Evaluation of the Effective Myocardial Protection Duration of Del Nido Cardioplegia: A Prospective Observational Study in Adult Patients Undergoing Cardiac Surgery
Evaluation of the Effective Myocardial Protection Duration of Del Nido Cardioplegia: A Prospective Observational Study in Adult Patients Undergoing Cardiac Surgery
This single-center, prospective, observational cohort study quantifies the effective myocardial protection window of Del Nido cardioplegia during adult open-heart surgery performed under cardiopulmonary bypass (CPB) and aortic cross-clamp (ACC). Without altering routine care, time-stamped high-sensitivity cardiac troponin (hs-cTn) measurements will be obtained at predefined intraoperative and early postoperative intervals to identify the inflection ("change-point") at which biochemical evidence of ischemic injury begins to rise. Eighty adults undergoing elective valve and/or thoracic aortic procedures with Del Nido cardioplegia will be enrolled. The primary endpoint is the intraoperative hs-cTn change-point time referenced to ACC. Secondary endpoints include associations between change-point and ACC duration, the presence/timing of any re-dose, and early clinical outcomes (e.g., low cardiac output syndrome, maximum VIS in the first 24 h, new arrhythmia or pacemaker need, acute kidney injury by KDIGO, ventilation hours, ICU/hospital length of stay, 30-day MACE and mortality). All cardioplegia choices (dose, route, temperature, re-dose decisions) remain per standard practice; no experimental therapy is administered. Risks are minimal and limited to small-volume blood sampling coordinated with routine draws.
Background and Rationale Del Nido cardioplegia is widely used in adult valve/aortic surgery to permit prolonged single-dose electrical arrest. The effective protection duration likely varies with patient and procedural factors (e.g., LV function, temperature, hemodilution, surgical complexity, antegrade/retrograde delivery). Many centers empirically re-dose around 60-90 minutes; however, this window may not be optimal for every case. The current study quantifies the protection window by coupling routine care with dense, time-stamped hs-troponin sampling.
Design and Setting Prospective, single-center, observational cohort conducted at Necmettin Erbakan University, Department of Cardiovascular Surgery (Türkiye).
Population Adults 18-80 years scheduled for elective valve and/or thoracic aortic surgery under CPB with ACC in which Del Nido cardioplegia is used per institutional routine. Key exclusions include isolated or CABG-dominant procedures, redo sternotomy, emergency/salvage or preoperative shock, IABP/ECMO, LVEF <35%, eGFR <45 mL/min/1.73 m², significant pulmonary or hepatic disease, major coagulopathy, active infection/sepsis or endocarditis, pregnancy, and preoperative troponin elevation.
Interventions None. Cardioplegia content, dose, route (antegrade/retrograde/combined), temperature, and re-dose decisions are entirely per standard practice at the discretion of the surgical/anesthesia/perfusion team. No experimental therapy is administered.
Sampling Schedule (Biomarkers) Preoperative baseline hs-cTn; intraoperative sampling referenced to ACC at 0, 30, and 60 minutes, then intensified at 75, 90, 105, and 120 minutes. If a re-dose is administered, additional samples at pre-re-dose and +15/+30/+45/+60 minutes. Postoperative hs-cTn at approximately 6, 24, and 48 hours. Intraoperative blood is obtained preferably from the venous reservoir or existing central lines. Each draw ~3-5 mL; total additional volume ~30-40 mL. Exploratory CK-MB may be recorded where available.
Outcomes Primary outcome: intraoperative hs-cTn change-point time (minutes from ACC) identified by segmented (piecewise) trend analysis indicating the earliest sustained acceleration compatible with evolving ischemic injury.
Key secondary outcomes: (i) association between change-point and ACC duration; (ii) presence/timing of Del Nido re-dose and biochemical response to re-dose (slope change pre/post); (iii) early clinical outcomes including low cardiac output syndrome, maximum VIS in the first 24 h, new arrhythmia or pacemaker need, acute kidney injury by KDIGO, ventilation hours, ICU/hospital length of stay, re-exploration/bleeding, infection, 30-day MACE, and 30-day all-cause mortality.
Statistical Plan (Summary) Individual time series will be analyzed using segmented (piecewise) regression and/or change-point detection methods. Group-level estimates (mean protection window and variance) will be obtained via mixed-effects change-point models. Associations with durations (ACC, CPB), re-dose timing, and outcomes will use linear/quantile regression and logistic/Poisson/negative binomial models as appropriate. Missing data will be handled per predefined rules and, if needed, multiple imputation. Target enrollment is 80 participants, anticipated to provide ~80% power at α=0.05 to detect a clinically meaningful change-point and slope shift in hs-troponin trajectories.
Safety and Data Handling Risk is minimal and limited to low-volume blood sampling aligned with routine care; no experimental treatment is given. Data are recorded on standardized case report forms and stored in secure, de-identified systems compliant with local regulations. Serious adverse events are reported per institutional/authority requirements.
Significance By quantifying the actual protection window and its variability, the study is designed to inform more rational-potentially individualized-re-dose timing for Del Nido cardioplegia, aiming to reduce both under-protection (late re-dose) and workflow disruption (unnecessary early re-dose).
Inclusion Criteria:
Exclusion Criteria: