Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation.

Introduction: Primary mitral valve regurgitation (MR) results from degeneration of mitral valve apparatus. Mechanisms leading to incomplete postoperative left ventricular (LV) reverse remodeling (Rev-Rem) despite timely and successful surgical mitral valve repair (MVR) remain unknown. Plasma exosomes (pEXOs) are smallest nanovesicles exerting early postoperative cardioprotection. We hypothesized that late plasma exosomal microRNAs (miRs) contribute to Rev-Rem during the late postoperative period. Methods: Primary MR patients (n = 19; age, 45-71 years) underwent cardiac magnetic resonance imaging and blood sampling before (T0) and 6 months after (T1) MVR. The postoperative LV Rev-Rem was assessed in terms of a decrease in LV end-diastolic volume and patients were stratified into high (HiR-REM) and low (LoR-REM) LV Rev-Rem subgroups. Isolated pEXOs were quantified by nanoparticle tracking analysis. Exosomal microRNA (miR)-1, -21-5p, -133a, and -208a levels were measured by RT-qPCR. Anti-hypertrophic effects of pEXOs were tested in HL-1 cardiomyocytes cultured with angiotensin II (AngII, 1 µM for 48 h). Results: Surgery zeroed out volume regurgitation in all patients. Although preoperative pEXOs were similar in both groups, pEXO levels increased after MVR in HiR-REM patients (+0.75-fold, p = 0.016), who showed lower cardiac mass index (-11%, p = 0.032). Postoperative exosomal miR-21-5p values of HiR-REM patients were higher than other groups (p < 0.05). In vitro, T1-pEXOs isolated from LoR-REM patients boosted the AngII-induced cardiomyocyte hypertrophy, but not postoperative exosomes of HiR-REM. This adaptive effect was counteracted by miR-21-5p inhibition. Summary/Conclusion: High levels of miR-21-5p-enriched pEXOs during the late postoperative period depict higher LV Rev-Rem after MVR. miR-21-5p-enriched pEXOs may be helpful to predict and to treat incomplete LV Rev-Rem after successful early surgical MVR.

Big gamma-glutamyltransferase is associated with epicardial fat volume and cardiovascular outcome in the general population.

AIMS: Gamma-glutamyltransferase (GGT) has been recognized as a cardiovascular risk factor, and its highest molecular weight fraction [big GGT (b-GGT)] is found in vulnerable atherosclerotic plaques. We explored the relationship between b-GGT, computed tomography findings, and long-term outcomes in the general population. METHODS AND RESULTS: Between May 2010 and October 2011, subjects aged 45-75 years living in a Tuscan city and without known cardiac disease were screened. The primary endpoint was a composite of cardiovascular death or acute coronary syndrome requiring urgent coronary revascularization. Gamma-glutamyltransferase fractions were available in 898 subjects [median age 65 years (25th-75th percentile 55-70), 46% men]. Median plasma GGT was 20 IU (15-29), and b-GGT was 2.28 (1.28-4.17). Coronary artery calcium (CAC) score values were 0 (0-60), and the volume of pro-atherogenic epicardial fat was 155 mL (114-204). In a model including age, sex, low-density lipoprotein (LDL) cholesterol, current or previous smoking status, hypertension, diabetes, obesity, b-GGT independently predicted epicardial fat volume (EFV) (r = 0.162, P < 0.001), but not CAC (P = 0.198). Over a 10.3-year follow-up (9.6-10.8), 27 subjects (3%) experienced the primary endpoint. We evaluated couples of variables including b-GGT and a cardiovascular risk factor, CAC or EFV. Big GGT yielded independent prognostic significance from age, LDL cholesterol, current or previous smoking status, hypertension, diabetes, obesity, but not CAC or EFV. Conversely, GGT predicted the primary endpoint even independently from CAC and EFV. CONCLUSION: Big GGT seemed at least as predictive as the commonly available GGT assay; therefore, the need for b-GGT rather than GGT measurement should be carefully examined.

