Clin Chem. 2004 Jun 24   [Epub ahead of print] 

Cardiac Troponin T for Prediction of Short- and Long-Term Morbidity and
Mortality after Elective Open Heart Surgery.

Lehrke S, Steen H, Sievers HH, Peters H, Opitz A, Muller-Bardorff M, Wiegand UK,
Katus HA, Giannitsis E.

Johns Hopkins University, Department of Cardiology, Baltimore, MD.

BACKGROUND: Increased cardiac troponins in blood are observed after virtually
every open heart surgery, indicating perioperative myocardial cell injury. We
sought to determine the optimum time point for blood sampling and the respective
cutoff value of cardiac troponin T (cTnT) for risk assessment in patients
undergoing cardiac surgery. METHODS: In a series of 204 patients undergoing
scheduled open heart surgery, mainly for coronary artery bypass grafting (n =
132) or valve repair (n = 27), cTnT concentrations were measured before and 4
and 8 h after cross-clamping and then daily for 7 days. Individual risk was
assessed by use of the Cleveland Clinic Foundation Risk score and intraoperative
risk indicators such as duration of cardiopulmonary bypass, cross-clamping, and
perioperative release of cardiac markers. Patients were followed for 28 months.
RESULTS: Cardiac mortality, all-cause mortality rates, and rates of nonfatal
acute myocardial infarction (AMI) at 28 months were 6.9%, 8.8%, and 6.8%,
respectively. cTnT was higher in patients with Q-wave AMI or postoperative heart
failure requiring inotropic support, and in nonsurvivors. The ROC curve revealed
a cTnT >/=0.46 micro g/L at 48 h as the optimum discriminator for long-term
cardiac mortality. Stepwise logistic regression identified higher Cleveland
Clinic Risk Score [odds ratio (OR) = 2.6 per point, cross-clamp time >65 min (OR
= 6.6), and cTnT (OR = 4.9) as significant and independent predictors of
long-term cardiac mortality. CONCLUSIONS: A single postoperative cTnT
measurement can be used to estimate myocardial cell injury that impacts
long-term survival after open heart surgery. It adds independently to
established risk indicators.

Thorac Cardiovasc Surg.  2004 Jun;52(3):141-6.  

Correction of congenital heart defects in Jehovah's witness children.

Alexi-Meskishvili V, Stiller B, Koster A, Bottcher W, Hubler M, Photiadis J,
Lange PE, Hetzer R.

Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin,
Berlin, Germany. alexi@dhzb.de

Between August 1989 and July 2003 14 Jehovah's Witness children with congenital
heart defects (CHD) aged under 14 years (median 2.9 years) and with a median
weight of 14 kg underwent 16 operations with cardiopulmonary bypass (CPB). Five
children had been operated on previously between one to three times.
Preoperatively, 7 children were prepared with oral iron supplementation and 10
received erythropoietin. Mean hemoglobin (Hb) at admission was 14.4 g/dl (range
10.9 - 19.2). The cardiopulmonary bypass (CPB) circuit was modified to reduce
total priming volume. High doses of aprotinin were administered. The modified
ultrafiltration (MUF) circuit, used in 7 patients, was parallel to the ECC
circuit with continuous circulation of the blood through a small shunt between
the arterial and venous lines. Operations performed consisted of VSD closure (3
pts.), ASD closure (3 pts.), Fontan operation (2 pts.), and complete AV canal
correction, aortic commissurotomy, Ross operation, Glenn shunt, cor triatriatum
correction, MV reconstruction combined with left outflow tract stenosis
resection, correction of absent pulmonary valve syndrome, and correction of
tetralogy of Fallot in one patient each. There were no deaths. Mean duration of
CPB was 192 min and mean aortic cross-clamp time 40 min. The Hb value at the end
of the operation was 4.9 - 14.5 g/dl (mean 9.6) and at discharge it was 7.1 -
14.5 g/dl (mean 15.5). No blood or blood products were used in any patient.
CONCLUSION: Bloodless cardiac surgery with and without CPB can be safely
performed in Jehovah's Witness infants and children.

Chest.  2004 Jun;125(6):2196-205.  

Neurological complications after coronary artery bypass grafting related to the
performance of cardiopulmonary bypass.

