Minimally invasive mitral valve repair (MIMVR) through a right anterior minithoracotomy has become the reference standard in experienced centres because of its cosmetic benefits, reduced surgical trauma, and shorter hospital stay. In this setting, the ideal cardioplegic strategy is generally considered to be one that provides safe and prolonged myocardial protection with a single dose. The aim of this study was to compare Custodiol and Del Nido cardioplegia in terms of myocardial injury assessed by serial enzyme measurements and early postoperative events after MIMVR.

A retrospective single-centre cohort study was designed including 2490 patients operated on between 2014 and 2025. Very strict inclusion criteria were applied to obtain the most homogeneous cohort possible for the assessment of biochemical markers of myocardial injury. Exclusion criteria were mitral valve replacement, infective endocarditis, previous cardiac surgery, mitral regurgitation due to a mechanism other than prolapse (Carpentier type II), concomitant procedures, cardioplegia redosing, multiple repair attempts during the same operation, acute myocardial infarction within the previous 3 months, and urgent surgery.

After exclusions, 1:1 propensity score matching was performed, yielding a final sample of 778 cases (389 per group). All patients were operated on by the same surgical team, using identical protocols and the same approach: right anterior minithoracotomy with open or percutaneous femoral cannulation. The choice of cardioplegia was determined by the study period: in 2021, the department changed its routine protocol from Custodiol to Del Nido.

The primary end point was the quality of myocardial protection, assessed by postoperative CK and CK-MB measurements. The secondary end point analysed ventricular arrhythmias after aortic declamping requiring intraoperative cardioversion. Del Nido cardioplegia was associated with significantly lower postoperative CK and CK-MB levels, particularly during the first 24 hours (p < .001). Del Nido was also associated with a lower need for inotropic support at 6 hours, higher perioperative sodium levels, and fewer episodes of ventricular fibrillation after aortic declamping (p < .001). Major complications and 30-day mortality (0% in both groups) were similar.

The authors conclude that Del Nido provides superior myocardial protection based on myocardial injury markers and a lower incidence of arrhythmias after aortic declamping, with comparable overall clinical outcomes. They therefore consider it the preferred single-dose cardioplegic solution for low-complexity MIMVR.

COMMENTARY:

Several points of considerable interest can be drawn from this article regarding a procedure that is gaining increasing relevance in our departments and that represents the present and near future of the specialty: the minimally invasive approach.

The core of the debate focuses on a critical issue: cardioprotection during the ischaemic period. The study compares two widely used solutions in daily practice, whose main shared advantage is single-dose administration. This is a key point, as single-dose cardioplegia reduces technical complexity and avoids interruptions in an operation that is already more demanding for the surgeon than median sternotomy.

A brief review of the main features of both solutions is useful.

• Del Nido: initially developed for the paediatric population, it is a crystalloid-based solution combined with autologous blood in a 4:1 ratio. It induces depolarizing arrest, due to its high potassium content, but this is modulated by lidocaine, a sodium-channel blocker. It provides effective protection for up to 90 minutes with a single dose.
• Custodiol (HTK): this is a fully crystalloid intracellular-type solution. Unlike traditional cardioplegia, it achieves cardiac arrest through hyperpolarization of the myocardial membrane, owing to its low sodium and calcium content. Its main strength is that it provides a safe ischaemic window of up to 3 hours with a single infusion. Conversely, it has historically been associated with a higher incidence of ventricular arrhythmias after declamping and, because of the large infusion volume required, around 2 litres, with dilutional hyponatraemia.

The results reported by Greve et al. are clear and position Del Nido as a strategy associated with less direct myocardial injury, reflected by markedly lower CK and CK-MB curves during the first 12-24 postoperative hours, with differences that fade beyond 24 hours. Patients in the Del Nido group also required less early inotropic support and maintained more stable serum sodium levels.

Despite these striking enzymatic and metabolic differences during the first postoperative hours, the authors make it clear that they did not translate into differences in 30-day morbidity and mortality, which were identical in both arms (0%).

The more favourable enzyme profile observed with Del Nido may be partly explained by its 4:1 blood component, which provides some oxygen-carrying and buffering capacity to the tissues during myocardial ischaemia. However, it should be remembered that if the ischaemic time exceeds 90 minutes, redosing is mandatory. Another practical and relevant advantage of Del Nido is its cost-effectiveness, as it can be prepared as a compounded solution in the hospital pharmacy, unlike Custodiol, which is a more expensive ready-to-use commercial product.

From a methodological standpoint, the study is robust. This is one of the largest studies on cardioplegia published to date in the field of minimally invasive surgery, including 778 patients after matching. The use of propensity score adjustment adds substantial value by reducing the selection bias inherent to a retrospective study.

However, when analysing the limitations, we should be critical regarding the applicability of these results to daily clinical practice. The surgical exclusion criteria were so strict that the sample was reduced to an ideal scenario: elective mitral repairs, exclusively for prolapse (Carpentier II), with a single aortic cross-clamp period and no need for redosing. By excluding complex, urgent, or high-risk cases, the results reflect a highly controlled setting.

In conclusion, the study shows that Del Nido cardioplegia is an excellent and probably preferable option for low-complexity MIMVR. The clinical challenge remains to determine whether this advantage is maintained when the surgeon faces prolonged myocardial ischaemic times and more complex mitral anatomies.

REFERENCE:

Greve D, Akansel S, Holler J, Dini M, Miskinyte E, Hinkov H, et al. Custodiol Versus Del Nido Cardioplegia in Minimally Invasive Mitral Valve Repair-a Propensity Score-Matched Study. Interdiscip CardioVasc Thorac Surg. 2026; doi: 10.1093/icvts/ivag074.