Plasma exosomes characterization reveals a perioperative protein signature in older patients undergoing different types of on-pump cardiac surgery.

Although exosomes are extracellular nanovesicles mainly involved in cardioprotection, it is not known whether plasma exosomes of older patients undergoing different types of on-pump cardiac surgery protect cardiomyocytes from apoptosis. Since different exosomal proteins confer pro-survival effects, we have analyzed the protein cargo of exosomes circulating early after aortic unclamping. Plasma exosomes and serum cardiac troponin I levels were measured in older cardiac surgery patients (NYHA II-III) who underwent first-time on-pump coronary artery bypass graft (CABG; n = 15) or minimally invasive heart valve surgery (mitral valve repair, n = 15; aortic valve replacement, n = 15) at induction of anesthesia (T0, baseline), 3 h (T1) and 72 h (T2) after aortic unclamping. Anti-apoptotic role of exosomes was assessed in HL-1 cardiomyocytes exposed to hypoxia/re-oxygenation (H/R) by TUNEL assay. Protein exosomal cargo was characterized by mass spectrometry approach. Exosome levels increased at T1 (P < 0.01) in accord with troponin values in all groups. In CABG group, plasma exosomes further increased at T2 (P < 0.01) whereas troponin levels decreased. In vitro, all T1-exosomes prevented H/R-induced apoptosis. A total of 340 exosomal proteins were identified in all groups, yet 10% of those proteins were unique for each surgery type. In particular, 22 and 12 pro-survival proteins were detected in T1-exosomes of heart valve surgery and CABG patients, respectively. Our results suggest that endogenous intraoperative cardioprotection in older cardiac surgery patients is early mediated by distinct exosomal proteins regardless of surgery type.

Differential modulatory effects of Propofol and Sevoflurane anesthesia on blood monocyte HLA-DR and CD163 expression during and after cardiac surgery with cardiopulmonary bypass: a preliminary randomized flow cytometry study.

INTRODUCTION: The increase of the anti-inflammatory CD163highHLA-DRlow blood monocyte subset is one of the mechanisms dampening inflammation during cardiac surgery with cardiopulmonary bypass. We evaluated the effect of two different anesthetic protocols, intravenous Propofol infusion or Sevoflurane-gas administration, on the perioperative frequency of this subset. METHODS: Blood from patients (Propofol = 11, Sevoflurane = 13) undergoing minimally invasive mitral valve surgery was drawn preoperatively (T1), before declamping (T2), at 6 (T3), 24 (T4), 48 (T5), and 72 hours (T6) after declamping. C-reactive protein, haptoglobin, and lactate dehydrogenase were measured. A hemolytic index, as C-reactive protein/haptoglobin ratio, was introduced. Monocyte expression of HLA-DR, CD163, and the CD163highHLA-DRlow subset fraction was quantified by flow cytometry. Baseline-referred variations of plasmatic and cellular data at T2 were normalized for clamping times. Subsequent time-point variations were normalized for the final cardiopulmonary bypass times. RESULTS: Variations of hemolytic index and lactate dehydrogenase were higher with Propofol at T3 (p = 0.004 and p = 0.02, respectively) when compared with Sevoflurane. At T2, the down-modulation of CD163 was higher with Propofol (p = 0.005). Starting from T3, the up-regulatory trend of CD163 was basically higher with Propofol, although not significantly. Propofol induced higher increments of HLA-DR low fractions, at T2 (p = 0.04) and, to a lesser extent, at T4 (p = 0.06). Starting from T3, the CD163highHLA-DRlow subset variations were higher with Propofol, especially at T4 and T6. CONCLUSION: Propofol seems to induce a higher postoperative fraction of the CD163highHLA-DRlow monocyte subset. This could represent either a compensatory mechanism dampening the higher inflammatory condition observed with Propofol at T2 or a consequence of a higher postoperative Propofol-induced hemolysis.