Ganushchak YM, Fransen EJ, Visser C, De Jong DS, Maessen JG.

Department of Extra-Corporeal Circulation, University Hospital Maastricht,
Maastricht, The Netherlands. yga@scpc.azm.nl

STUDY OBJECTIVES: Neurologic disorders belong among the most serious
complications of cardiac surgery. We tested the hypothesis that combinations of
hemodynamic events from apparently normal cardiopulmonary bypass (CPB)
procedures are related to the development of postoperative neurologic
complications and affect the impact of common clinical risk factors. DESIGN:
Retrospective study. SETTING: Cardiothoracic surgery department in a university
hospital. METHODS AND PATIENTS: A multivariate statistical procedure (ie,
cluster analysis) was applied to a data set of automatically recorded perfusions
from 1,395 patients who had undergone coronary artery bypass grafting. One-way
analysis of variance was used to select five parameters with the strongest
significant correlation to postoperative neurologic complications for further
cluster analysis. The dependencies in the clusters were tested against common
clinical risk factors. To our knowledge, this is the first study of its kind.
RESULTS: The following five parameters emerged for cluster analysis: mean
arterial pressure (MAP); dispersion of MAP; dispersion of systemic vascular
resistance; dispersion of arterial pulse pressure; and the maximum value of
mixed venous saturation. Using these parameters, we found four clusters that
were significantly different by CPB performance (first cluster, 389 patients;
second cluster, 431 patients; third cluster; and fourth cluster, 229 patients).
The frequency of postoperative neurologic complications was 0.3% in the first
cluster and increased to 3.9% in the fourth cluster. Importantly, the impact of
common clinical risk factors for postoperative neurologic complications was
affected by the performance of the CPB procedure. For example, the frequency of
neurologic complications among patients with cerebrovascular disease in their
medical history was 22% in the fourth cluster, whereas it was zero in the second
cluster. CONCLUSIONS: This study shows that apparently normal CPB procedures
affect the impact of common clinical risk factors on postoperative neurologic
complications. Patients who underwent CPB procedures with large fluctuations in
hemodynamic parameters particularly showed an increased risk for the development
of postoperative neurologic complications.

J Thorac Cardiovasc Surg.  2004 Jun;127(6):1728-34.  

The effect of maternal hypothermic cardiopulmonary bypass on fetal lamb
temperature, hemodynamics, oxygenation, and acid-base balance.

Pardi G, Ferrari MM, Iorio F, Acocella F, Boero V, Berlanda N, Monaco A, Reato
C, Santoro F, Cetin I.

Department of Obstetrics and Gynecology, San Paolo Hospital, Milan, Italy.
Giorgio.Pardi@unimi.it

OBJECTIVE: To evaluate fetal-maternal temperature relationship and fetal
cardiovascular and metabolic response during maternal hypothermic
cardiopulmonary bypass in pregnant ewes. METHODS: Cardiopulmonary bypass was
instituted in 9 pregnant ewes, reaching 2 different levels of maternal
hypothermia: 24 degrees C to 20 degrees C (deep hypothermia) in group A (5
cases) and less than 20 degrees C (very deep hypothermia) in group B (4 cases).
Hypothermic levels were maintained for 20 minutes, then the rewarming phase was
started. Fetal and maternal temperature, blood pressure, heart rate,
electrocardiogram, blood gases, and acid-base balance were evaluated at
different levels of hypothermia and during recovery. RESULTS: Fetal survival was
related to maternal hypothermia: all group A fetuses survived, while 2 of 4
fetuses of group B in which maternal temperature was lowered below 18 degrees C
died in a very deep acidotic and hypoxic status. Maternal temperature was always
lower than fetal temperature during cooling; during rewarming the gradient was
inverted. The start of cardiopulmonary bypass and cooling was associated with
transient fetal tachycardia and hypertension; then, both fetal heart rate and
blood pressure progressively decreased. The reduction of fetal heart rate was of
7 beats per minute for each degree of fetal cooling. Deep maternal hypothermia
was associated with fetal alkalosis and reduction of Po(2). Very deep
hypothermia, in particular below 18 degrees C, caused irreversible fetal
acidosis and hypoxia. CONCLUSIONS: Deep maternal hypothermic cardiopulmonary
bypass was associated with reversible modifications in fetal cardiovascular
parameters, blood gases, and acid-base balance and therefore with fetal
survival. On the contrary, fetuses did not survive to a very deep hypothermia
below 18 degrees C.

