Determinants of Inadequate Cardioprotection in Adult Patients with Left Ventricular Dysfunction

Abstract

Background Perioperative cardioprotection is essential for achieving satisfactory clinical outcomes in heart failure patients. It is important to understand the factors affecting perioperative cardioprotection.

Methods The institutional database was searched for patients with reduced ejection fraction (EF, < 40%) who underwent surgery with cardioplegia-induced arrest. Patients were divided into del Nido cardioplegia (DN) and cold blood cardioplegia (CB) groups. The relationships between age, preoperative blood parameters, creatinine, cross-clamp time (CCT), extracorporeal circulation time (ECT), and postoperative troponin values at 12 hours or deterioration of EF (≥5%) were evaluated. Baseline characteristics, operative parameters, and outcomes were analyzed.

Results There were 508 patients with reduced EF (331 DN and 177 CB). In the entire cohort, anemic patients had greater troponin values (p = 0.004) as well as in the DN group (p = 0.002). However, this was not detected in the CB group (flat regression line; p = 0.674). Patients with high leukocyte values had greater troponin release (entire cohort: p < 0.001; DN group: p < 0.001; CB group: steep regression line with p = 0.042). Longer CCT and ECT were associated with greater troponin release (entire cohort; both groups) and greater risk of fall in EF. In a direct comparison, fewer patients had significant deterioration of EF in the DN group than CB group (3.9 vs. 11.9%; p < 0.001).

Conclusion The use of CB cardioplegia may be beneficial in anemic patients, whereas the use of DN cardioplegia may be beneficial for expected long CCT and high leukocytosis.

Keywords

cardioprotection - cardioplegia - heart failure - cardiopulmonary bypass

Introduction

Proper preservation of the myocardium during intraoperative ischemia is a critical predictor of satisfactory clinical outcomes. However, there can be huge diversity in the degree of myocardial damage among patients who receive the same cardioplegic solution. The efficacy of cardioplegia-induced arrest can be affected by other factors, which may become apparent in the most demanding clinical scenarios, such as patients with impaired contractility at baseline. This study aims to identify those factors and assess their impact on postoperative myocardial damage.

Cardioprotection is important in patients with heart failure,[1] and the impact of inadequate cardioprotection is particularly pronounced in this patient population. At our facility, two well-established protocols are used for cardioplegia in these cases, namely the del Nido cardioplegia (DN) and cold blood cardioplegia (CB). The DN was designed in Pittsburgh by Pedro del Nido and his team and has since been used in Boston Children's Hospital with good results.[2] There are several prospective trials on the use of the del Nido protocol, but none specifically address patients with significantly impaired contractility.[3] [4] [5] Therefore, current guidelines on cardiopulmonary bypass in adult cardiac surgery recommend the application of the DN protocol in low-risk cases with short aortic cross-clamp times (CCTs) to minimize surgical interruptions caused by repeated perfusion of cardioplegia.[6] Blood cardioplegia has a longer history, and its efficacy is well documented. It has been used since Follette et al first reported their results,[7] and many surgeons still consider it the most efficient protocol, particularly in ischemic or damaged myocardium, supported by clinical studies.[1]

At our institution, the decision on whether to use DN or CB is made by the surgeon, and each case is treated individually. Factors that are taken into consideration include the complexity of the procedure and the estimated duration of the CCT, the possibility of fluid overload in patients with heart failure or kidney disease, the possibility of allergies to lidocaine, the rationale to provide additional cardioplegia doses (selective graft perfusion), and the patient's blood morphology parameters.

Due to the differences in protocols, it is necessary to address the entire cohort and evaluate the impact of the analyzed determinants for each cardioplegia separately. The leading hypothesis is that patients' baseline characteristics and operative determinants may impact the efficacy of cardioprotection during surgery. However, this effect may vary depending on the solution used.

Methods

Data Collection

The institutional registry was searched for patients with an ejection fraction (EF) of less than 40%, below the defined threshold for heart failure with a reduced EF. Although the main aim of the analysis was not to directly compare cardioplegic solutions, the entire cohort was divided into two groups: the DN group and CB group, to assess potential differences in the impact of analyzed factors on the efficacy of both strategies.