Emerging Biomarkers of Oxidative Stress in Acute and Stable Coronary Artery Disease: Levels and Determinants.

BACKGROUND: Oxidative stress is crucial in the pathogenesis of atherosclerosis and acute myocardial infarction (AMI). Under the generic terms "oxidative stress" (OS), many biomarkers belonging to different pathways have been proposed. AIM: To compare the levels of recently proposed OS-related parameters in acute coronary syndromes (ACS) and stable coronary artery disease (CAD), to evaluate their effectiveness as additive risk or illness indicators of stable and acute ischemic events, and their response over time during the course of AMI. METHODS: 76 ACS, 77 CAD patients, and 63 controls were enrolled in the study. Different OS-related biomarkers, including reactive oxygen metabolites (ROM), the total antioxidant capacity (OXY), nitrite/nitrate (final nitric oxide products, NOx), and Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), were evaluated. Moreover, time response during AMI course (admission, and 6, 12, 18, 24, 36, and 48 hours after, T0-T6, respectively) and correlation with traditional cardiovascular (CV) risk factors (age, gender, hypertension, diabetes mellitus, dyslipidemia, smoking habit) were also assessed. RESULTS: Over time, ROM progressively increased while OXY and NOx decreased. Kinetics of LOX-1 during AMI shows that this biomarker boosts early during the acute event (T1 and T2) and then progressively decreases, being significantly lower from T0 to T6. Different OS-related biomarkers were differentially associated with CV risk factors and CAD or ACS presence. CONCLUSION: Differences in OS-related biomarkers (between groups, according to the response over time during AMI, and to the presence of CV risk factors) confirmed OS involvement in the transition from healthy status to stable CAD and ACS, although evidencing the heterogeneous nature of redox processes. In future, a multi-marker panel including different biomarkers and pathways of oxidative stress could be evaluated as an additive tool to be used in the CV prevention, diagnosis, patient stratification, and treatment.

Effect of iodinated contrast medium on thyroid function: a study in children undergoing cardiac computed tomography.

BACKGROUND: Few studies, and with conflicting results, have evaluated the potential effects of iodinated contrast media on children's thyroid function. OBJECTIVE: To investigate the effects of iodinated contrast medium on thyroid function in neonates, infants and young children with congenital heart disease undergoing cardiac computed tomography (CT). MATERIALS AND METHODS: We retrospectively evaluated 10 neonates (group 1) and 23 infants and young children (group 2) without thyroid or renal disease for serum levels of thyroid-stimulating hormone, free triiodothyronine and free thyroxine before contrast-enhanced cardiac CT, 48 h after CT and at discharge from the hospital. Cardiac CT was performed with intravenous administration of 1.14±0.17 mL/kg of body weight of iopromide (containing 370 mg of iodine/mL). RESULTS: Group 1 had a reduction of thyroid-stimulating hormone from baseline to 48 h post injection (P=0.002). Group 2 had a reduction of thyroid-stimulating hormone median levels from baseline to 48 h post injection and an increase from 48 h to discharge (P=0.0005 and P=0.0001, respectively). CONCLUSION: Intravenous iodinated contrast medium in children with congenital heart disease caused transient thyroid-stimulating hormone decrease 48 h after CT, with thyroid-stimulating hormone returning to normal range at discharge.

Diagnostic accuracy and prognostic valued of plasmatic Cystatin-C in children undergoing pediatric cardiac surgery.

