Intensive Care Med. 2008 May 31. [Epub ahead of print]

Plasma angiopoietin-2 levels increase in children following cardiopulmonary
bypass.

Giuliano JS Jr, Lahni PM, Bigham MT, Manning PB, Nelson DP, Wong HR, Wheeler DS.

Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical
Center, 3333 Burnet Avenue, Cincinnati, OH, 45229-3039, USA.

OBJECTIVE: The aim was to investigate the effects of cardiopulmonary bypass (CPB)
on plasma levels of the vascular growth factors, angiopoietin (angpt)-1, angpt-2,
and vascular endothelial growth factor (VEGF). DESIGN: The design was a
prospective, clinical investigation. SETTING: The setting was a 12-bed pediatric 
cardiac intensive care unit of a tertiary children's medical center. PATIENTS:
The patients were 48 children (median age, 5 months) undergoing surgical
correction or palliation of congenital heart disease who were prospectively
enrolled following informed consent. INTERVENTIONS: There were no interventions
in this study. MEASUREMENTS AND RESULTS: Plasma samples were obtained at baseline
and at 0, 6, and 24 h following CPB. Angpt-1, angpt-2, and VEGF levels were
measured via commercial ELISA. Angpt-2 levels increased by 6 h (0.95, IQR
0.43-2.08 ng mL(-1) vs. 4.62, IQR 1.16-6.93 ng mL(-1), P < 0.05) and remained
significantly elevated at 24 h after CPB (1.85, IQR 0.70-2.76 ng mL(-1); P <
0.05). Angpt-1 levels remained unchanged immediately after CPB, but were
significantly decreased at 24 h after CPB (0.64, IQR 0.40-1.62 ng mL(-1) vs.
1.99, IQR 1.23-2.63 ng mL(-1), P < 0.05). Angpt-2 levels correlated significantly
with cardiac intensive care unit (CICU) length of stay (LOS) and were an
independent predictor for CICU LOS on subsequent multivariate analysis.
CONCLUSIONS: Angpt-2 appears to be an important biomarker of adverse outcome
following CPB in children.

Magy Seb. 2008 May;61:17-21.

[Pregnancy and cardiac surgery with cardiopulmonary bypass.]

[Article in Hungarian]

Aranyosi J Jr, Aranyosi J, Péterffy A.

Debreceni Egyetem, Orvos- és Egészségtudományi Centrum Szülészeti és
Nogyógyászati Klinika 4012 Debrecen Pf. 37.

Heart disease during pregnancy necessitating cardiac surgery is potentially
increasing maternal and fetal morbidity and mortality. Most patients know about
their heart disease long before conception however the relation between the
deteriorating cardiac function and the perinatal complications is not emphasized.
Best possible results can be achieved by providing preconceptional counseling for
the cardiopathic patients. Consequently, heart-surgery can be performed before
pregnancy thereby the maternal risk is lower and the fetal loss or induced
abortion can be avoided. The pregnant state is not optimal for cardiac surgery as
the principle interest of the mother and the fetus is different. Cardiac surgery 
should be reserved only for saving the patient's life when medical therapy proves
insufficient or when the expectative management leads to acute heart failure. The
multidisciplinary approach, correct risk assessment, diagnosis, operative
indication, timing along with appropriate anaesthesia, extracorporeal circulation
and alert monitoring of the uterine activity and fetal heart rate patterns make
the intervention technically safe. Fetal monitoring is inevitable for prompt
correction of operative conditions in case of impending hypoxemia. The
perioperative fetal risk can be reduced by applying normothermia, high mean
arterial pressure and cardiac index during the intentionally shortest
intervention. Cardiac operation with cardiopulmonary bypass during pregnancy has 
become a relatively safe procedure for the mother but not for the baby.

ASAIO J. 2008 May-Jun;54(3):306-15.

A performance evaluation of eight geometrically different 10 Fr pediatric
arterial cannulae under pulsatile and nonpulsatile perfusion conditions in an
infant cardiopulmonary bypass model.

Rider AR, Ji B, Kunselman AR, Weiss WJ, Myers JL, Undar A.

Department of Pediatrics, Penn State Milton S. Hershey Medical Center, Penn State
College Medicine, Penn State Children's Hospital, Hershey, Pennsylvania
17033-0850, USA.

