[Low cardiac output syndrome score to evaluate postoperative cardiac surgery patients in a pediatric intensive care unit]. / Çocuk yogun bakim ünitesinde kardiyak cerrahi sonrasi hastalarin degerlendirilmesinde kullanilan düsük kardiyak debi sendromu skorlamasi.

OBJECTIVE: There is no clear consensus regarding the definition of low cardiac output syndrome (LCOS) or the follow-up of this patient group. Given this lack of a clinical definition, the aim of this study was to use a LCOS score (LCOSs) similar to the low cardiac output score previously presented in the literature and evaluate the relationship between a high LCOSs and poor clinical outcome. METHODS: A total of 54 patients were prospectively evaluated after cardiac surgery. The LCOSs was used to evaluate the deve-lopment of low cardiac output. Each parameter was scored as 1 point. The score was calculated every hour for 24 hours postoperatively and the highest score was recorded as the peak score (pLOCSs). The LOCSs at the time of admission to the pediatric intensive care unit, at the 4th, 8th, and 16th hour were recorded and a cumulative score (cLOCSs) score was calculated. RESULTS: The mean age of the patients was 49.40±53.15 months and 24.07% had LOCS. In the group with LCOS, the cLOCSs, vasoactive-inotropic score (VIS), lactate mean, aortic clamp time, and the total cardiopulmonary bypass time were significantly higher. In this study, a significant and positive correlation was found between the cLOCSs and pLOCSs and the length of hospital stay, length of stay in the pediatric intensive care unit, VIS, lactate mean, and aortic clamp duration. CONCLUSION: The objective of this study was to draw attention to the potential use of a common language in the care of critical pediatric patients undergoing cardiac surgery with a previously defined scoring method that includes parameters indicating poor perfusion in the patient.

A sex-balanced rodent model for evaluating phosphine inhalation toxicity.

Exposure to phosphine (PH3 ), a common grain fumigant, is characterized by diverse nonspecific symptoms and a high mortality rate. Although PH3 poisoning is thought to target oxidative respiration, the exact mechanism of action remains largely unknown, resulting in limited treatment options. In our study, the effects of PH3 on female rats were assessed to elucidate potential sex-specific differences and obtain a more comprehensive understanding of PH3 toxicity. Lethality, physiology, and behavior were evaluated in female rats exposed to gaseous PH3 (13,200-26,400 ppm × min), and results were compared with corresponding findings in male rats. Median lethal concentration-time (LCt50 ) and time of death (tTOD ) did not differ significantly between the sexes. Cardiopulmonary changes induced by PH3 were also of comparable magnitude, although temporally, respiratory responses occurred earlier and cardiovascular variations manifested later in female rats. Behavioral observations corroborated physiological findings and indicated a response to hypoxic conditions and low cardiac output. Together, these results provided insights on the toxic mechanisms of PH3 , in particular, its potential interference with oxygen transport and circulation.

Developmental Pharmacokinetics and Age-Appropriate Dosing Design of Milrinone in Neonates and Infants with Acute Kidney Injury Following Cardiac Surgery.

BACKGROUND AND OBJECTIVE: Milrinone is used for the prevention of low cardiac output syndrome in pediatric patients after cardiac surgery. Milrinone is mainly eliminated by the kidneys; however, there is limited information on milrinone pharmacokinetics in infants who have acute kidney injury (AKI). The aim of this study was to develop a milrinone population pharmacokinetic model in neonates and infants with or without AKI. The developed milrinone pharmacokinetic model was utilized for a Monte Carlo simulation analysis to identify age-appropriate dosing regimens in neonates and infants. METHODS: Population pharmacokinetic analysis was performed with a total of 1088 serum milrinone concentrations obtained from 92 infants as part of a prospective clinical study in neonates and infants following cardiac surgery (ClinicalTrials.gov identifier NCT01966237). AKI stages were determined based on the Kidney Injury Improving Global Outcomes (KDIGO) Clinical Practice Guideline within the first three postoperative days. RESULTS: A two-compartment model was found to adequately describe the pharmacokinetic data. Allometrically scaled body weight, AKI stages, and maturation function were identified as significant predictors of milrinone clearance. The proposed dosing regimens for milrinone continuous infusions were determined based on a target concentration attainment of simulated steady-state concentration and covered three age groups across 0-12 months of age for each AKI stage. CONCLUSION: This study provides a milrinone population pharmacokinetic model in neonates and infants and captures the developmental changes in clearance. Age-appropriate dosing regimens were determined based on the simulation analysis with the developed pharmacokinetic model. The findings will facilitate model-informed precision dosing of milrinone in infants with or without AKI.

Evaluation of the vasoactive-inotropic score, mid-regional pro-adrenomedullin and cardiac troponin I as predictors of low cardiac output syndrome in children after congenital heart disease surgery.

OBJECTIVE: To determine the predictive value of the inotropic score (IS) and vasoactive-inotropic score (VIS) in low cardiac output syndrome (LCOS) in children after congenital heart disease surgery involving cardiopulmonary bypass (CPB), and to establish whether mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I), associated to the IS and VIS scores, increases the predictive capacity in LCOS. DESIGN: A prospective observational study was carried out. SETTING: A Paediatric Intensive Care Unit. PATIENTS: A total of 117children with congenital heart disease underwent CPB. Patients were divided into two groups: LCOS and non-LCOS. INTERVENTIONS: The clinical and analytical data were recorded at 2, 12, 24 and 48h post-CPB. Logistic regression was used to develop a risk prediction model using LCOS as dependent variable. MAIN OUTCOME MEASURES: LCOS, IS, VIS, MR-proADM, cTn-I, age, sex, CPB time, PIM-2, Aristotle score. RESULTS: While statistical significance was not recorded for IS in the multivariate analysis, VIS was seen to be independently associated to LCOS. On the other hand, VIS>15.5 at 2h post-CPB, adjusted for age and CPB timepoints, showed high specificity (92.87%; 95%CI: 86.75-98.96) and increased negative predictive value (75.59%, 95%CI: 71.1-88.08) for the diagnosis of LCOS at 48h post-CPB. The predictive power for LCOS did not increase when VIS was combined with cTn-I >14ng/ml at 2h and MR-proADM >1.5nmol/l at 24h post-CPB. CONCLUSIONS: The VIS score at 2h post-CPB was identified as an independent early predictor of LCOS. This predictive value was not increased when associated with LCOS cardiac biomarkers. The VIS score was more useful than IS post-CPB in making early therapeutic decisions in clinical practice post-CPB.

Characterization of the Glucocorticoid Receptor in Children Undergoing Cardiac Surgery.

OBJECTIVES: Postoperative administration of corticosteroids is common practice for managing catecholamine refractory low cardiac output syndrome. Since corticosteroid activity is dependent on the glucocorticoid receptor, we sought to characterize glucocorticoid receptor levels in children undergoing cardiac surgery and examined the association between glucocorticoid receptor levels and cardiovascular dysfunction. DESIGN: Prospective observational cohort study. SETTING: Large, tertiary pediatric cardiac center. SUBJECTS: Children undergoing corrective or palliative cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A prospective observational cohort study was conducted in 83 children with congenital heart disease. Total glucocorticoid receptor levels were measured in the peripheral WBCs using flow cytometry. In addition, blood samples were collected for total cortisol levels. The primary outcome studied was the time to being inotrope free. An increase in glucocorticoid receptor level from postoperative day 1 to postoperative day 3 was associated with a longer time to being inotrope free (hazard ratio, 0.49 [0.29-0.81]; p = 0.01) in the univariate analysis. This association remained significant after adjusting for age, weight, cardiopulmonary bypass time, cross clamp time, Risk Adjustment for Congenital Heart Surgery-1 score, and postoperative steroid use (hazard ratio, 0.53 [0.29-0.99]; p = 0.05). Postoperative day 3 glucocorticoid receptor level showed a trend to have longer time to being inotrope free (hazard ratio, 0.66 [0.42-1.02]; p = 0.0.06). The cortisol levels minimally increased during the study duration and did not correlate with glucocorticoid receptor levels. CONCLUSIONS: Increasing glucocorticoid receptor levels in peripheral WBCs of children undergoing cardiac surgery are associated with a longer time to being inotrope free. Cortisol levels minimally increased during the study duration. These results suggest that exposure to high-dose perioperative corticosteroids may suppress the hypothalamic-pituitary-adrenal axis leading to increase in glucocorticoid receptor levels in response to a low cortisol environment. Further studies are required to better delineate the interplay between glucocorticoid receptor levels, cortisol levels, corticosteroid exposure, and postoperative inotropic requirements.

Low cardiac output syndrome in the postoperative period of cardiac surgery. Profile, differences in clinical course and prognosis. The ESBAGA study. / Síndrome de bajo gasto cardiaco en el postoperatorio de cirugía cardiaca. Perfil, diferencias en evolución clínica y pronóstico. Estudio ESBAGA.

OBJECTIVES: An analysis is made of the clinical profile, evolution and differences in morbidity and mortality of low cardiac output syndrome (LCOS) in the postoperative period of cardiac surgery, according to the 3 diagnostic subgroups defined by the SEMICYUC Consensus 2012. DESIGN: A multicenter, prospective cohort study was carried out. SETTING: ICUs of Spanish hospitals with cardiac surgery. PATIENTS: A consecutive sample of 2,070 cardiac surgery patients was included, with the analysis of 137 patients with LCOS. INTERVENTIONS: No intervention was carried out. RESULTS: The mean patient age was 68.3±9.3 years (65.2% males), with a EuroSCORE II of 9.99±13. NYHA functional class III-IV (52.9%), left ventricular ejection fraction<35% (33.6%), AMI (31.9%), severe PHT (21.7%), critical preoperative condition (18.8%), prior cardiac surgery (18.1%), PTCA/stent placement (16.7%). According to subgroups, 46 patients fulfilled hemodynamic criteria of LCOS (group A), 50 clinical criteria (group B), and the rest (n=41) presented cardiogenic shock (group C). Significant differences were observed over the evolutive course between the subgroups in terms of time subjected to mechanical ventilation (114.4, 135.4 and 180.3min in groups A, B and C, respectively; P<.001), renal replacement requirements (11.4, 14.6 and 36.6%; P=.007), multiorgan failure (16.7, 13 and 47.5%), and mortality (13.6, 12.5 and 35.9%; P=.01). The mean maximum lactate concentration was higher in cardiogenic shock patients (P=.002). CONCLUSIONS: The clinical evolution of these patients leads to high morbidity and mortality. We found differences between the subgroups in terms of the postoperative clinical course and mortality.

Myocardial protection during minimally invasive cardiac surgery through right mini-thoracotomy.

BACKGROUND: Myocardial damage is an independent predictor of adverse outcome following cardiac surgery and myocardial protection is one of the key factors to achieve successful outcomes. Cardioplegia with Custodiol is currently the most used cardioplegia during minimally invasive cardiac surgery (MICS). Different randomized controlled trials compared blood and Custodiol cardioplegia in the context of traditional cardiac surgery. No data are available for MICS. AIM: The aim of this study was to compare the efficacy of cold blood versus Custodiol cardioplegia during MICS. METHOD: We retrospectively evaluated 90 patients undergoing MICS through a right mini-thoracotomy in a three-year period. Myocardial protection was performed using cold blood (44 patients, CBC group) or Custodiol (46 patients, Custodiol group) cardioplegia, based on surgeon preference and complexity of surgery. RESULTS: The primary outcomes were post-operative cardiac troponin I (cTnI) and creatine kinase MB (CKMB) serum release and the incidence of Low Cardiac Output Syndrome (LCOS). Aortic cross-clamp and cardiopulmonary bypass times were higher in the Custodiol group. No difference was observed in myocardial injury enzyme release (peak cTnI value was 18±46 ng/ml in CBC and 21±37 ng/ml in Custodiol; p=0.245). No differences were observed for mortality, LCOS, atrial or ventricular arrhythmias onset, transfusions, mechanical ventilation time duration, intensive care unit and total hospital stay. CONCLUSIONS: Custodiol and cold blood cardioplegic solutions seem to assure similar myocardial protection in patients undergoing cardiac surgery through a right mini-thoracotomy approach.