Cardioprotection Protocols

The DN solution is prepared by a perfusionist using manufactured components to obtain a compound identical to the one Pedro del Nido and his team designed. The components include Plasma-Lyte A (1,000 mL), 20% mannitol (16.3 mL), 50% MgSO₄ (4 mL), 8.4% NaHCO₃ (13 mL), 2 mEq/mL KCl (13 mL), and 1% lidocaine (13 mL). As a result, the crystalloid part (1,059 mL) contains 153 mEq sodium, 31 mEq potassium, 19.24 mEq magnesium, 13 mEq bicarbonate, 124 mEq chloride, 27 mEq acetate, 23 mEq gluconate, 0.13 g lidocaine, and 3.26 g mannitol. Before delivery, the solution is combined with the patient's blood in a ratio of 4:1 (crystalloid:blood). The protocol details are summarized in [Table 1].

Table 1 Cardioprotection protocols comparison

	del Nido cardioplegia protocol	Cold blood cardioplegia protocol
Blood: crystalloid ratio	1:4	4:1
Routine delivery	Antegrade; intermittent	Antegrade; intermittent
Infusion volume (after blood:crystalloid mixture)	20 mL/kg for 90 min of cross-clamp, subsequent doses of 25–30% of initial dose	15 mL/kg; subsequent doses of 5 mL/kg every 20–25 min
Infusion temperature (°C)	4–8	4–8
Infusion pressure (mm Hg)	100–200	100–200
Infusion flow (mL/min)	200–300	200–300

The second solution involves preparing 500 mL of crystalloid from Plasma-Lyte A (435 mL), 15% mannitol (20 mL), 8.4% NaHCO₃ (20 mL), and 2 mEq/mL KCl (25 mL). This solution contains 81 mEq sodium, 52 mEq potassium, 1.3 mEq magnesium, 20 mEq bicarbonate, 92.6 mEq chloride, 11.7 mEq acetate, 10 mEq gluconate, and 3 g mannitol. Before infusion, the solution is mixed with autologous patient blood at a ratio of 1:4 (crystalloid:blood). The protocol details are summarized in [Table 1].

Primary Outcomes

The primary outcomes of the study were to determine the relationship between postoperative high-sensitivity troponin T (hs-TnT) levels and analyzed determinants, including preoperative blood morphology parameters, age, length of cross-clamp and extracorporeal circulation time (ECT), and preoperative creatinine. The analysis was conducted separately for the entire cohort and each group (DN and CB). Troponin measurements were taken preoperatively, at 12 and 36 hours following the surgical procedure in each case, using a hs-TnT measurement kit (Roche, Basel, Switzerland) with reference laboratory values of 0 to 14 pg/mL.

The study also aimed to determine the relationship between the fall in EF and analyzed determinants of adequate cardioprotection, including preoperative blood morphology parameters, age, length of cross-clamp and ECT, and preoperative creatinine. The analysis was conducted separately for the entire cohort and each group (DN and CB). In each case, a complete echocardiographic evaluation was performed preoperatively and 3 days following the surgical procedure by two cardiologists coworking during the whole study period. The EF was estimated with Simpson's method to standardize the results, and a fall in EF of 5% was considered significant.

Secondary Observations

Secondary observations were conducted separately for the entire cohort and each group to provide clinical context. These observations included mortality, myocardial infarction (according to the fourth universal definition of myocardial infarction[8]), cerebrovascular incidents, major adverse cardiac and cerebrovascular events (MACCE, defined as the composite endpoint of death, myocardial infarction, and cerebrovascular incident), use of intra-aortic balloon pump (IABP), kidney injury (defined according to the Acute Kidney Injury Network as stage 1 with a creatinine increase of >0.3 mg/dL or 150 to 200%, stage 2 with a creatinine increase of 200 to 300%, and stage 3 with a creatinine increase of >300%), and other perioperative complications.