This investigation compared pressure drops and surplus hemodynamic energy (SHE)
levels in eight commercially available pediatric aortic cannulae (10 Fr) with
different geometries during pulsatile and nonpulsatile perfusion conditions in an
in vitro infant model of cardiopulmonary bypass. For each trial, the cannula was 
placed at the distal end of the arterial line, and the insertion tip was fixed to
the inlet of the simulated patient. The pseudo patient was subjected to seven
pump flow rates ranging from 400 to 1000 ml/min (at 100 ml/min increments), and
the mean arterial pressure was set at a constant 40 mm Hg via Hoffman clamp. Of
the eight cannulae, the Surgimedics and THI models had significantly larger
pressure drops (48.8 +/- 0.3 mm Hg and 48.3 +/- 1.4 mm Hg, respectively; 600
ml/min pulsatile) compared with the RMI cannula (27.6 +/- 1.2 mm Hg; 600 ml/min
pulsatile), which created, on average, half of the pressure drop seen in the
poorest performing cannulae. When perfusion mode was switched from nonpulsatile
to pulsatile, there was a 7-9 fold increase in delivery of SHE recorded at both
the pre- and postcannulae sites, regardless of which cannula was being tested.
Despite being classified under the same size (10 Fr), these eight cannulae were
found to vary considerably in length, inner diameter, and geometrical design. The
results suggest that these differences can have a significant impact on pressure 
drops, as well as generation and delivery of SHE. Furthermore, it was found that 
pulsatile perfusion produced more "extra" hemodynamic energy when compared with
nonpulsatile perfusion, regardless of cannula model.

Ann Neurol. 2008 May;63(5):581-90.

Cognition 6 years after surgical or medical therapy for coronary artery disease.

Selnes OA, Grega MA, Bailey MM, Pham LD, Zeger SL, Baumgartner WA, McKhann GM.

Department of Neurology, Baltimore, MD 21205-1910, USA. oselnes@jhmi.edu

OBJECTIVE: The choice of coronary artery bypass grafting (CABG) as an
intervention for coronary artery disease has been clouded by concerns about
postoperative cognitive decline. Long-term cognitive decline after CABG has been 
reported, but without appropriate control subjects, it is not known whether this 
decline is specific to CABG or related to other factors such as cerebrovascular
disease. METHODS: This prospective, observational study of patients with
diagnosed coronary artery disease included 152 CABG and 92 nonsurgical cardiac
comparison patients from one institution. The main outcome measure was
within-patient change in cognitive performance for eight cognitive domains from
baseline to 12- and 72-month follow-up. RESULTS: Mild late cognitive decline was 
observed for both study groups, but despite greater than 80% power to detect a
0.2 standard deviation difference, there were no statistically significant
differences between the surgical and nonsurgical patients in the degree of change
from 12 to 72 months for any cognitive domain. There was also no difference
between groups in the degree of change from baseline to 72 months or in the
number of patients with a Mini-Mental State Examination score in the clinically
impaired range at 72 months. INTERPRETATION: Late cognitive decline does occur in
patients who have undergone CABG surgery, but the degree of this decline does not
differ from that observed in patients of similar age with coronary artery disease
who have not undergone CABG. Therefore, late cognitive decline after CABG is not 
specific to the use of cardiopulmonary bypass.

Am J Cardiol. 2008 May 15;101(10):1472-8. Epub 2008 Mar 17.

Incidence, imaging analysis, and early and late outcomes of stroke after cardiac 
valve operation.

Filsoufi F, Rahmanian PB, Castillo JG, Bronster D, Adams DH.