Central Venous to Arterial CO2 Difference After Cardiac Surgery in Infants and Neonates.

OBJECTIVES: Venous to arterial CO2 difference correlates with cardiac output in critically ill adults, but its utility in pediatric patients is unclear. We sought to correlate venous to arterial CO2 difference with other cardiac output surrogates (arteriovenous oxygen saturation difference, central venous oxygen saturation, and lactate) and investigate its capacity to predict poor outcomes associated with low cardiac output (low cardiac output syndrome) in infants after cardiac surgery with cardiopulmonary bypass. DESIGN: Retrospective chart review. Poor outcome was defined as any inotrope score greater than 15; death, cardiac arrest, extracorporeal membrane oxygenation; and unplanned surgical reintervention. SETTING: Pediatric cardiovascular ICU. PATIENTS: One hundred thirty-nine infants less than 90 days who underwent cardiopulmonary bypass, from October 2012 to May 2015. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Two hundred ninety-six arterial and venous blood gas pairs from admission (n = 139), 6 (n = 62), 12 (n = 73), and 24 hours (n = 22) were included in analysis. For all pairs, venous to arterial CO2 difference was moderately correlated with arteriovenous oxygen saturation difference (R = 0.53; p < 0.01) and central venous oxygen saturation (R = -0.43; p < 0.01), but not lactate. At admission, venous to arterial CO2 difference was also moderately correlated with central venous oxygen saturation (R = -0.40; p < 0.01) and arteriovenous oxygen saturation difference (R = 0.55; p < 0.01), but not lactate. Thirty-four of 139 neonates (24.5%) had poor outcome. Median admission venous to arterial CO2 difference was 5.9 mm Hg (3.8-9.2 mm Hg). Patients with poor outcome had median admission venous to arterial CO2 difference 8.3 (5.6-14.9) versus 5.4 mm Hg (3.0-8.4 mm Hg) in those without poor outcome. Venous to arterial CO2 difference (area under the curve = 0.69; p < 0.01), serum lactate (area under the curve = 0.64; p = 0.02), and central venous oxygen saturation (area under the curve = 0.74; p < 0.01) were predictive of poor outcome. After controlling for covariates, admission venous to arterial CO2 difference remained significantly associated with poor outcome (odds ratio, 1.3; 95% CI, 1.1-1.45), including independent association with mortality (odds ratio, 1.2; 95% CI, 1.07-1.31). CONCLUSIONS: Venous to arterial CO2 difference is correlated with important surrogates of cardiac output, and is associated with poor outcome and mortality related to low cardiac output syndrome after cardiac surgery in infants. Prospective validation of these findings, including confirmation that venous to arterial CO2 difference can identify low cardiac output syndrome in real time, is warranted.

Identification of prognostic markers in transthyretin and AL cardiac amyloidosis.

BACKGROUND: The prognosis of amyloidosis is known to depend heavily on cardiac function and may be improved by identifying patients at highest risk for adverse cardiac events. AIMS: Identify predictors of mortality in patients with cardiac light-chain amyloidosis (AL), hereditary transthyretin amyloidosis (m-TTR), or wild-type transthyretin amyloidosis (WT-TTR) to prompt physician to refer these patients to dedicated centers. METHODS AND RESULTS: Observational study. About 266 patients referred for suspected cardiac amyloidosis (CA) in two French university centers were included. About 198 patients had CA (AL = 118, m-TTR = 57, and WT-TTR = 23). Their median (25th-75th percentile) age, NT-proBNP left ventricular ejection fraction were, respectively, 68 years (59-76), 2339 pg mL-1 (424-5974), and 60% (48-66). About 31% were in NYHA class III-IV. Interventricular septal thickness was greater in the m-TTR and WT-TTR groups than in the AL group (p < 0.0001). Median follow-up in survivor was 26 months (15-44) and 87 (44%) patients died. By multivariate analysis, independent predictors of mortality for AL amyloidosis were the following: age, cardiac output and NT-proBNP; for TTR amyloidosis was: NT-proBNP. When all amyloidosis were combined NT-proBNP, low cardiac output and pericardial effusion were independently associated with mortality. CONCLUSION: NT-proBNP is a strong prognosticator in the three types of cardiac amyloidosis. High NT-proBNP, low cardiac output, and pericardial effusion at the time of screening should prompt physician to refer the patients to amyloidosis referral center.

