Combined Antegrade–Retrograde Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting in Patients with Left Main Coronary Artery Disease: The CARDIOPROTECT-LMCAD Randomised Trial

Q: What are the key findings of this study?

Combined antegrade-retrograde blood cardioplegia did not reduce peak postoperative hs-cTnI within 48 hours compared with antegrade-only cardioplegia.

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Significant left main coronary artery disease (LMCAD) undergoing elective isolated on-pump coronary artery bypass grafting (CABG) (n=60). Intervention: Combined antegrade-retrograde blood cardioplegia vs. Antegrade-only blood cardioplegia via aortic root at 200-300 mL/min (pressure <=100 mmHg) with identical induction/maintenance dosing and terminal warm reperfusion. Primary outcome: Peak postoperative high-sensitivity cardiac troponin I (hs-cTnI) concentration within 48 hours after CABG (ng/L) (p=0.21).

Q: What does this research mean for the field?

Combined antegrade–retrograde blood cardioplegia does not significantly reduce peak postoperative high-sensitivity cardiac troponin I concentrations compared with antegrade-only cardioplegia in patients undergoing on-pump CABG for left main coronary artery disease. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Jelena Lesanovic; Milan Milojevic; Djordje Nikolic; Ivan Soldatovic; Dragana R. Unic-Stojanovic; Miroslav Miličić; Petar Vukovic; Ivana M. Petrovic; Sinisa Jagodic; Milovan Bojić; Slobodan Micovic

doi:10.3390/medicina62091799

September 18, 2026MedicinaOpen Access

Combined Antegrade–Retrograde Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting in Patients with Left Main Coronary Artery Disease: The CARDIOPROTECT-LMCAD Randomised Trial

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Key result

Combined antegrade-retrograde cardioplegia fails to reduce peak postoperative hs-cTnI compared with antegrade-only delivery in CABG.

P=0.21
n=60

Why the study?

Myocardial protection during on-pump CABG is critical in patients with LMCAD, where severe proximal stenosis may impair antegrade cardioplegia delivery, and the benefit of combined antegrade–retrograde cardioplegia is uncertain.

Does combined antegrade-retrograde blood cardioplegia reduce peak postoperative high-sensitivity cardiac troponin I (hs-cTnI) concentrations within 48 hours compared with antegrade-only blood cardioplegia in adults undergoing elective isolated on-pump CABG for significant left main coronary artery disease?

Study Design

Type

RCT (n=60)

Blinding

Single-blind (participants, postoperative clinical staff, laboratory personnel, and outcome assessors blinded; operating surgeon, anaesthesiologist, and perfusionist unblinded)

Randomization

1:1 ratio using a computer-generated allocation sequence via REDCap Randomisation Module

Multicenter

No

Structured PICO

Does combined antegrade-retrograde blood cardioplegia reduce peak postoperative high-sensitivity cardiac troponin I (hs-cTnI) concentrations within 48 hours compared with antegrade-only blood cardioplegia in adults undergoing elective isolated on-pump CABG for significant left main coronary artery disease?

P

Population

60 adults in Serbia undergoing elective isolated on-pump CABG for significant left main coronary artery disease (>=50% stenosis), free of concomitant or prior cardiac surgery, followed for 30 days.

I

Intervention

Combined antegrade-retrograde cold blood cardioplegia (4:1 blood-to-crystalloid ratio at 4-12 °C; induction 10 mL/kg up to 1000 mL split 2:1 between aortic root and coronary sinus catheter at 100-200 mL/min with pressure <=50 mmHg; maintenance ~40% of induction every 20-30 min; median antegrade volume 725 mL and retrograde volume 400 mL) plus terminal normothermic antegrade blood cardioplegia ('hot shot', 250 mL at 37 °C for 2 min before cross-clamp removal) and goal-directed cardiopulmonary bypass.

C

Comparator

Antegrade-only cold blood cardioplegia delivered exclusively via the aortic root at 200-300 mL/min (root pressure <=100 mmHg; median total volume 1300 mL) using the same 4:1 blood-crystalloid formulation, induction/maintenance protocol, terminal normothermic antegrade blood reperfusion ('hot shot'), and goal-directed cardiopulmonary bypass.