Department of Cardiothoracic Surgery, Mount Sinai School of Medicine, New York,
New York, USA. farzan@filfoufi@mountinai.org

The aim of this study was to analyze the incidence, topography, and mechanisms of
stroke, independent predictors, and late outcome after cardiac valve operations. 
We retrospectively analyzed prospectively collected data from 2,808 patients
(mean age 63 +/- 15 years, n = 1,610, 55% men) who underwent valve surgery with
or without concomitant coronary artery bypass grafting from January 1998 to
December 2006. Stroke was defined as any new permanent focal neurologic deficit. 
Overall incidence of stroke was 2.2% (n = 63) and decreased during the study
period from 3.3% (1998 to 2002) to 1.3% (2003 to 2006; p = 0.001). The highest
stroke rate was observed after double aortic/mitral valve replacement (5.4%) and 
valve/coronary artery bypass grafting procedures (3.6%). Brain imaging was
positive in 74% (n = 43 of 58) and showed ischemic stroke in all patients and
hemorrhagic conversion in 28%. Distribution of acute stroke was large territory
embolic artery (n = 33, 77%), watershed (n = 7, 16%), and mixed pattern (n = 3,
7%). Multivariate analysis revealed calcified ascending aorta (odds ratio [OR]
2.7), female gender (OR 2.6), ejection fraction <30% (OR 2.3), diabetes (OR 2.2),
age >70 years (OR 2.0), and cardiopulmonary bypass time >120 minutes (OR 3.7) as 
predictors of stroke. Hospital mortality was 24% and 4.6% in patients with and
without stroke, respectively. Survival of stroke patients was 78% and 54% at 1
year and 5 years, respectively, and was significantly decreased compared with
patients without stroke. Valve pathology including endocarditis did not influence
the incidence of stroke. Intraoperative epiaortic scanning may contribute in
decreasing the incidence of this complication and may be warranted in all
patients undergoing valvular surgery. In conclusion, stroke after valvular
surgery is associated with an increased hospital mortality and morbidity and
decreased long-term survival.

 Eur J Anaesthesiol. 2008 May 9:1-8. [Epub ahead of print]

Association of N-terminal pro-brain natriuretic peptide and cardiac troponin T
with in-hospital cardiac events in elderly patients undergoing coronary artery
surgery.

Suttner S, Boldt J, Lang K, Röhm KD, Piper SN, Mayer J.

Klinikum der Stadt Ludwigshafen, Department of Anaesthesiology and Intensive Care
Medicine, Ludwigshafen, Germany.

SummaryBackground and objectivesDespite evidence of their prognostic power for
non-surgical patients, the value of perioperative natriuretic peptides and
cardiac troponins as markers of cardiac events is incompletely defined. This
study sought to examine whether perioperative N-terminal pro-brain natriuretic
peptide (NT-proBNP) and cardiac troponin T (cTnT) levels could be used for the
prediction of in-hospital cardiac events in elderly patients undergoing elective 
coronary artery bypass grafting. METHODS: Ninety-eight elderly patients (>75 yr) 
undergoing elective coronary artery bypass grafting with cardiopulmonary bypass
were enrolled and followed up for 12-15 months. NT-proBNP and cTnT levels were
measured before induction of anaesthesia and 12, 24 and 48 h after surgery. To
identify the best discriminatory level of NT-proBNP and cTnT receiver operating
characteristics curves were analysed. RESULTS: Thirty-four patients experienced
54 in-hospital cardiac events. Patients with complications had significantly
higher NT-proBNP and cTnT levels than those without complications. Receiver
operating characteristics curve analysis revealed cut-off levels of 2361 pg mL-1 
and 0.66 mug mL-1 for NT-proBNP and cTnT (sensitivity, specificity, positive
predictive value and negative predictive value of 84.3%, 89.4%, 78.9% and 92.4%, 
and 93.7%, 74.2%, 63.8% and 96.1%, respectively) at 24 h after surgery to be
associated with in-hospital cardiac events. An elevation of both biomarkers above
these threshold values was independently associated with individual postoperative
complications (odds ratio, 18.9; 95%, CI, 2.3-106.1). CONCLUSIONS: In elderly
patients undergoing elective coronary artery bypass grafting surgery, high values
of NT-proBNP and cTnT measured 24 h after the end of surgery were independently
associated with in-hospital cardiac events.

J Card Surg. 2008 May 7. [Epub ahead of print]

Antegrade Versus Retrograde Cerebral Perfusion in Relation to Postoperative
Complications Following Aortic Arch Surgery for Acute Aortic Dissection Type A.

Apostolakis E, Koletsis EN, Dedeilias P, Kokotsakis JN, Sakellaropoulos G, Psevdi
A, Bolos K, Dougenis D.

Cardiothoracic Surgery Department, School of Medicine, University of Patras,
Greece.