Low Cardiac Output Leads Hepatic Fibrosis in Right Heart Failure Model Rats.

BACKGROUND: Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB)-induced right heart failure model and investigated whether cardiac output (CO) is responsible for the progression of hepatic fibrosis. METHODS AND RESULTS: Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2±27.6 and 150.1±31.2 ml/min, P<0.01). Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8±1.7 and 1.0±0.2%, P<0.01, 76.2±27.5 and 32.7±7.5 ng/ml, P<0.01). Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1α positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-ß1, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2) were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1α was significantly increased in the PAB group than that in the control group (2.31±0.84 and 1.0±0.18 arbitrary units, P<0.05). CONCLUSIONS: Our study demonstrated that low CO and tissue hypoxia were responsible for hepatic fibrosis in right failure heart model rats.

Combined Free Light Chains Are Novel Predictors of Prognosis in Heart Failure.

OBJECTIVES: This study investigated the prevalence and potential incremental prognostic value of combined free light chains (cFLCs) in patients recently hospitalized with decompensated heart failure (HF). BACKGROUND: Inflammatory pathways are recognized in the pathogenesis and progression of HF. Free light chain (FLC) elevation is conventionally associated with monoclonal gammopathies, including multiple myeloma. Polyclonal increases in both kappa and lambda FLCs occur in autoimmune and other chronic inflammatory conditions. Recently, a novel assay for measuring kappa and lambda immunoglobulin FLCs together, known as combined free light chain (cFLC) has been developed. METHODS: Six hundred twenty-eight patients recently hospitalized with decompensated HF were studied. cFLCs were measured by turbidimetry using an immunoassay. The incremental prognostic value of cFLCs for mortality was evaluated using Cox proportional hazard models including 22 established predictors of outcome in HF. RESULTS: Of 628 patients, 290 (46%) died during a follow-up of 3.2 ± 1.5 years. Two hundred seventy patients (43%) had elevated cFLCs. There was a clear gradient in the risk of death according to cFLC quartile, with those in the top quartile having an unadjusted risk of mortality more than twice that of those in the lowest quartile (hazard ratio: 2.38; p < 0.0001). After multivariable analysis, cFLC remained an independent predictor of mortality, with an almost 50% higher adjusted risk for those in the top compared with bottom quartile. Older age, lower body mass index, New York Heart Association classification III/IV, previous myocardial infarction, current smoking and B-type natriuretic peptide, bilirubin, high-sensitivity C-reactive protein, glycated hemoglobin, and lymphocyte concentrations were also independent predictors of mortality. CONCLUSIONS: cFLCs are an independent predictor of mortality in patients recently hospitalized with decompensated HF. Further work is required to assess the effects of HF therapies on cFLC concentrations and whether or not directly targeting this marker of inflammation improves prognosis for patients with HF.

Metabolic Uncoupling Following Cardiopulmonary Bypass.