 Ann Thorac Surg.  2004 Jun;77(6):2138-43.  

Comparison of low-flow cardiopulmonary bypass and circulatory arrest on brain
oxygen and metabolism.

Schultz S, Creed J, Schears G, Zaitseva T, Greeley W, Wilson DF, Pastuszko A.

Department of Anesthesiology and Critical Care, Children's Hospital of
Philadelphia, Philadelphia, Pennsylvania, USA.

BACKGROUND: In the neonatal brain we measured oxygen (Bo(2)), extracellular
striatal dopamine (DA), and striatal tissue levels of ortho-tyrosine (o-tyr)
during low-flow cardiopulmonary bypass (LFCPB) or deep hypothermic circulatory
arrest (DHCA) and the post-bypass recovery period. METHODS: Newborn piglets were
assigned to sham (n = 6), LFCPB (n = 8), or DHCA (n = 6) groups. Animals were
cooled to 18 degrees C and underwent DHCA or LFCPB (20 mL x kg(-1) x min(-1))
for 90 minutes. The Bo(2) was measured by quenching the phosphorescence, DA by
microdialysis, and hydroxyl radicals by o-tyr levels. The results are presented
as the mean +/- SD (p < 0.05 was significant). RESULTS: Baseline Bo(2) was
between 45 to 60 mm Hg. At the end of LFCPB, Bo(2) was 10.5 +/- 1.2 mm Hg. By 5
and 30 minutes of arrest during DHCA, Bo(2) fell to 4.2 +/- 2.5 mm Hg and 1.4
+/- 0.7 mm Hg, respectively. Compared with control, extracellular DA did not
change during LFCPB. During DHCA extracellular levels of DA increased, by
750-fold from baseline at 45 minutes and to a maximum of 53000-fold at 75
minutes. After 2 hours of recovery from DHCA, the o-tyr within the striatum
increased about sixfold as compared with control. There was no change in o-tyr
measured after LFCPB. CONCLUSIONS: In DHCA, but not LFCPB, levels of DA and
o-tyr increased considerably in the striatum of piglets, a finding that may
indicate the exhaustion of cellular energy levels and contribute substantially
to cellular injury.

J Thorac Cardiovasc Surg.  2004 Jun;127(6):1697-702.  

Evaluation of heart fatty acid-binding protein as a rapid indicator for
assessment of myocardial damage in pediatric cardiac surgery.

Hasegawa T, Yoshimura N, Oka S, Ootaki Y, Toyoda Y, Yamaguchi M.

Department of Cardiothoracic Surgery, Kobe Children's Hospital, Kobe, Japan.

OBJECTIVES: Perioperative myocardial damage is a major determinant of
postoperative cardiac dysfunction for congenital heart disease. Heart fatty
acid-binding protein is reported to be a rapid marker of perioperative
myocardial damage that peaks earlier than creatine kinase isoenzyme MB or
cardiac troponin T in adults. The objective of this study was to assess the
suitability of using serum concentrations of heart fatty acid-binding protein
for evaluation of perioperative myocardial damage in pediatric cardiac surgery.
METHODS: After institutional review board approval and informed consent, 100
children undergoing open procedures for congenital heart disease were
prospectively enrolled in the study. Mean age at operation was 4.9 +/- 0.4
years. Serum concentrations of heart fatty acid-binding protein, creatine kinase
isoenzyme MB, and cardiac troponin T were measured serially before operation and
at 0, 1, 2, 3, and 6 hours after aortic declamping. Relationships between serum
peak level of heart fatty acid-binding protein and intraoperative and
postoperative clinical variables were evaluated. RESULTS: Serum heart fatty
acid-binding protein reached its peak level at 1 hour after declamping in 95
patients (95%), which was significantly earlier (P <.01) than serum creatine
kinase isoenzyme MB or cardiac troponin T. In addition, serum heart fatty
acid-binding protein level immediately after declamping correlated strongly with
serum peak heart fatty acid-binding protein level (r = 0.91, P <.01). The serum
peak level of heart fatty acid-binding protein correlated with those of creatine
kinase isoenzyme MB (r = 0.77, P <.01) and cardiac troponin T (r = 0.80, P
<.01). In the forward stepwise multiple regression analysis, age (P <.0001),
aortic crossclamp time (P <.0001), the presence of a ventriculotomy (P <.001),
and the lowest hematocrit level during cardiopulmonary bypass (P <.05) were
significant intraoperative variables that influenced the release of heart fatty
acid-binding protein. There were significant relationships between serum peak
heart fatty acid-binding protein level and postoperative inotropic support,
duration of intubation, and intensive care unit stay (P <.01 for each).
CONCLUSIONS: Heart fatty acid-binding protein is a rapid marker for assessment
of myocardial damage and clinical outcome in pediatric cardiac surgery. In
particular, serum heart fatty acid-binding protein level immediately after
aortic declamping may be a potentially useful prognostic indicator of myocardial
damage as well as clinical outcome in pediatric cardiac surgery.