Research Ethics Board Consent

The calculations for this study were based on a retrospective, deidentified dataset analysis, and no additional interventions were made. The dataset was created from the institutional registry of patients who had consented to data analysis for medical and scientific purposes. As such, following the National Code on Clinical Trials (National Code on Clinical Researches, 2011), no formal research ethics board approval was mandatory for the quantitative part of the study.

Statistical Analysis

The data are presented as median (interquartile range). Categorical data were compared using the chi-square test, and continuous data were compared using the Mann–Whitney test. A p-value of less than 0.05 was considered statistically significant.

Linear regression was used to determine the relationship between age, blood morphology parameters, creatinine, ECT, CCT, and troponin values. A logarithmic transformation was used for troponin values. The D'Agostino–Pearson test was used to verify normal data distribution. Probit regression was used to determine the risk of a fall in EF concerning age, blood morphology parameters, creatinine, ECT, CCT, and troponin values.

Statistical analysis was performed using MedCalc v.18.5 (MedCalc Software, Ostend, Belgium).

Results

A database search revealed that between 2014 and 2021, seven cardiac surgeons operated on 8,981 patients using extracorporeal circulation. Of these patients, 508 cases (5.6%) had significantly impaired contractility (EF < 40%) and are being further considered for this study. The surgeons used DN in 331 patients (65.2%), whereas CB was used in 177 patients (34.8%).

At baseline, there were no differences in clinical and laboratory parameters and perioperative risk between the groups ([Table 2]). However, patients in the DN group had a greater median intraventricular septum and posterior wall diameter, with a difference in medians of 1 mm ([Table 3]). There were no significant differences in surgical procedures between the groups ([Table 4]), although there was a trend favoring the use of CB in isolated coronary surgery ([Table 4]).

Table 2 Baseline patient characteristics

	DN (331)	CB (177)	p	All (508)
Age	70.0 (64.0–75.0)	69.0 (61.0–75.0)	0.366	70.0 (63.0–75.0)
Male gender	261 (78.8%)	137 (77.4%)	0.705	398 (78.3%)
Coronary artery disease	241 (72.8%)	134 (75.7%)	0.479	375 (73.8%)
Infective endocarditis	3 (0.9%)	1 (0.6%)	0.679	4 (0.8%)
MVI	195 (58.9%)	90 (50.8%)	0.081	285 (56.1%)
MVS	7 (2.1%)	3 (1.7%)	0.746	10 (1.9%)
TVI	89 (26.9%)	35 (19.8%)	0.076	124 (24.4%)
AVS	61 (18.4%)	27 (15.2%)	0.368	88 (17.3%)
AVI	27 (8.2%)	11 (6.2%)	0.428	38 (7.5%)
Aortic aneurysm	9 (2.7%)	5 (2.8%)	0.945	14 (2.7%)
History of MI	92 (27.8%)	57 (32.2%)	0.299	149 (29.3%)
MI on admission	46 (13.9%)	16 (9.0%)	0.111	62 (12.2%)
History of PCI	52 (15.7%)	32 (18.1%)	0.494	84 (16.5%)
Paroxysmal AF	57 (17.2%)	25 (14.1%)	0.367	82 (16.1%)
Persistent/permanent AF	21 (6.3%)	14 (7.9%)	0.507	35 (6.9%)
Diabetes	50 (15.1%)	34 (19.2%)	0.236	84 (16.5%)
Hyperlipidemia	85 (25.7%)	54 (30.5%)	0.245	139 (27.4%)
Arterial hypertension	179 (54.1%)	106 (59.9%)	0.209	285 (56.1%)
Obesity	27 (8.1%)	17 (9.6%)	0.581	44 (8.7%)
Active smoking	20 (6.0%)	9 (5.1%)	0.658	29 (5.7%)
Kidney disease	27 (8.2%)	20 (11.3%)	0.245	47 (9.2%)
Median creatinine (mg/dL)	1.2 (1.0–1.4)	1.2 (1.0–1.3)	0.228	1.2 (1.0–1.4)
Dialysis	2 (0.6%)	0	0.301	2 (0.4%)
Asthma/COPD	15 (4.5%)	11 (6.2%)	0.413	26 (5.1%)
Euroscore II (%)	3.2 (1.7–5.2)	3.6 (2.3–5.2)	0.085	3.5 (1.9–5.2)
hs-Troponin T (pg/mL)	25.1 (15.20 79.7)	31.5 (16.9–73.5)	0.339	28.6 (15.9–76.1)
Blood morphology parameters
Hemoglobin (g/dL)	14.1 (12.7–15.0)	13.7 (12.3–14.8)	0.326	13.9 (12.5–14.9)
Hematocrit (%)	41.5 (37.9–44.7)	41.1 (36.9–44.3)	0.176	41.4 (37.5–44.4)
Red blood cell count (×1012/L)	4.5 (4.2–4.8)	4.4 (4.0–4.7)	0.064	4.5 (4.1–4.8)
White blood cell count (×109/L)	7.8 (6.3–9.6)	7.9 (6.4–9.4)	0.882	7.8 (6.3–9.5)
Platelet count (×109/L)	189.0 (149.7–235.0)	190.0 (156.0–221.0)	0.700	189.0 (153.0–231.0)