O

Outcome

Peak postoperative high-sensitivity cardiac troponin I (hs-cTnI) concentration during the first 48 hours after CABG (defined as the highest value measured at 4, 12, 24, or 48 hours after ICU admission).surrogate

Main Result

Absolute Event Rate: 394.1% vs 529.1%

p-value: p=0.21

Limitations

Single-centre trial with a small sample size of 60 patients powered for a biochemical rather than clinical endpoint
Observed hs-cTnI distribution and variability differed from sample-size estimation assumptions, potentially reducing statistical power
Intraoperative teams (surgeon, anaesthesiologist, perfusionist) were necessarily unblinded to treatment allocation
Residual between-group imbalances in aortic cross-clamp duration and baseline left ventricular end-diastolic diameter (LVEDD)
Secondary outcomes were exploratory and not adjusted for multiple comparisons
hs-cTnI reflects overall perioperative myocardial injury rather than cardioplegia-related injury alone
Single-centre trial of 60 patients powered for a biochemical rather than clinical endpoint
Intraoperative teams were necessarily unblinded to treatment allocation
Residual between-group imbalances in aortic cross-clamp duration and baseline LVEDD
Secondary outcomes were exploratory and not adjusted for multiplicity
Postoperative hs-cTnI reflects cumulative perioperative myocardial injury rather than cardioplegia-specific protection alone

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Answers are grounded in this paper and cite their sources.

Implication

Routine addition of retrograde blood cardioplegia to standard antegrade blood cardioplegia during elective on-pump CABG for left main coronary artery disease is safe and feasible but does not significantly reduce perioperative myocardial injury as measured by peak hs-cTnI, supporting an individualized rather than routine combined strategy.

Abstract

Background and Objectives: Myocardial protection during on-pump coronary artery bypass grafting (CABG) limits ischaemic injury, particularly in patients with left main coronary artery disease (LMCAD), in whom severe proximal stenosis may compromise antegrade cardioplegia delivery. We investigated whether combined antegrade–retrograde blood cardioplegia reduces postoperative high-sensitivity cardiac troponin I (hs-cTnI) concentrations, a marker of perioperative myocardial injury. Materials and Methods: We conducted a prospective, single-centre, randomised trial involving 60 adults undergoing elective isolated on-pump CABG for significant LMCAD. Patients were assigned (1:1) to antegrade-only or combined antegrade–retrograde blood cardioplegia. Cardiac biomarkers were measured after induction and at 4, 12, 24, and 48 h after ICU admission. The primary endpoint was peak hs-cTnI within 48 h; key secondary endpoints included the hs-cTnI area under the concentration–time curve, CK-MB, immediate myocardial electrical recovery and 30-day outcomes. Results: All patients received the assigned cardioplegia strategy, with no crossover. Peak hs-cTnI did not differ significantly between the antegrade-only and combined groups (median 529.1 [IQR 829.9] vs. 394.1 [503.4] ng/L; p = 0.21), nor did the hs-cTnI area under the concentration–time curve from 4 to 48 h (12,910.6 [23,127.4] vs. 8112.2 [11,686.2] ng·h/L; p = 0.16). Serial hs-cTnI, CK-MB, total creatine kinase, serum creatinine, immediate myocardial electrical recovery, and 30-day outcomes also did not differ significantly. No deaths, coronary sinus injuries, or other cardioplegia-related complications occurred. Conclusions: In patients undergoing isolated on-pump CABG for significant LMCAD, combined antegrade–retrograde blood cardioplegia did not significantly decrease peak hs-cTnI levels compared to the antegrade-only method. The combined approach was feasible with no cardioplegia-related complications, suggesting that an individualised strategy may be preferable to a routine one. Larger prospective studies are needed to determine whether higher-risk patients may derive greater benefit.

Discussion

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Cite This Study

Lesanovic et al. (2026) conducted an RCT in Significant left main coronary artery disease (LMCAD) undergoing elective isolated on-pump coronary artery bypass grafting (CABG) (n=60). Combined antegrade-retrograde blood cardioplegia vs. Antegrade-only blood cardioplegia via aortic root at 200-300 mL/min (pressure <=100 mmHg) with identical induction/maintenance dosing and terminal warm reperfusion was evaluated on Peak postoperative high-sensitivity cardiac troponin I (hs-cTnI) concentration within 48 hours after CABG (ng/L) (p=0.21). Combined antegrade-retrograde blood cardioplegia did not reduce peak postoperative hs-cTnI within 48 hours compared with antegrade-only cardioplegia.

synapsesocial.com/papers/6ac46e0697fdebb935c1880d https://doi.org/10.3390/medicina62091799

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Combined Antegrade–Retrograde Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting in Patients with Left Main Coronary Artery Disease: The CARDIOPROTECT-LMCAD Randomised Trial

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Combined Antegrade–Retrograde Cardioplegia for Myocardial Protection During Coronary Artery Bypass Grafting in Patients with Left Main Coronary Artery Disease: The CARDIOPROTECT-LMCAD Randomised Trial

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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