Background: Aortic arch surgery is impossible without the temporary interruption 
of brain perfusion and therefore is associated with high incidence of neurologic 
injury. The deep hypothermic circulatory arrest (HCA), in combination with
antegrade or retrograde cerebral perfusion (RCP), is a well-established method of
brain protection in aortic arch surgery. In this retrospective study, we compare 
the two methods of brain perfusion. Materials and Methods: From 1998 to 2006, 48 
consecutive patients were urgently operated for acute type A aortic dissection
and underwent arch replacement under deep hypothermic circulatory arrest (DHCA). 
All distal anastomoses were performed with open aorta, and the arch was replaced 
totally in 15 cases and partially in the remaining 33 cases. Our patient cohort
is divided into those protected with antegrade cerebral perfusion (ACP) (group A,
n = 23) and those protected with RCP (group B, n = 25). Results: No significant
difference was found between groups A and B with respect to cardiopulmonary
bypass-time, brain-ischemia time, cerebral-perfusion time, permanent neurologic
dysfunction, and mortality. The incidence of temporary neurologic dysfunction was
16.0% for group A and 43.50% for group B (p = 0.04). The mean extubation time was
3.39 +/- 1.40 days for group A and 4.96 +/- 1.83 days for group B (p = 0.0018).
The mean ICU-stay was 4.4 +/- 2.3 days for group A and 6.9 +/- 2.84 days for
group B (p = 0.0017). The hospital-stay was 14.38 +/- 4.06 days for group A and
19.65 +/- 6.91 days for group B (p = 0.0026). Conclusion: The antegrade perfusion
seems to be related with significantly lower incidence of temporary neurological 
complications, earlier extubation, shorter ICU-stay, and hospitalization, and
hence lower total cost.

Brain Res. 2008 Jun 5;1213:1-11. Epub 2008 Apr 1.

Biomarker evidence for mild central nervous system injury after
surgically-induced circulation arrest.

Siman R, Roberts VL, McNeil E, Dang A, Bavaria JE, Ramchandren S, McGarvey M.

Department of Neurosurgery, University of Pennsylvania School of Medicine,
Philadelphia, PA 19104, USA; Center for Brain Injury and Repair, University of
Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Previously, we identified 14-3-3 beta and zeta isoforms and proteolytic fragments
of alpha-spectrin as proteins released from degenerating neurons that also rise
markedly in cerebrospinal fluid (CSF) following experimental brain injury or
ischemia in rodents, but these proteins have not been studied before as potential
biomarkers for ischemic central nervous system injury in humans. Here we describe
longitudinal analysis of these proteins along with the neuron-enriched
hypophosphorylated neurofilament H (pNFH) and the deubiquitinating enzyme UCH-L1 
in lumbar CSF samples from 19 surgical cases of aortic aneurysm repair, 7
involving cardiopulmonary bypass with deep hypothermic circulatory arrest (DHCA).
CSF levels of the proteins were near the lower limit of detection by Western blot
or enzyme-linked fluorescence immunoassay at the onset of surgical procedures,
but increased substantially in a subset of cases, typically within 12-24 h. All
cases involving DHCA were characterized by >3-fold elevations in CSF levels of
the two 14-3-3 isoforms, UCH-L1, and pNFH. Six of 7 also exhibited marked
increases in alpha-spectrin fragments generated by calpain, a protease known to
trigger necrotic neurodegeneration. Among cases involving aortic cross-clamping
but not DHCA, the proteins rose in CSF preferentially in the subset experiencing 
acute neurological complications. Our results suggest the neuron-enriched
14-3-3beta, 14-3-3zeta, pNFH, UCH-L1, and calpain-cleaved alpha-spectrin may
serve as a panel of biomarkers with clinical potential for the detection and
management of ischemic central nervous system injury, including for mild damage
associated with surgically-induced circulation arrest.

J Thorac Cardiovasc Surg. 2008 May;135(5):1110-9, 1119.e1-10.

Myocardial injury in coronary artery bypass grafting: on-pump versus off-pump
comparison by measuring high-sensitivity C-reactive protein, cardiac troponin I, 
heart-type fatty acid-binding protein, creatine kinase-MB, and myoglobin release.

Chowdhury UK, Malik V, Yadav R, Seth S, Ramakrishnan L, Kalaivani M, Reddy SM,
Subramaniam GK, Govindappa R, Kakani M.

Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical
Sciences, New Delhi, India. ujjwalchow@rediffmail.com

OBJECTIVES: We sought to investigate the release pattern of different cardiac
biomarkers (high-sensitivity C-reactive protein, cardiac troponin I, heart-type
fatty acid-binding protein, creatine kinase-MB, and myoglobin) and to establish
the diagnostic discrimination limits of each marker protein to evaluate
perioperative myocardial injury in patients undergoing coronary artery bypass
grafting with or without cardiopulmonary bypass. METHODS: Fifty patients were
randomly assigned to on-pump or off-pump coronary artery bypass grafting. All
cardiac biomarkers were measured in serial venous blood samples drawn before
heparinization in both groups and after aortic unclamping at 1, 2, 4, 8, 24, 48, 
and 72 hours in the on-pump group. In the off-pump group samples were taken after
the last distal anastomosis and at same time intervals as in the on-pump group.
RESULTS: The total amount of heart-type fatty acid-binding protein, cardiac
troponin I, and high-sensitivity C-reactive protein released was significantly
higher in the on-pump group than in the off-pump group. Receiver operating
characteristic curve analysis of cardiac biomarkers indicated cardiac troponin I 
and heart-type fatty acid-binding protein as the superior diagnostic
discriminators of myocardial injury, with an optimal cutoff value of greater than
0.92 ng/mL (area under the curve, 0.95 [95% CI, 0.88-1.00]; sensitivity, 92%;
specificity, 92%; likelihood ratio [+], 11.50) and greater than 6.8 ng/mL (area
under the curve, 0.94 [95% CI, 0.88-1.00]; sensitivity, 88%; specificity, 88%;
likelihood ratio [+], 7.33), respectively. Logistic regression analysis revealed 
that patients with increased cardiac troponin I levels of greater than 0.92 ng/mL
and heart-type fatty acid-binding protein levels of greater than 6.8 ng/mL were
at 132.25 (95% confidence interval, 17.14-1020.49) times and 53.77 (95%
confidence interval, 9.76-296.12) times higher risk of myocardial injury after
on-pump coronary artery bypass grafting. CONCLUSIONS: Off-pump coronary artery
bypass grafting provides better myocardial protection than on-pump coronary
artery bypass grafting. Cardiac troponin I and heart-type fatty acid-binding
protein, but not high-sensitivity C-reactive protein, served as superior
diagnostic discriminators of perioperative myocardial damage after on-pump
coronary artery bypass grafting.

Cytokine. 2008 Jun;42(3):317-24. Epub 2008 Apr 15.

Risk stratification in neonates and infants submitted to cardiac surgery with
cardiopulmonary bypass: A multimarker approach combining inflammatory mediators, 
N-terminal pro-B-type natriuretic peptide and troponin I.

Carmona F, Manso PH, Vicente WV, Castro M, Carlotti AP.

Division of Pediatric Critical Care Medicine, Department of Pediatrics, Hospital 
das Clinicas, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo,
Avenida dos Bandeirantes, 3900, Campus Universitario, Ribeirao Preto, SP, CEP
14049-900, Brazil.

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery 
with cardiopulmonary bypass (CPB) in neonates and infants, and its early
recognition remains a challenging task. We aimed to test whether a multimarker
approach combining inflammatory and cardiac markers provides complementary
information for prediction of LCOS and death in children submitted to cardiac
surgery with CPB. Forty-six children younger than 18 months with congenital heart
defects were prospectively enrolled. No intervention was made. Blood samples were
collected pre-operatively, during CPB and post-operatively (PO) for measurement
of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, cardiac
troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP).
Clinical data and outcome variables were recorded. Logistic regression was used
to identify predictors of LCOS and death. Multivariate logistic regression
identified pre-operative NT-proBNP and IL-8 4h PO as independent predictors of
LCOS, while cTnI 4h PO and CPB length were independent predictors of death. The
use of inflammatory and cardiac markers in combination improved sensitivity,
negative predictive value and accuracy of the models. In conclusion, the combined
assessment of inflammatory and cardiac biochemical markers can be useful for
identifying young children at increased risk for LCOS and death after heart
surgery with CPB.