Abbreviations: AF, atrial fibrillation; AVI, aortic valve insufficiency; AVS, aortic valve stenosis; CK-MB, creatine kinase (MB isoenzyme); CB, cold blood cardioplegia; COPD, chronic obstructive pulmonary disease; DN, del Nido cardioplegia; EF, ejection fraction; hsTnT, high-sensitivity troponin T; MI, myocardial injury; MVI, mitral valve insufficiency, MVS, mitral valve stenosis; PCI, percutaneous coronary intervention; TVI, tricuspid valve insufficiency.

Note: Data are presented as number (percentage) and median (interquartile range).

Table 3 Preoperative and postoperative echocardiographic parameters

	DN (331)	CB (177)	p	All (508)
Preoperative
EF (%)	30.0 (25.0–35.0)	30.0 (25.0–35.0)	0.627	30.0 (25.0–35.0)
Left atrium (mm)	46.0 (43.0–51.7)	45.0 (41.0 50.0)	0.131	46.0 (42.0–50.0)
LV-EDD (mm)	62.0 (58.0–69.0)	64.0 (59.0–68.0)	0.906	63.0 (59.0–68.0)
LV-ESD (mm)	49.0 (43.0–55.0)	48.0 (40.0–54.0)	0.291	49.0 (41.0–55.0)
Right ventricle (mm)	27.0 (24.0–30.0)	26.0 (24.0–30.0)	0.956	26.0 (24.0–30.0)
Posterior wall (mm)	12.0 (11.0–12.0)	11.0 (10.0–11.0)	<0.001	11.0 (10.0–12.0)
IVS (mm)	12.0 (11.0–12.0)	11.0 (10.0–12.0)	0.046	12.0 (10.0–12.0)
Postoperative
EF (%)	35.0 (27.2–35.0)	30.0 (25.0–38.0)	0.875	35.0 (25.0–35.7)
Left atrium (mm)	45.0 (40.0–48.0)	44.0 (40.0–48.0)	0.399	45.0 (40.0–48.0)
LV-EDD (mm)	60.0 (56.0–66.0)	60.0 (57.0–68.0)	0.366	60.0 (56.0–66.0)
LV-ESD (mm)	45.5 (40.0–50.0)	46.0 (40.0–50.0)	0.953	46.0 (40.0–50.0)
Right ventricle (mm)	24.0 (23.0–29.0)	26.0 (24.0–30.0)	0.002	25 (24.0–29.0)
Posterior wall (mm)	12.0 (11.0–12.0)	11.0 (10.0–11.0)	<0.001	12.0 (11.0–12.0)
IVS (mm)	12.0 (11.0–12.0)	11.0 (10.0–12.0)	0.002	12.0 (11.0–12.0)

Abbreviations: CB, cold blood cardioplegia; DN, del Nido cardioplegia; EF, ejection fraction; IVS, intraventricular septum; LV-EDD, left ventricular end diastolic diameter; LV-ESD, left ventricular end-systolic diameter.

