefore, we have decided to change the conclusion according to the Reviewer’s suggestion.

Action:

At the end of the Discussion section, the following sentence replaced the previous statement: “Based on the results of this study, we suggest that the OPCAB technique should be considered as perfectly acceptable in octogenarians when performed by surgeons experienced in the technique”.

Also, in the conclusion of the abstract, the sentence has been changed to: “On the basis of our findings we suggest that off pump technique should be considered as perfectly acceptable in octogenarians.”

Minor Comments:

1. Table 2 title: please correct spelling of "patiets" to patients

Answer:

We agree with this comment.

Action:

It has been corrected.

2. On lines 223-24 the statement ""the incidence of the some postoperative complications was still higher in the on-pump group." does not make sense; please correct.

Answer:

We agree with this comment.

Action:

It has been corrected to: „Following propensity matching, the incidence of postoperative respiratory complications and reoperation due to bleeding was higher in the on-pump group”.

Reviewer #4: PONE-D-20-11113: statistical review

SUMMARY. This is a retrospective study that investigates in-hospital and long-term mortality among octogenarians undergoing off-pump and on-pump coronary artery bypass surgery. The core statistical analysis is based on the comparison of survival curves under off-pump or on-pomp treatments. Although the results seem sound and the material is well organized, the paper lacks details (major issue 1) and the data are not provided (major issue 2). These issues complicate not only the interpretation of the results but also their reproducibility. I also list a couple of specific points that should be addressed.

MAJOR ISSUES

1. Propensity score matching. The paper does not provide enough details about the methods used, making it impossible to reproduce the results. Please provide these details and especially clarify (1) whether you used a logistic regression model to estimate the propensity score (in this case, please provide the estimates, perhaps as supplementary material) and (2) the covariates that have been used (did you consider any variable selection method?).

Answer:

The issue regarding the details regarding propensity score matching has been already raised by Reviewer 2. We therefore added the appropriate sentences to the Methods section. The method of PS-matching is now described in detail in this chapter.

Action:

The following sentence has been added to the Methods section:

“Data were matched with the Greedy data matching procedure using Mahalanobis distance within propensity score calipers. Caliper radius were set to 0.2*Sigma. Propensity score was calculated using logistic regression. We used all variables from table 1. To assess the covariate balance, z-difference coefficients were calculated for each variable before and after matching. The mean value before and after the match was 0.28 and -0.30, respectively, and the variance was 79.31 and 0.32.”

Details regarding logistic regression model and covariates have been attached in the supplementary file 1.

2. Data availability. Although the authors declare that the data are available without restrictions and that they are within the manuscript and its Supporting Information files, data are not attached. Data should be provided as a supplementary information file along with the metadata needed to process the file.

Answer:

The Polish National Registry of Cardiac Surgical Operations (KROK Registry) operates under the supervision of the Polish Ministry of Health and the scope of data subject to public disclosure is strictly defined. Data allowed to be made publicly available have been now attached together with the description. These data enable repetition of our follow-up analysis.

Action:

Data allowed to be publicly available have been now attached together with the description as Supplementary file 2. These data enable repetition of our follow-up analysis.

SPECIFIC POINTS

1. Line 152 “Multivariate analysis of long-term results was performed with the use of the Cox-proportional hazard model.” I can’t see the results of this analysis in the paper. Please clarify.

Answer:

Multivariate analysis of long-term results was not performed with the use of Cox-proportional hazard model. This sentence was found in the text of the study by mistake. We would like to apologize for that.

Action:

The sentence „Multivariate analysis of long-term results was performed with the use of the Cox-proportional hazard model” was deleted from the text of the Methods section.

2. Line 150 “These data were then analyzed using the Kaplan-Meier method with log-rank testing.”. What kind of log-rank test? While the standard log-rank test is frequently used for testing the equality of survival curves in propensity score matched samples, such an approach is inappropriate, because it requires that the samples be independent of one another. Instead, the stratified log-rank test can be used to compare the equality of the survival curves in matched samples.

Answer:

Log-rank test which has been used is the stratified log-rank test.

Action:

The information regarding the type of log-rank test was added to the appropriate sentence in the Methods section.

Attachment

Submitted filename: recenzje Plos One_9.doc

Click here for additional data file. (60.5KB, doc)

Decision Letter 1

Mariusz Kowalewski

29 Jul 2020

PONE-D-20-11113R1

Off-pump versus on-pump coronary artery surgery in octogenarians (from the KROK Registry)

PLOS ONE

Dear Dr. Knapik,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Sep 12 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Mariusz Kowalewski

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

We are interested in publishing your manuscript; however, one reviewer continues to have significant concerns with your revised manuscript. Before the paper can be accepted in its final form we would like your comments to the critiques. Accordingly, we invite you to respond to all the reviewers' comments and recommendations. A decision on acceptability of your manuscript will be made only after the revised version has been reevaluated.

