Effective Myocardial Protection Time of Del Nido Cardioplegia in Adult Cardiac Surgery

NCT ID: NCT07249424

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-11-12
• Study Completion Date: 2026-03-01

Brief Summary

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.

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).

Conditions

Heart Valve Diseases; Aortic Diseases; Myocardial Ischemia; Reperfusion Injury, Myocardial; Postoperative Complications (Cardiopulmonary); Cardiopulmonary Bypass

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Muhammet Talha Ceran, MD

OTHER

Sponsor Role: lead

Responsible Party

Muhammet Talha Ceran, MD

Cardiovascular Surgery Resident, Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Yüksel Dereli, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Necmettin Erbakan University, Dept. of Cardiovascular Surgery

Muhammet Talha Ceran

Role: PRINCIPAL_INVESTIGATOR

Necmettin Erbakan University, Dept. of Cardiovascular Surgery

Locations

Necmettin Erbakan University Meram Faculty of Medicine

Konya, Konya, Turkey (Türkiye)

Site Status: RECRUITING

Countries

Turkey (Türkiye)

Central Contacts

Muhammet Talha Ceran

Role: CONTACT

mtceran@gmail.com

+905426880431

Yüksel Dereli

Role: CONTACT

hastane@erbakan.edu.tr

+903322236861

Facility Contacts

Muhammet Talha Ceran, MD

Role: primary

mtceran@gmail.com

+905426880431

Yüksel Dereli, MD (Prof.)

Role: backup

yuxel.dereli@gmail.com

+905438703843 ext. +903322236258

References

Januzzi JL Jr. Troponin testing after cardiac surgery. HSR Proc Intensive Care Cardiovasc Anesth. 2009;1(3):22-32.

Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Behrendt T. Scanning densitometer for photographic fundus measurements. Am J Ophthalmol. 1966 Oct;62(4):689-93. doi: 10.1016/0002-9394(66)92195-7. No abstract available.

Reference Type: RESULT

PMID: 5929134 (View on PubMed)

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Reference Type: RESULT

PMID: 40286361 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32387781 (View on PubMed)

Other Identifiers

E-40209705-050.01-1123786

Identifier Type: -

Identifier Source: org_study_id