Anesthesiology.  2004 Jun;100(6):1387-93.  

Evidence for development of capillary leak syndrome associated with
cardiopulmonary bypass in pediatric patients with the homozygous C4A null
phenotype.

Zhang S, Wang S, Yao S.

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong
University of Science and Technology, Wuhan, China. zhangshh@public.wh.hb.cn

BACKGROUND: The mechanism of postoperative capillary leak syndrome related to
cardiopulmonary bypass (CPB) is unknown. The authors hypothesized that C4 gene
polymorphism might be involved in the development of the syndrome because
complement activation is associated with CPB and protamine administration, and
the two isotypes of C4 (C4A and C4B) differ in their biochemical and functional
properties after activation. METHODS: One hundred fifty-six pediatric patients
referred for elective cardiac surgery with CPB were included in the study. C4
isotype studies were performed in plasma samples obtained before surgery, with
use of agarose gel immunofixation and crossed immunoelectrophoresis. Five
possible C4 phenotype groups were observed, which were abbreviated as follows:
(1) AABB = no detectable null alleles, (2) A0BB = a single null allele
(heterozygous) at the C4A locus, (3) 00BB = a homozygous C4A null allele, (4)
AAB0 = a single null allele (heterozygous) at the C4B locus, and (5) AA00 = a
homozygous C4B null allele. The patients were classified into five groups
according to their C4 phenotypes. Before CPB and at 1 h after CPB, plasma
protein was measured with a biuret test kit. Plasma colloid osmotic pressure was
determined with a membrane osmometer. Evans blue dye was used to measure plasma
volume, serum protein, intravenous protein pool, and transvascular escape rate
of Evans blue dye. RESULTS: Of 156 pediatric patients enrolled, 80 were assigned
to the AABB group, 28 were assigned to the A0BB group, 7 were assigned to the
00BB group, 31 were assigned to the AAB0 group, and 10 were assigned to the AA00
group, according to their C4 phenotypes. At 1 h after CPB, serum protein
concentrations averaged 3.6 +/- 0.4 g/dl in patients with the 00BB C4 phenotype;
this value was significantly lower (P < 0.01) than that in patients with other
C4 phenotypes. The changes of intravenous protein pool and colloid osmotic
pressure were comparable with the change in serum protein concentration. At 1 h
after CPB, the transvascular escape rate of Evans blue dye averaged 11.5 +/-
1.3%/h in patients with the 00BB C4 phenotype; this value was significantly
higher (P < 0.01) than that in patients with other C4 phenotypes. CONCLUSIONS:
In this study, capillary leak syndrome induced by CPB occurred only in patients
with the homozygous C4A null phenotype.

Anesthesiology.  2004 Jun;100(6):1345-52.  

Comment in:
    Anesthesiology. 2004 Jun;100(6):1339-41.

Intraoperative hyperglycemia during infant cardiac surgery is not associated with
adverse neurodevelopmental outcomes at 1, 4, and 8 years.

de Ferranti S, Gauvreau K, Hickey PR, Jonas RA, Wypij D, du Plessis A, Bellinger
DC, Kuban K, Newburger JW, Laussen PC.

Children's Hospital, Boston, Massachusetts 02115, USA.