Note: Data are presented as median (interquartile range).

Table 4 Surgical procedure

	DN (331)	CB (177)	p	All (508)
Isolated CABG	77 (23.3%)	54 (30.5%)	0.076	131 (25.8%)
Any procedure with CABG	113 (34.1%)	68 (38.4%)	0.338	181 (35.6%)
One procedure (no CABG)- (valve/elective aneurysm)	46 (13.9%)	15 (8.5%)	0.073	62 (12.2%)
Two procedures (combination of valvular surgery, CABG, elective aneurysm, or double valvular)	116 (35.0%)	67 (37.8%)	0.530	183 (36.0%)
Three procedures (combination of valvular surgery, CABG, elective aneurysm, or multiple valvular)	65 (19.6%)	29 (16.4%)	0.369	94 (18.5%)
Four procedures (combination of valvular surgery, CABG, elective aneurysm, or multiple valvular)	27 (8.2%)	12 (6.8%)	0.579	39 (7.7%)
Cross-clamp duration (min)	61.5 (44.0–85.0)	63.0 (44.7–83.0)	0.577	63.0 (44.0–84.0)
ECT duration (min)	75.0 (60.7–95.0)	75.0 (59.0–100.0)	0.965	75.0 (60.0–97.0)
1 infusion	292 (88.2%)	15 (8.5%)	<0.0001	307 (60.4%)
2 infusions	39 (11.8%)	75 (42.4%)	<0.0001	114 (22.4%)
>2 infusions	0	87 (49.1%)	<0.0001	87 (17.1%)
Median infusion number	1.0 (1.0–1.0)	2.0 (2.0–3.0)	<0.0001	1.0 (1.0–2.0)

Abbreviations: CABG, coronary artery bypass grafting; CB, cold blood cardioplegia; DN, del Nido cardioplegia; ECT, extracorporeal circulation time.

Data are presented as number (percentage) and median (interquartile range).

Observations of the primary study endpoints revealed a negative relationship between preoperative hematocrit and postoperative troponin values in the entire cohort (p = 0.012) and the DN group (p = 0.004), as shown in [Fig. 1A]. However, this relationship was not apparent in the CB group, as indicated by the flat regression line (p = 0.674). Similar results were obtained when analyzing the relationship between hemoglobin and troponin (entire cohort: p = 0.004; DN group: p = 0.002; CB group: p = 0.509; [Fig. 1B]). Therefore, the lowest postoperative troponin values were estimated for the DN group with high preoperative hemoglobin and hematocrit, whereas the highest troponin values were estimated for the DN group with low preoperative hemoglobin and hematocrit ([Fig. 1A, B]).

Fig. 1 Relation between assessed determinants. (A) preoperative hematocrit; (B) preoperative hemoglobin; (C) preoperative white blood cell count; (D) preoperative platelet count and postoperative high-sensitivity troponin T (hs-TnT) release at 12 hours. CB, cold blood cardioplegia group; DN, del Nido group.

Furthermore, a positive relationship was found between preoperative white blood cell count and postoperative troponin release in the entire cohort and the DN and CB groups. However, this relationship was more pronounced in the CB group, as indicated by the steeper regression line (entire cohort: p < 0.001; DN group: p < 0.001; CB group: steeper regression line with p = 0.042; [Fig. 1C]). No relationship was found between preoperative platelet count and postoperative troponin release ([Fig. 1D]).

There was no relationship between the patient's age and postoperative troponin release ([Fig. 2A]). However, there was a significant relationship between preoperative creatinine, CCT, ECT, and postoperative troponin values in both groups and the entire cohort ([Fig. 2B–D]). No relationship was found between age, preoperative blood morphology parameters, creatinine, and the occurrence of a fall in EF. However, both extracorporeal circulation and CCT increased the risk of a fall in EF in a probit regression model ([Fig. 3]), which was more pronounced in the CB group.

Fig. 2 Relation between assessed determinants. (A) age; (B) preoperative creatinine; (C) cross-clamp time; (D) extracorporeal circulation time and postoperative high-sensitivity troponin T (hs-TnT) release at 12 hours. CB, cold blood cardioplegia group; DN, del Nido group.