BACKGROUND: Diagnosis and treatment of acute kidney injury (AKI) is often delayed in children after cardiac surgery due to the lack of an early biomarker of renal damage. Our aim was to evaluate the diagnostic accuracy of plasma cystatin-C as an early biomarker of AKI and its prognostic value in pediatric cardiac surgery. METHODS: Cystatin-C and creatinine were measured pre-operatively and at 2-6-12h post-surgery. The primary outcome was: AKI (defined as an increase of ≥1.5 of plasma creatinine from baseline) and a composite marker, including major complications and/or extubation time>15days. Risk was evaluated using Cox proportional hazards regression analysis, considering some continuous predictors in the basal model (i.e., age, body surface area and Aristotle-score) to which cystatin-C peak values were added. Discrimination, calibration, and reclassification tests were also performed. RESULTS: 248 children (140 males) undergoing cardiac surgery (median age 6.5months; IQR: 1.7-40.1months; range 0-17years) have been enrolled. Post operatory Cystatin-C values were found to be an early diagnostic marker of AKI showing the best area under the ROC curve value (AUC) at 12h (0.746, CI 95% 0.674-0.818). In the multivariable analyses, peak cystatin-C values showed a significant hazard ratio (HR=2.665, CI 95% 1.750-4.059, p<0.001). Finally, post operatory cystatin-C at 12h significantly improved the AUC (p=0.017) compared to basal model, resulting a net gain in reclassification proportion (NRI=0.417, p<0.001). CONCLUSIONS: Our data show that cystatin-C should be considered an early biomarker of AKI, improving the risk prediction for complicated outcome in pediatric cardiac surgery.

Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors.

BACKGROUND: The routine use of brain natriuretic peptide (BNP) in pediatric cardiac surgery remains controversial. Our aim was to test whether BNP adds information to predict risk in pediatric cardiac surgery. METHODS: In all, 587 children undergoing cardiac surgery (median age 6.3 months; 1.2-35.9 months) were prospectively enrolled at a single institution. BNP was measured pre-operatively, on every post-operative day in the intensive care unit, and before discharge. The primary outcome was major complications and length ventilator stay >15 days. A first risk prediction model was fitted using Cox proportional hazards model with age, body surface area and Aristotle score as continuous predictors. A second model was built adding cardiopulmonary bypass time and arterial lactate at the end of operation to the first model. Then, peak post-operative log-BNP was added to both models. Analysis to test discrimination, calibration, and reclassification were performed. RESULTS: BNP increased after surgery (p<0.001), peaking at a mean of 63.7 h (median 36 h, interquartile range 12-84 h) post-operatively and decreased thereafter. The hazard ratios (HR) for peak-BNP were highly significant (first model HR=1.40, p=0.006, second model HR=1.44, p=0.008), and the log-likelihood improved with the addition of BNP at 12 h (p=0.006; p=0.009). The adjunction of peak-BNP significantly improved the area under the ROC curve (first model p<0.001; second model p<0.001). The adjunction of peak-BNP also resulted in a net gain in reclassification proportion (first model NRI=0.089, p<0.001; second model NRI=0.139, p=0.003). CONCLUSIONS: Our data indicates that BNP may improve the risk prediction in pediatric cardiac surgery, supporting its routine use in this setting.

The low triiodothyronine syndrome: a strong predictor of low cardiac output and death in patients undergoing coronary artery bypass grafting.

BACKGROUND: There is strong clinical and experimental evidence that altered thyroid homeostasis negatively affects survival in cardiac patients, but a negative effect of the low triiodothyronine (T3) syndrome on the outcome of coronary artery bypass grafting (CABG) has not been demonstrated. This study was designed to evaluate the prognostic significance of low T3 syndrome in patients undergoing CABG. METHODS: The thyroid profile was evaluated at hospital admission in 806 consecutive CABG patients. Known thyroid disease, severe systemic illness, and use of drugs interfering with thyroid metabolism were considered exclusion criteria. The effect of the baseline free T3 (fT3) concentration and of preoperative low T3 syndrome (fT3 <2.23 pmol/L) on the risk of low cardiac output (CO) and death was analyzed in a logistic regression model. RESULTS: There were 19 (2.3%) deaths, and 64 (7.8%) patients experienced major complications. After univariate analysis, fT3, low T3, New York Heart Association class greater than II, low left ventricular ejection fraction (LVEF), and emergency were associated with low CO and hospital death. History of atrial fibrillation, cardiopulmonary bypass time, and peripheral vascular disease were associated only with low CO. At multivariate analysis, only fT3, low T3, emergency, and LVEF were associated with low CO, and fT3 (odds ratio, 0.172, 95% confidence interval, 0.078 to 0.379; p < 0.0001) and LVEF (odds ratio, 0.934, 95% confidence interval, 0.894 to 0.987; p = 0.03) were the only independent predictors of death. CONCLUSIONS: Our study demonstrates that low T3 is a strong predictor of death and low CO in CABG patients. For this reason, the thyroid profile should be evaluated before CABG, and patients with low T3 should be considered at higher risk and treated accordingly.