In particular, the Reviewer is concerned about exclusion of conversion cases and censoring the time-to-event analysis by the date of discharge. While removing in-hospital mortality from the analysis may better help understand the postoperative sequelae in these patients unobscured by features inherent to the in-hospital course, the principal analysis should include both in-hospital and long-term; i therefore suggest to keep censored analysis to the supplement only but cite the results in the respective paragraph, similarly for the conversion cases, please report the mortality rates for both per-protocol and ITT scenarios.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: (No Response)

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: No

Reviewer #4: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors adequately addressed all of the concerns. Nevertheless, there remains a certain risk of bias due to multiple confounders. Therefore, the authors should consider to tune down their conclusion.

Reviewer #3: 1. The elimination of the conversion patients (which should be almost all OPCAB converted to CABG since many fewer might be converted to OPCAB from CABG due to porcelain aorta, etc. I do not believe that these patients should be excluded because they have a very high mortality rate which therefore biases the results if these were intended to be OPCAB patients!

2. The authors explanation for the bias introduced by using the date of discharge as the start of survival is unsupportable. The elimination of mortality by this method cannot be avoided by surgeons and therefore to say that "if you make it to discharge" that OPCAB is more likely to survive (but the opposite is true if you take into account the mortality of conversions and perioperative deaths) is erroneous and not acceptable.

Reviewer #4: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: No

Reviewer #4: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Sep 10;15(9):e0238880. doi: 10.1371/journal.pone.0238880.r004

Author response to Decision Letter 1

24 Aug 2020

Additional Editor Comments (if provided):

We are interested in publishing your manuscript; however, one reviewer continues to have significant concerns with your revised manuscript. Before the paper can be accepted in its final form we would like your comments to the critiques. Accordingly, we invite you to respond to all the reviewers' comments and recommendations. A decision on acceptability of your manuscript will be made only after the revised version has been reevaluated.

In particular, the Reviewer is concerned about exclusion of conversion cases and censoring the time-to-event analysis by the date of discharge. While removing in-hospital mortality from the analysis may better help understand the postoperative sequelae in these patients unobscured by features inherent to the in-hospital course, the principal analysis should include both in-hospital and long-term; i therefore suggest to keep censored analysis to the supplement only but cite the results in the respective paragraph, similarly for the conversion cases, please report the mortality rates for both per-protocol and ITT scenarios.

Answer:

As previously explained, 53 conversions were identified among 6,006 patients (0.9%), however the type of surgical procedure was marked differently in these patients. For patients with conversion, users of the KROK database chose either the finally performed surgical procedure (CABG) or the originally planned surgical procedure (OPCAB). Therefore, to avoid any doubt with the grouping variable (OPCAB/CABG), we proposed to exclude these patients. The number of patients was therefore reduced, and their total number was reduced from 6,006 to 5,953 patients.

We understand however, that the Reviewer might have been concerned about exclusion of conversion cases, as the in-hospital mortality in this subgroup of 53 patients was as high as 32%. Therefore, we decided to follow the intention-to-treat approach and all patients with conversion were allocated in the OPCAB group. In the Results section however, we decided to present mortality rates for both per-protocol and ITT scenario.

Additionally, the Reviewer was also concerned about censoring the time-to-event analysis by the date of discharge, and indicated that the principal analysis should include both in-hospital and long-term results.

While we generally agree with this view, we feel that using the day of operation as a starting point might create a lot of bias in this particular situation. The reasons for that have been already explained. In case of significant in-hospital mortality and relatively frequent postoperative complications (among our octogenarians undergoing CABG), this would create an influence of in-hospital mortality on long-term results. The survival curves would in this case, separate at the beginning and then remain parallel during the whole postoperative course (even when in fact there was no difference in the long-term results). It turned out, that we were right – when the starting point of our analysis was changed, the survival curves following propensity scoring starting at the day of operation indicated that long-term survival was significantly better (p=0.013) in the OPCAB group (despite the fact that all conversions are being now analyzed in the OPCAB group).

We understand however, that the Reviewer might have been concerned with our previous approach. Therefore, we performed the principal analysis starting at the day of the operation and took Editors’ comment to keep censored analysis to the supplement only.

Action:

All patients with conversion were allocated in the OPCAB group. As a consequence, all results had to be recalculated and new data are now presented in all tables and figures, and appropriate changes were also made in the whole text of the manuscript. Additionally, in the Results section, we presented mortality rates for both per-protocol and ITT scenario, as required.

Also, we performed the principal analysis starting at the day of the operation. Additionally, we presented our censored analysis to the supplement only (as Supplementary file 3), presenting the results of this additional analysis in the Results section. On a basis of these calculations, we had to change one of the results of our study (regarding a long-term follow up).