BACKGROUND: It is unknown whether intraoperative hyperglycemia in infants is
associated with worse neurodevelopmental outcomes after low-flow cardiopulmonary
bypass (LF), deep hypothermic circulatory arrest (CA), or both. METHODS: In a
database review of a prospective trial of 171 infants undergoing arterial switch
for D-transposition of the great arteries who were randomly assigned to
predominantly LF or CA, glucose was measured after induction (T1), 5 min after
cardiopulmonary bypass onset (T2), at the onset of CA or LF (T3), 5 min after
CPB resumption (T4), at rewarming to 32 degrees C (T5), 10 min after
cardiopulmonary bypass weaning (T6), and 90 min after CA or LF (T7). Outcomes
included seizures, electroencephalographic findings, and neurodevelopmental
evaluation at 1, 4, and 8 yr. RESULTS: Glucose concentrations were affected by
support strategy and age at surgery. Lower glucose in the entire group at T6-T7
tended to predict electroencephalographic seizures (P = 0.06 and P = 0.007) but
was not related to clinical seizures. Within the predominantly CA group, higher
glucose did not correlate with worse outcomes. Rather, it was associated with
more rapid electroencephalographic normalization of "close burst" and "relative
continuous" activity at all times except T2 (P < or = 0.03), a finding more
pronounced in infants aged 7 days old or younger. Intraoperative serum glucose
concentrations were unrelated to neurodevelopmental outcomes at ages 1, 4, and 8
yr. CONCLUSIONS: Low glucose after cardiopulmonary bypass tended to relate to
electroencephalographic seizures and slower electroencephalogram recovery,
independent of CA duration. High glucose concentrations were not associated with
worse neurodevelopmental outcomes. Avoiding hypoglycemia may be preferable to
restricting glucose in infants undergoing heart surgery.

Anesth Analg.  2004 Jun;98(6):1586-94, table of contents.  

The impact of heparin-coated cardiopulmonary bypass circuits on pulmonary
function and the release of inflammatory mediators.

de Vroege R, van Oeveren W, van Klarenbosch J, Stooker W, Huybregts MA, Hack CE,
van Barneveld L, Eijsman L, Wildevuur CR.

Departments of Extracorporeal Circulation, Room 6A 149, Vrije Universiteit
Medisch Centrum, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
r.devroege@azvu.nl

Reduction of the inflammatory reaction with the use of heparin coating has been
found during and after cardiopulmonary bypass (CPB). The question remains
whether this reduced reaction also decreases the magnitude of CPB-induced
pulmonary dysfunction. We therefore evaluated the effects of a heparin-coated
circuit versus a similar uncoated circuit on pulmonary indices as well as on
inflammatory markers of complement activation (C3b/c),
elastase-alpha(1)-antitrypsin complex, and secretory phospholipase A(2)
(sPLA(2)) during and after CPB. Fifty-one patients were randomly assigned into
two groups undergoing coronary artery bypass grafting with either a
heparin-coated (Group 1) or an uncoated (Group 2) circuit. During CPB, a
continuous positive airway pressure of 5 cm H(2)O and a fraction of inspired
oxygen (FIO(2)) of 0.21 were maintained. Differences in favor of the coated
circuit were found in pulmonary shunt fraction (P < 0.05), pulmonary vascular
resistance index (P < 0.05), and PaO(2)/FIO(2) ratio (P < 0.05) after CPB and in
the intensive care unit. During and after CPB, the coated group demonstrated
lower levels of sPLA(2). After CPB, C3b/c and the elastase-alpha(1)-antitrypsin
complex were significantly less in the coated group (P < 0.001). The coated
circuit was associated with a reduced inflammatory response, decreased pulmonary
vascular resistance index and pulmonary shunt fraction, and increased
PaO(2)/FIO(2) ratio, suggesting that the coated circuit may have beneficial
effects on pulmonary function. The correlation with sPLA(2), leukocyte
activation, and postoperative leukocyte count suggests reduced activation of
pulmonary capillary endothelial cells. IMPLICATIONS: Heparin coating of the
extracorporeal circuit reduces the inflammatory response during cardiopulmonary
bypass. Analysis of indices of pulmonary function indicates that use of heparin
coating may result in less impaired gas exchange.