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.