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: (No Response)

Reviewer #4: All comments have been addressed

________________________________________

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: No

Reviewer #4: (No Response)

________________________________________

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: (No Response)

________________________________________

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: (No Response)

________________________________________

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: (No Response)

________________________________________

6. Review Comments to the Author.

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1:

The authors adequately addressed all of the concerns. Nevertheless, there remains a certain risk of bias due to multiple confounders. Therefore, the authors should consider to tune down their conclusion.

Answer:

This issue has been already raised in a previous round by another Reviewer who stated: „Your conclusion paragraph states a little too strongly that OPCAB should be the method of choice in octogenarians and this statement and the data may not apply to certain subsets of patient where on pump CABG would be a better choice. This statement should be softened…”

On a basis of this comment, we have decided to change the conclusion according to the Reviewer’s suggestion. Therefore, the conclusion has been already tuned down during a previous review round.

Action:

At the end of the Discussion section, the following sentence replaced the previous statement: “Based on the results of this study, we suggest that the OPCAB technique should be considered as perfectly acceptable in octogenarians when performed by surgeons experienced in the technique”.

Also, in the conclusion of the abstract, the sentence has been changed to: “On the basis of our findings we suggest that off pump technique should be considered as perfectly acceptable in octogenarians.”

These changes have been already done during a previous review round.

Reviewer #3:

1. The elimination of the conversion patients (which should be almost all OPCAB converted to CABG since many fewer might be converted to OPCAB from CABG due to porcelain aorta, etc. I do not believe that these patients should be excluded because they have a very high mortality rate which therefore biases the results if these were intended to be OPCAB patients!

Answer:

As explained during a previous review round, 53 conversions were identified among 6,006 patients (0.9%), however the type of surgical procedure was marked differently in these patients. For patients with conversion, users of the KROK database chose either the finally performed surgical procedure (CABG) or the originally planned surgical procedure (OPCAB). Therefore, to avoid any doubt with the grouping variable (OPCAB/CABG), we initially proposed to exclude these patients. The number of patients was therefore reduced, and their total number was reduced from 6,006 to 5,953 patients in a previous version of the manuscript.

We understand however, that exclusion of conversion cases might not be acceptable, particularly when the in-hospital mortality in this subgroup of 53 patients was as high as 32%. Therefore, we decided to follow the intention-to-treat approach and all patients with conversion were allocated in the OPCAB group. In the Results section however, we decided to present mortality rates for both per-protocol and ITT scenario, as required.

Action:

All patients with conversion were allocated in the OPCAB group. As a consequence, all results had to be recalculated and new data are now presented in all tables and figures, and appropriate changes were also made in the whole text of the manuscript. Additionally, in the Results section, we presented mortality rates for both per-protocol and ITT scenario (as proposed by the Editor).

In the Results section the following sentence was therefore added: “Conversions from OPCAB do CABG were analyzed in the OPCAB group”.

2. The authors explanation for the bias introduced by using the date of discharge as the start of survival is unsupportable. The elimination of mortality by this method cannot be avoided by surgeons and therefore to say that "if you make it to discharge" that OPCAB is more likely to survive (but the opposite is true if you take into account the mortality of conversions and perioperative deaths) is erroneous and not acceptable.

Answer:

We understand, that the Reviewer might have been concerned with our approach, when the survival curves start at the date of discharge. Therefore, we now performed the principal analysis starting at the day of the operation and took Editors’ comment to keep censored analysis to the supplement only, presenting the results of this additional analysis in the respective paragraph.

Action:

We recalculated our data and performed the principal analysis starting at the day of the operation. Additionally, we presented our censored analysis to the supplement only (adding Supplementary file 3), presenting the results of this additional analysis in the Results section. Changes were also done in the whole text of the manuscript, as appropriate.

When the starting point of our analysis was changed, the survival curves following propensity scoring starting at the day of operation indicated that long-term survival was significantly better (p=0.013) in the OPCAB group (despite the fact that all conversions are being now analyzed in the OPCAB group). Therefore, we had to do some minor changes in the text of the manuscript (in the abstract, and in the Results and Discussion section)..

Reviewer #4: (No Response)

________________________________________

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: No

Reviewer #4: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: Response to Reviewers_3.doc

Click here for additional data file. (71KB, doc)

Decision Letter 2

Mariusz Kowalewski

26 Aug 2020

Off-pump versus on-pump coronary artery surgery in octogenarians (from the KROK Registry)

PONE-D-20-11113R2

Dear Dr. Knapik,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Mariusz Kowalewski

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

No other comments from academic editor

Reviewers' comments:

Acceptance letter

Mariusz Kowalewski

28 Aug 2020

PONE-D-20-11113R2

Off-pump versus on-pump coronary artery surgery in octogenarians (from the KROK Registry)

Dear Dr. Knapik:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Mariusz Kowalewski

Academic Editor

PLOS ONE

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