Effective Myocardial Protection Time of Del Nido Cardioplegia in Adult Cardiac Surgery (DN-TIME-2025)

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Ischemia; Heart Valve Diseases; Cardiopulmonary Bypass; Aortic Diseases; Reperfusion Injury, Myocardial; Postoperative Complications (Cardiopulmonary)

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Konya
    • Konya, Konya, Turkey (Türkiye), 42080
      • Necmettin Erbakan University Meram Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Single-center, tertiary academic cardiovascular surgery service at Necmettin Erbakan University Meram Medical Faculty Hospital (Konya, Türkiye). Consecutive adults (18-80 years) undergoing elective valve and/or thoracic aortic surgery with cardiopulmonary bypass and aortic cross-clamping, in whom Del Nido cardioplegia is used as part of routine care, are screened and, if eligible, approached for written informed consent. Approximately 80 participants are enrolled and followed through the index hospitalization; 30-day outcomes are abstracted from the medical record/standard follow-up. Observational cohort; no randomization; all treatment decisions per usual care.

Description

Inclusion Criteria:

• Age 18-80 years
• Elective valve surgery (aortic, mitral, tricuspid), thoracic aortic surgery, or combined valve + thoracic aortic procedures
• Planned cardiopulmonary bypass (CPB) with aortic cross-clamp (ACC)
• Use of Del Nido cardioplegia per institutional routine
• Ability to provide written informed consent (participant or legally authorized representative)

Exclusion Criteria:

• Isolated CABG or CABG-dominant combined procedures
• Redo sternotomy
• Emergency status (including shock) or preoperative mechanical circulatory support (IABP or ECMO), or anticipated need for such support
• Left ventricular ejection fraction <35%
• Estimated GFR <45 mL/min/1.73 m²
• Moderate-severe chronic lung disease with significant functional limitation, or severe pulmonary hypertension
• Active infection/sepsis or active infective endocarditis
• Severe hepatic dysfunction, major coagulopathy, or bleeding diathesis
• Pregnancy
• Deep hypothermia protocols (<28 °C)
• Procedures without ACC
• Preoperative cardiac troponin above the laboratory upper reference limit
• Any condition that, in the judgment of the treating team, would preclude safe participation or protocol adherence

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Del Nido Cardioplegia Cohort; Adults undergoing elective valve and/or thoracic aortic surgery under CPB with ACC in which Del Nido cardioplegia is used per routine practice. No experimental therapy; only study-specific blood sampling for hs-troponin at predefined times.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative hs-troponin change-point time (minutes from ACC)	For each participant, serial hs-cTn values obtained at ACC 0/30/60/75/90/105/120 minutes (and at re-dose pre/+15/+30/+45/+60 when applicable) will be modeled with segmented (piecewise) regression. The change-point is defined as the earliest time with a statistically significant increase in slope indicating evolving myocardial injury. Unit: minutes; lower values reflect earlier loss of protection.	From aortic cross-clamp (ACC) application to 120 minutes intraoperatively; if a re-dose is given, up to 60 minutes after the re-dose within the same operation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical response to re-dose (slope change in hs-troponin)	Within-subject comparison of hs-cTn trajectory slope before vs after re-dose using segmented regression. Metric: difference in slopes (ng/L per minute).	From re-dose (time 0) to +60 minutes intraoperatively.
Peak postoperative hs-troponin (0-48 h)	Maximum measured hs-cTn (ng/L) within the first 48 hours after surgery.	From end of surgery to 48 hours postoperatively (samples ~6, 24, 48 h).
Low Cardiac Output Syndrome (LCOS) within 24 hours	LCOS defined as any of the following: (a) maximum vasoactive-inotropic score (VIS) ≥15 for ≥2 consecutive hours; or (b) initiation of mechanical circulatory support (IABP/ECMO); or (c) cardiac index <2.2 L/min/m² with clinical hypoperfusion requiring inotrope/vasopressor escalation. Outcome reported as proportion of participants meeting criteria.	First 24 postoperative hours.
30-day major adverse cardiovascular events (MACE)	Composite of all-cause death, non-fatal myocardial infarction (per institutional cardiac-surgery definition), and stroke/TIA. Reported as proportion of participants; components also summarized separately.	30 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between change-point time and ACC duration	Linear/quantile regression of change-point time (min) on ACC duration (min). Effect size reported as β per 10-min increase in ACC with 95% CI.	Intraoperative (from ACC on to 120 min; re-dose window as applicable)
Immediate reperfusion arrhythmia after ACC removal	Incidence of VF/VT requiring defibrillation or temporary pacing. Reported as proportion; association with change-point explored.	From ACC removal to 30 minutes after reperfusion