Response of cardiac endocrine function to surgery stress is age dependent in neonates and children with congenital heart defects: consequences in diagnostic and prognostic accuracy of brain natriuretic peptide measurement.

OBJECTIVE: The aim of this study was to evaluate the diagnostic and prognostic accuracy of brain natriuretic peptide assay in neonates and children undergoing surgery for congenital heart disease. DESIGN: Prospective, observational study. SETTING: Single center. PATIENTS: We enrolled 336 consecutive children (median age, 6 mo [range, 0-37 mo]) undergoing cardiac surgery (87 neonates; age, 7 d [5-12]; median, 25th-75th percentile; 24 infants and children; age, 11 mo [4-60]) and 436 healthy controls. INTERVENTIONS: Brain natriuretic peptide was measured preoperatively, on every postoperative day in the ICU, and at discharge. Intubation time was the primary outcome. MEASUREMENTS AND MAIN RESULTS: Preoperative brain natriuretic peptide values in patients with congenital heart disease were higher than those in controls (p < 0.01). Brain natriuretic peptide had a good diagnostic accuracy in discriminating between patients with congenital heart disease and healthy controls with an area under the curve = 0.918 for neonates and area under the curve = 0.894 for older children. The best cutoff values, calculated by receiver operating characteristic analysis, were different for the two age subgroups with cutoff values of 363.5 ng/L for neonates and 23.5 ng/L for older children. At 24 hours after surgery, although brain natriuretic peptide decreased in neonates (baseline 2723 vs 1290 ng/L, p < 0.001), it increased in children (60 vs 365 ng/L at 24 hours, p < 0.001). Multivariable analysis identified the preoperative level of brain natriuretic peptide in infant/children and the difference in brain natriuretic peptide value (baseline 24 hours) in neonates, as independent predictors of intubation time. Furthermore, body surface area, Aristotle score, and cardiopulmonary bypass time had an independent significant effect on the endpoint in either group. CONCLUSIONS: Baseline cardiac endocrine function and its response to surgical stress are dependent on age in neonates and children, undergoing cardiac surgery for congenital heart disease. Brain natriuretic peptide shows a good diagnostic and prognostic accuracy in this setting, with different features in either neonates or infants/children subsets.