Fig. 3 Cross-clamp time-related probability of decrease in ejection fraction of 5% or more (A) and extracorporeal circulation time-related probability of decrease in ejection fraction of 5% or more (B).

Postoperatively, more patients experienced a fall in EF in the CB group ([Table 5]). However, further secondary observations revealed no differences in mortality, myocardial infarction, stroke, MACCE, or the use of an IABP.

Table 5 Perioperative period

	DN (331)	CB (177)	p	All (508)
Mortality	15 (4.5%)	6 (3.4%)	0.538.	21 (4.1%)
Perioperative MI	12 (3.6%)	5 (2.8%)	0.633	17 (3.3%)
Perioperative IABP	18 (5.4%)	7 (3.9%)	0.462	25 (4.9%)
Stroke	4 (1.2%)	3 (1.7%)	0.654	7 (1.4%)
MACCE	25 (7.5%)	12 (6.7%)	0.749	37 (7.3%)
Fall in EF ≥ 5%	13 (3.9%)	21 (11.9%)	<0.001	34 (6.7%)
Hs-Troponin T at 12 hours (pg/mL)	581.4 (343.8–984.5)	556.3 (306.8–1345.0)	0.816	572.0 (336.0–1091.5)
Hs-Troponin T at 36 hours (pg/mL)	449.3 (231.0–1020.0)	546.0 (296.0–1275.0)	0.203	490.0 (251.0–1259.0)
Chest revision	20 (6.0%)	16 (9.0%)	0.210	36 (7.1%)
Perioperative AF (no previous arrhythmia)	31/253 (12.2%)	21/138 (15.2%)	0.376	52 (10.2%)
Delirium	12 (3.6%)	7 (3.9%)	0.852	19 (3.7%)
AKIN	96 (29.0%)	52 (29.4%)	0.929	148 (29.1%)
AKIN 1 (150–200% baseline creatinine)	57 (17.2%)	32 (18.1%)	0.808	89 (17.5%)
AKIN2 (200–300% baseline creatinine)	34 (10.3%)	18 (10.2%)	0.971	52 (10.2%)
AKIN3 (>300% baseline creatinine)	5 (1.5%)	2 (1.1%)	0.726	7 (1.4%)
CVVHDF	11 (3.3%)	7 (3.9%)	0.714	18 (3.5%)
Hospitalization time	6.0 (5.0- 8.0)	7.0 (6.0- 9.0)	<0.0001	7.0 (5.0- 9.0)

Abbreviations: AF, atrial fibrillation; AKIN, Acute Kidney Injury Network classification; CB, cold blood cardioplegia; CVVHDF, continuous venovenous hemodiafiltration; DN, del Nido cardioplegia; EF, ejection fraction; IABP, intra-aortic balloon pump; MACCE, major adverse cardiac and cerebrovascular events (mortality, myocardial infarction, stroke); MI, myocardial infarction.

Note: Data are presented as number (percentage) and median (interquartile range).

Discussion

Assessing the impact of determinants on the efficacy of cardioplegic solutions requires an adequate biomarker of ultrastructural damage. Although troponin T release cannot be considered a direct measure of myocardial injury, it is still the best biomarker that can reflect damage in a clinical setting.

The statistical analysis demonstrates that the same solution may have significantly different efficacy depending on other perioperative parameters. The relationship between hemoglobin, hematocrit, and troponin release at 12 hours appears to be the most demonstrative. As noted, del Nido patients with low preoperative hemoglobin and hematocrit represent a subgroup with the highest postoperative troponin release in the entire cohort, whereas del Nido patients with high preoperative hematocrit and hemoglobin represent the lowest troponin release in the entire cohort. Due to the significant blood additive (20% of infused volume), the DN is not a purely crystalloid solution. This contributes significantly to the solution's features, as blood provides superior oxygen delivery, and high buffering capacity, optimizes oncotic parameters, supplies free radical scavengers, and increases microcirculation blood flow.[9]

