Cardioplegia Strategies in Minimally Invasive Aortic Valve Replacement: An Inverse Probability of Treatment Weighting Analysis

This 2026 Medicina study examines one of the most practical unresolved questions in minimally invasive aortic valve replacement: which cardioplegia strategy offers the best myocardial protection without sacrificing safety? The authors retrospectively analyzed 543 consecutive patients treated at a single center between January 2010 and April 2025, comparing four commonly used cardioplegia approaches: Buckberg, Calafiore, Custodiol HTK, and St. Thomas’. Because the groups differed substantially at baseline, the investigators used inverse probability of treatment weighting, or IPTW, based on a multinomial propensity model to create a more balanced pseudo-population before comparing outcomes. That statistical step is central to the paper, because the raw cohort had important imbalances in age, coronary artery disease, valve pathology, smoking status, and bicuspid anatomy. After weighting, those imbalances were reported as adequately corrected. 

The clinical context matters. Minimally invasive aortic valve replacement can reduce pain, shorten recovery, and improve cosmetic outcomes compared with full sternotomy, but it also creates technical constraints. In a smaller operative field, cross-clamp and bypass times may lengthen, making myocardial protection especially important. Cardioplegia choice becomes more than a routine preference; it can affect rhythm stability, biomarker release, and intraoperative workflow. The four strategies compared in this study reflect the main options surgeons use in practice: warm blood cardioplegia with Calafiore, cold blood cardioplegia with Buckberg, and crystalloid-based arrest with Custodiol HTK or St. Thomas’. 

The most important finding is that Calafiore and Custodiol performed better than Buckberg for several early postoperative endpoints after weighting. New-onset atrial fibrillation was markedly lower with Calafiore and especially Custodiol than with Buckberg. In the IPTW-balanced analysis, postoperative AF occurred in 28.5% of Buckberg patients, compared with 9.3% for Calafiore and 3.8% for Custodiol. Respiratory insufficiency showed a similar pattern, with Buckberg again performing worse. The same general separation appeared for broader arrhythmia outcomes, suggesting that the differences were not limited to one isolated rhythm measure. These are clinically meaningful findings because atrial fibrillation after cardiac surgery is common, costly, and associated with downstream complications. 

Biochemical evidence of myocardial injury also favored Calafiore and Custodiol. Peak postoperative CK levels were substantially higher with Buckberg and St. Thomas’ than with Calafiore and Custodiol. Peak CK-MB followed the same direction. In practical terms, that suggests less myocardial injury or at least a gentler perioperative biomarker profile with the Calafiore and Custodiol strategies. Interestingly, the study did not find major differences in postoperative left ventricular ejection fraction, indicating that standard echocardiographic recovery looked broadly similar despite the biomarker divergence. That makes the enzyme and rhythm findings even more important, since LVEF alone may be too blunt to detect meaningful differences in myocardial protection quality. 

One of the paper’s more nuanced contributions is its attempt to separate cardioplegia effects from case complexity. The authors note that bicuspid anatomy prolonged operative metrics independently, yet it did not appear to drive the biomarker differences. They also performed sensitivity analyses that included procedural times and examined isolated aortic valve replacement cases separately. Even after those adjustments, the main signal remained: Calafiore and Custodiol were associated with lower AF, lower biomarker release, and fewer respiratory complications, while mortality and major complications remained similar across groups. That strengthens the argument that the observed benefits may not be explained solely by operative duration or concomitant procedures. 

At the same time, the study does not prove causality. It is retrospective, single-center, and non-randomized. Cardioplegia selection depended on surgeon preference and institutional practice, and those practices evolved over a 15-year period. Even with IPTW, unmeasured confounding remains possible. Surgeon experience, era effects, changes in perioperative care, and subtle selection biases could all influence the results. Another limitation is the absence of systematic troponin analysis, which would have provided a more sensitive marker of myocardial injury than CK or CK-MB. The authors are appropriately cautious and frame their conclusions as robust associations rather than definitive causal proof. 

From an SEO and practice perspective, this study is notable because it speaks directly to decision-making in minimally invasive cardiac surgery. Surgeons choosing between blood and crystalloid cardioplegia, or between single-dose and repeated-dose workflows, often want evidence that applies to real-world minimally invasive aortic valve replacement rather than mixed cardiac surgery cohorts. This paper suggests that Calafiore and Custodiol may offer a favorable balance of myocardial protection, rhythm outcomes, and respiratory recovery without worsening mortality, stroke, ICU stay, or hospital length of stay. For clinicians, it supports thoughtful protocol selection. For researchers, it sets up the obvious next step: a prospective randomized trial focused specifically on minimally invasive AVR.