Reference values for urinary neutrophil gelatinase-associated lipocalin (NGAL) in pediatric age measured with a fully automated chemiluminescent platform.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has been suggested as the most promising biomarker of acute kidney injury. However, there are no reliable data on analytical sensitivity and reference limits of urinary NGAL (uNGAL) assay in pediatric age. The aim of the present study is to evaluate the analytical sensitivity and the reference range of uNGAL measured in urine specimens of pediatric age with the fully automated platform ARCHITECT i1000. METHODS: A total of 333 urine samples were collected from 25 healthy newborns (16 males and 9 females; age 1-4 days) and 308 children (150 males and 147 females; mean age 80.7 months, range 0.63-248 months) and assayed for uNGAL by two different Italian centers (Department of Laboratory Medicine of the Fondazione Toscana G. Monasterio of Pisa and Massa and the Clinical Pathology Laboratory Unit of Istituto Giannina Gaslini of Genova). RESULTS: The calculated limits of blank (LOB) and detection (LOD) values were 0.5 ng/mL and 0.95 ng/mL, respectively. The distribution of uNGAL values approximated a log-normal distribution (median 5.2 ng/mL, interquartile range 2.5-12.8 ng/mL, 99th percentile 117.6 ng/mL). uNGAL values of the 25 neonates were significantly higher than those of 308 children (neonates: mean 44.2 ng/mL, median 30.3 ng/mL, range 5.2-137.4 ng/mL; children: mean 10.2 ng/mL, median 4.6 ng/mL, range 0.2-146.7 ng/mL; p<0.0001). CONCLUSIONS: uNGAL assay shows a good analytical sensitivity and imprecision, which allows the measurement of uNGAL values around the cut-off value (i.e., 117.6 ng/mL) with an imprecision <5 CV%. The distribution of uNGAL values in pediatric age approximates a log-normal distribution, with values which are higher in neonates compared to children.

Thyroid and brain natriuretic Peptide response in children undergoing cardiac surgery for congenital heart disease- age-related variations and prognostic value.

BACKGROUND: Interest in hormonal response after pediatric cardiac surgery is growing, but many aspects remain unclear. The aim of this study was to test age-related variations and prognostic values of thyroid hormones, and brain natriuretic peptide (BNP) levels before and after surgery. METHODS AND RESULTS: A total of 162 children undergoing cardiac surgery were divided into 3 age groups (group 1, n=57 neonates; group 2, n=58 infants; group 3, n=47 toddlers). Free thyroid hormones (fT3 and fT4), thyrotropin (thyroid-stimulating hormone [TSH]) and BNP were measured preoperatively, daily postoperatively in the intensive care unit and after 15 days. The primary outcome was time to extubation (TTE; variable used as time to event by survival analysis). The hormonal response differed among age groups. In older children the TSH nadir occurred at 6-12h after surgery (0.42 mIU/L, P<0.001), with a progressive recovery thereafter, while in neonates the TSH nadir occurred later, at 36-60 h (0.14 mIU/L, P<0.001), followed by a much slower recovery. In neonates, BNP also dropped after surgery (from 2,899 to 824.0 ng/L, P<0.001) while increased in older children (from 71.00 to 527.00 ng/L, P<0.001). On multivariate analysis independent predictors of TTE were fT3 nadir in all age groups, together with TSH nadir and Aristotle score in neonates, and body surface area and BNP peak in older children. CONCLUSIONS: BNP and thyroid response after pediatric cardiac surgery differs widely according to age. Beside Aristotle score, combined measurement of fT3 and TSH are the strongest predictors of TTE, especially in neonates.

The combined use of neutrophil gelatinase-associated lipocalin and brain natriuretic peptide improves risk stratification in pediatric cardiac surgery.

BACKGROUND: The aim of this study is to test the hypothesis whether the combined use of a cardio-specific biomarker, the brain natriuretic peptide (BNP) and a marker of early renal damage, the assay of urinary neutrophil gelatinase-associated lipocalin (uNGAL), may improve risk stratification in pediatric cardiac surgery. METHODS: We prospectively enrolled 135 children [median age 7 (interquartile range 1-49) months] undergoing to cardiac surgery for congenital heart disease. All biomarkers were evaluated pre- and post-operatively at different times after cardiopulmonary-bypass (CPB): uNGAL at 2, 6 and 12 h; BNP at 12 and 36 h; serum creatinine at 2, 6, 12, and 36 h. Primary endpoints were development of acute kidney injury (AKI) (defined as 1.5 serum creatinine increase) and intubation time. RESULTS: AKI occurred in 39% of patients (65% neonates and 32% older children, p=0.004). The peak of uNGAL values occurred more frequently at 2 h. uNGAL values at 2 h [median 28.2 (interquartile range 7.0-124.6) ng/L] had a good diagnostic accuracy for early diagnosis of AKI with an AUC (area under the curve) ROC (receiver operating characteristic) curve of 0.85 (SE 0.034). Using multivariable logistic regression analysis, development of AKI was significantly associated with uNGAL values at 2 h after CPB [OR=1.88 (1.30-2.72, p=0.001)], together with the CPB time and Aristotle score, as an index of complexity of the surgical procedure, while pre-operative BNP values were not. Furthermore, uNGAL and pre-operative BNP values (together with Aristotle score) were significantly associated with adverse outcome (longer intubation time and mortality). CONCLUSIONS: Pre-operative BNP and uNGAL values after surgery (together with the Aristotle score) were independently associated with a more severe course and worse outcome in children undergoing cardiac surgery for congenital heart disease.