Collaborators and Investigators

• Sponsor: Muhammet Talha Ceran, MD
• Investigators: Principal Investigator: Yüksel Dereli, Prof. Dr., Necmettin Erbakan University, Dept. of Cardiovascular Surgery; Principal Investigator: Muhammet Talha Ceran, Necmettin Erbakan University, Dept. of Cardiovascular Surgery

Publications and helpful links

General Publications

• McGrath S, Alaour B, Kampourakis T, Marber M. Cardiac Troponin: Fragments of the Future? JACC Adv. 2025 May;4(5):101695. doi: 10.1016/j.jacadv.2025.101695. Epub 2025 Apr 25.
• Nakao M, Morita K, Shinohara G, Kunihara T. Modified Del Nido Cardioplegia and Its Evaluation in a Piglet Model. Semin Thorac Cardiovasc Surg. 2021 Spring;33(1):84-92. doi: 10.1053/j.semtcvs.2020.03.002. Epub 2020 May 7.
• Januzzi JL Jr. Troponin testing after cardiac surgery. HSR Proc Intensive Care Cardiovasc Anesth. 2009;1(3):22-32.
• Eris C, Engin M, Erdolu B, Kagan As A. Comparison of del Nido Cardioplegia vs. blood cardioplegia in adult aortic surgery: Is the single-dose cardioplegia technique really advantageous? Asian J Surg. 2022 May;45(5):1122-1127. doi: 10.1016/j.asjsur.2021.09.032. Epub 2021 Oct 12.
• Devereaux PJ, Lamy A, Chan MTV, Allard RV, Lomivorotov VV, Landoni G, Zheng H, Paparella D, McGillion MH, Belley-Cote EP, Parlow JL, Underwood MJ, Wang CY, Dvirnik N, Abubakirov M, Fominskiy E, Choi S, Fremes S, Monaco F, Urrutia G, Maestre M, Hajjar LA, Hillis GS, Mills NL, Margari V, Mills JD, Billing JS, Methangkool E, Polanczyk CA, Sant'Anna R, Shukevich D, Conen D, Kavsak PA, McQueen MJ, Brady K, Spence J, Le Manach Y, Mian R, Lee SF, Bangdiwala SI, Hussain S, Borges FK, Pettit S, Vincent J, Guyatt GH, Yusuf S, Alpert JS, White HD, Whitlock RP; VISION Cardiac Surgery Investigators. High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality. N Engl J Med. 2022 Mar 3;386(9):827-836. doi: 10.1056/NEJMoa2000803.
• Ad N,Holmes SD,Massimiano PS,Rongione AJ,Fornaresio LM,Fitzgerald D

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2025
• Primary Completion (Actual): January 15, 2026
• Study Completion (Actual): February 16, 2026

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: ischemia-reperfusion; valve surgery; cardioplegia; myocardial protection; cardiopulmonary bypass (CPB); high-sensitivity troponin; thoracic aortic surgery; Del Nido cardioplegia; aortic cross-clamp (ACC); aortic cross-clamp time; single-dose cardioplegia
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Cardiomyopathies; Reperfusion Injury; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Postoperative Complications; Heart Valve Diseases; Aortic Diseases; Myocardial Reperfusion Injury
• Other Study ID Numbers: E-40209705-050.01-1123786

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the primary and key secondary outcomes (time-stamped hs-troponin values, basic demographics, operative variables, and early postoperative outcomes). Data will be shared in compliance with local regulations (e.g., KVKK) and institutional policies.
• IPD Sharing Time Frame: Available beginning 6-12 months after the primary publication (or within 12 months after last-patient-last-visit if no publication) and will remain available for 5 years.

IPD Sharing Access Criteria

Qualified researchers may request access by submitting a brief proposal to the Central Contact. Requests will be reviewed by the study investigators and the institutional Data Access Committee. Upon approval and execution of a Data Use Agreement (non-reidentification, secure storage, academic use only, citation/acknowledgment, and data destruction at project end), de-identified IPD and supporting documents will be transferred via secure link.

Central Contact: Muhammet Talha Ceran, MD - mtceran@gmail.com

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No