In contrast to patients who received crystalloid cardioplegia, using blood as a vehicle was associated with more operative stability and reduced postoperative morbidity.[1] Our study allows us to conclude that the positive effect of blood additives is apparent regardless of preoperative hematocrit when CB is used. It can be summarized that the blood cardioplegia solution has adequate hematocrit for satisfactory cardioprotection, regardless of the patient's blood morphology due to the 4:1 blood:crystalloid ratio. However, in a reversed ratio (1:4, as in DN), the hematocrit of the final solution may become insufficient in patients with low preoperative morphology parameters, which may impact the cardioprotective capacity of the cardioplegia, as reflected by significantly higher troponin release.

From other primary observations, we have noticed that the negative effect of high leukocyte values is apparent, regardless of the solution used, but it is much more pronounced in the CB group, possibly due to the higher volume of leukocyte-rich blood additive ([Fig. 1C]). Leukocyte depletion during cardiac surgery has previously been shown to prevent myocardial edema, decrease the incidence of ventricular arrhythmias, and reduce free-radical-mediated lung injury and cardiac reperfusion injury.[9] Some studies report on the effective use of leukocyte filtration.[10] [11]

Although this matter requires further investigation, it may be hypothesized that DN may be preferred in urgent cases with high preoperative leukocyte values due to inflammation or acute coronary syndrome.

We did not observe a relation between age and cardioprotection in our study, with regression curves being similar for both cardioplegia protocols. However, the literature describes the negative effect of advanced age on cardioprotection.[12] Furthermore, it has been reported that mitochondrial oxygen consumption significantly increases in mature and aged female hearts.[13] Aged hearts are generally vulnerable to ischemia–reperfusion injury.[12] [14] This matter certainly requires further investigation.

Unsurprisingly, both CCT and ECT affected the postoperative biomarker release and increased the probability of a fall in EF. Complex cardiac surgeries requiring long periods of aortic cross-clamping are associated with high rates of morbidity and mortality due to damage to the myocardium.[15] However, the fall in EF was more probable in the CB group ([Fig. 3A, B]), regardless of subsequent dosing. This leads to a recommendation to use DN when possibly long CCTs are considered. Although the number of patients with a significant fall in EF was greater in the CB group, a clear conclusion cannot be drawn due to possible divergences.

The lack of differences in mortality, myocardial infarction, stroke, and the need to use IABPs between groups must be noted from secondary observations. The efficacy of both solutions is satisfactory, but a comparative analysis regarding strong endpoints should be performed in a large, prospective study.

The impact of stenotic coronaries on cardioplegia efficacy should be discussed, as a trend for more frequent use of CB is visible in CABG cases. Homogeneous perfusion of all heart segments may be limited in poorly collateralized coronary artery stenosis cases when only aortic delivery is performed.[16] [17] [18] In such cases, subsequent dosing, as in the blood cardioplegia protocol, particularly when antegrade graft perfusion is available, provides appropriate cooling of the most ischemic zones and may improve the outcome.[19] [20] However, we did not notice any difference in favor of blood cardioplegia in our cohort, which is a similar finding to other reports on using the del Nido protocol in high-risk cases.[21] [22]

Study Limitations

This is a single-center, retrospective study, and the observation includes only the hospitalization period. The sample is heterogeneous (it would not be possible to correct this without reducing the sample size considerably, leaving the analysis underpowered for the main endpoints of interest). However, no statistical differences are present at baseline and intraoperatively. No matching was performed for the comparative analysis of the DN and CB groups, as the comparison was not an aim of the study.

Conclusion

Depending on the clinical scenario, multiple factors affect cardioprotection, and specific cardioplegia may be beneficial. Cardioprotection with CB may be more beneficial in anemic patients while using DN may benefit patients with high preoperative leukocyte values and expected long CCTs. Further prospective studies are needed.

Conflict of Interest

None declared.

Data Availability Statement

The article's data can be shared on reasonable request to the corresponding author.

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Publication History

Received: 14 February 2023

Accepted: 25 July 2023

Accepted Manuscript online:
26 July 2023

Article published online:
29 August 2023