Adiponectin plasma levels decrease after surgery in pediatric patients with congenital heart disease.

OBJECTIVE: Adiponectin is a protein secreted by adipose tissue and involved in inflammatory process as well as in metabolic regulation. The aim of this study was to examine the response of plasma adiponectin to cardiac surgery in children with congenital defects to determine whether its measurement is associated to the response to injury. DESIGN AND METHODS: Twenty-five pediatric patients undergoing heart surgery for correction of congenital defects were studied. Adiponectin plasma levels, obtained pre- and three times postoperatively, were determined by dedicated ELISA. Brain natriuretic peptide (BNP) plasma levels were also determined. RESULTS: Adiponectin levels are highest in the first month of life (p=0.004 newborns vs. children) with a progressive fall in the next few years. After surgery, adiponectin increased slowly over a 1-month period, following an initial decrease in the first 3 days. CONCLUSIONS: Adiponectin could be involved in the acute response to injury although further investigation into the relationship between adiponectin, glucose regulation and inflammatory process is necessary to examine the issue of the adiponectin decrease after surgery from a more integrated prospective.

Diagnostic accuracy and clinical relevance of brain natriuretic peptide assay in pediatric patients with congenital heart diseases.

BACKGROUND: The clinical usefulness of B-type natriuretic peptide (BNP) assay in congenital heart diseases is still controversial. We evaluated the diagnostic accuracy and clinical relevance of this assay in different cardiovascular hemodynamic conditions in pediatric patients with congenital heart diseases. MATERIALS AND METHODS: BNP was measured in 173 healthy individuals and in 382 pediatric patients with congenital heart diseases. We identified five subgroups of hemodynamic conditions: left ventricular volume overload, right ventricular volume overload, left ventricular pressure overload, right ventricular pressure overload, and biventricular volume overload. RESULTS: BNP was higher (P<0.0001) in patients (median 49.0 ng/l, range 0.45-14363 ng/l) than in the reference population (median 6.1 ng/l, range 1.0-29.7 ng/l). BNP assay showed a good diagnostic accuracy in discriminating between healthy individuals and patients (area under the receiver operating characteristic curve 0.95, SE 0.009). Lower BNP values were found in right ventricular pressure overload than in left ventricular pressure overload, left ventricular volume overload, or biventricular volume overload. In the left ventricular volume overload subgroup, BNP significantly correlated with peak systolic gradients (rho=0.622, P<0.001) and left ventricular dilatation (rho=0.35, P=0.03). In the right ventricular volume overload subgroup, BNP correlated with right ventricular pressure (rho=0.622, P<0.001) and right ventricular dilatation (rho=0.377, P=0.0077). Moreover, in cyanotic defects, BNP showed a significant correlation with O2 saturation (rho=0.204 P=0.0128). CONCLUSION: BNP assay showed a good diagnostic accuracy in discriminating between healthy individuals and patients. Congenital heart disease with left ventricular pressure overload and biventricular volume overload has higher BNP values than that with right ventricular pressure overload.

Heat shock protein 70-1 gene expression in pediatric heart surgery using blood cardioplegia.

BACKGROUND: In response to many stress stimuli, cardiomyocytes produce a common set of heat shock proteins (HSP). Up-regulation of HSP70-1 (the inducible isoform) is known to reduce the risk of myocardial cell damage during open-heart surgery and seems to be protective against ischemia. We assessed hsp70-1 gene expression during blood cardioplegic arrest in children undergoing surgical correction of congenital heart defects. METHODS: In tissue samples taken from the right atrium of 59 pediatric patients, we examined hsp70-1 gene expression using a real-time quantitative reverse transcription PCR, with 18S rRNA as internal standard. RESULTS: On average, hsp70-1 gene expression was higher than the baseline level by a factor of 1.44+/- 0.17 (mean+/-SEM). A significant relationship between hsp70-1 mRNA levels and aortic cross-clamp time was observed (R(2)=0.069, p=0.044). Conversely, no significant correlation was observed between hsp70-1 mRNA levels and temperature. CONCLUSIONS: These data suggest that blood cardioplegia can induce an increment in the expression of hsp70-1, confirming its protective role in ischemia/reperfusion injury.

The double balloon cannula: a means to prevent backward flow of retrograde cardioplegia to the right atrium.

Retrograde cardioplegia (RC) delivery may result in suboptimal myocardial protection, due to leakage of cardioplegia to the right atrium. This study was undertaken to assess the efficacy of a double balloon cannula (DBC) occluding the coronary sinus ostium during RC. Fifteen patients were randomly assigned to receive RC via a conventional cannula or via the DBC. Cardioplegia was started at 200 ml/min, and the flow rate (Q) was adjusted to obtain a perfusion pressure (P) of 25-40 mmHg. Blood samples were collected at 13 different time points. The CPK-MB and TnI levels were measured on each sample. The use of the DBC was associated with increased P (P=0.03) at a lower Q (P=0.02). The CK-MB levels were significantly increased in both groups (P<0.0001). However, the use of the DBC was associated with lower levels of CK-MB (P=0.002). A similar trend was observed for the TnI levels (peak 5.1+/-1.8 ng/ml vs. 8.7+/-5 ng/ml, P=0.11). Occlusion of the coronary sinus ostium improved the hemodynamic efficiency of the RC, and this resulted in reduced perioperative ischemic myocardial damage.

The non-thyroidal illness syndrome after coronary artery bypass grafting: a 6-month follow-up study.

The non-thyroidal illness syndrome (NTIS) is considered a transient and completely reversible phenomenon, but it has been shown that it may last for several days postoperatively after coronary artery bypass grafting (CABG) surgery. This study was undertaken to assess thyroid function 6 months after uncomplicated CABG. The thyroid profile was evaluated in 40 consecutive patients undergoing CABG preoperatively, at 0, 12, 48, and 120 h postoperatively, and at 6-month follow-up. Triiodothyronine (T3), free T3 (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were assayed using a microparticle enzyme immunoassay. T4 and total serum thyroid hormone-binding capacity (T-uptake) were measured on the same samples using a fluorescence polarization immunoassay. Patients with severe systemic illness and patients treated with amiodarone were excluded. All patients were euthyroid at admission. Mean age was 67.4+/-9.0 years. There were 31 (77.5%) men. Typical NTIS was observed in all patients, and the FT3 concentration was still reduced by postoperative day 5 (p<0.0001). At 6-month follow-up, all patients were free from cardiac symptoms, and no new cardiac events were recorded. The thyroid profile was normal in 35 patients (87.5%). One patient (4.5%) had developed overt hypothyroidism. Two patients had isolated low T3 and FT3 levels with normal TSH. Two patients had moderately increased FT3 levels with suppressed TSH. In most uncomplicated patients, thyroid function returns to normal 6 months after CABG. However, we observed significant alterations of the thyroid profile in 5 out of 40 patients. Further studies are needed to define the long-term consequences of postoperative NTIS.