OBJECTIVE: The objective of this study was to characterize the natural history of metabolic uncoupling (type B hyperlactemia and hyperglycemia) following cardiopulmonary bypass (CPB), and to determine the impact of insulin therapy on time to lactate normalization in patients without low cardiac output. DESIGN: The design used was a retrospective cohort study. SETTING: The study was set in a pediatric cardiac intensive care unit in a tertiary-care urban children's hospital. PATIENTS: All patients were aged ≤21 years admitted between 2007 and 2013 following cardiac surgery involving CPB with empiric intraoperative corticosteroids. ELIGIBILITY CRITERIA: simultaneous hyperlactemia (≥3.5 mEq/L) and hyperglycemia (≥200 mg/dL) within 48 hours after bypass. EXCLUSION CRITERIA: Exclusion criteria were evidence of low cardiac output state, diabetes or postoperative steroid administration. INTERVENTIONS: Characteristics were compared between those treated with insulin and those who were not (controls). OUTCOME MEASURES: Outcome measures used were time from admission to onset of hyperglycemia and hyperlactemia and time to resolution. Clinical outcomes included duration of mechanical ventilation, length of stay, unplanned readmission/reoperation, hypoglycemia and death. RESULTS: Of the 1345 patients receiving CPB, 132 (9.8%) met inclusion criteria. Seventy-eight (59%) were treated with insulin, leaving 54 controls. Patient characteristics, surgical complexity and time to onset of hyperglycemia and hyperlactemia were similar between groups. The insulin group had a shorter duration of hyperglycemia. There was no significant difference between groups in time to lactate normalization, ventilator days, length of stay, readmission and reoperation rates. Hypoglycemia (<60 mg/dL) occurred in three patients. CONCLUSIONS: In children with metabolic uncoupling after CPB, insulin use did not shorten the time to lactate normalization or alter clinical outcomes. These findings suggest that type B hyperlactemia with hyperglycemia after CPB will resolve spontaneously and does not warrant specific treatment.

[GDF-15, MRproADM, CTproET1, and CTproAVP in patients with asymptomatic diastolic dysfunction]. / GDF-15, MRproADM, CTproET1 und CTproAVP bei Patienten mit asymptomatischer diastolischer Dysfunktion.

BACKGROUND: The role of biomarkers in asymptomatic diastolic dysfunction (DD) has not been investigated so far. The aim of the study was to evaluate the clinical associations and the diagnostic property of different biomarkers in patients with asymptomatic DD. METHODS: Within a population based observational study, healthy participants (50-85 years) with an LVEF ≥ 50 % and no cardiovascular risk factor were prospectively identified. Patients were classified as having either DD (grade ≥ 1, n = 103) or no DD (CON: n = 85). All patients underwent physical examination including medical history, six-minute-walk-testing, QoL (SF-36), comprehensive echocardiography and blood sampling to measure routine values and specified biomarkers (NTproBNP, MRproANP, GDF-15, MRproADM, CTproET1, CTproAVP). RESULTS: In the DD-group plasma concentration of GDF-15 (p = 0,002), MRproADM (p < 0,001), and CTproAVP (p = 0,003) were significantly higher than in the CON-group. In contrast, NTproBNP (p = 0,390), MRproANP (p = 287), and CTproET1 (p = 0,393) did not differ. GDF-15, MRproADM and CTproAVP were significantly associated with the presence of DD. However, the significance of the seen associations was lost after multiple adjustments. NTproBNP, MRproANP, and MRproADM were significantly related to E / e' as a continuous measure of diastolic function. The significance of the seen associations was lost after multiple adjustments. In ROC analyses, none of the investigated biomarkers was able to relevantly improve the diagnosis of DD. CONCLUSION: In patients with asymptomatic DD plasma concentrations of GDF-15, MRproADM and CT-proAVP were significantly higher when compared with controls. In contrast, NTproBNP, MRproANP and CTproET1 did not differ. After adjustment for age, sex, BMI and renal function, no significant association between DD or E / e' and different biomarkers could be observed. Furthermore, none of the investigated biomarkers was able to substantially improve the diagnosis of DD.

[Evaluation of postoperative myocardial injury by heart-type fatty acid-binding protein in off-pump coronary artery bypass grafting surgery]. / Valoración del daño miocárdico mediante la medición de la heart-fatty acid-binding protein en cirugía de revascularización coronaria sin circulación extracorpórea. Estudio preliminar.

BACKGROUND AND GOAL OF STUDY: Postoperative myocardial infarction is a serious and frequent complication of cardiac surgery. Nonetheless, diagnosis in this context it is occasionally challenging. We sought to evaluate the kinetics and diagnostic accuracy of the new biomarker « heart-type fatty acid-binding protein ¼ (h-FABP) in the early detection of myocardial injury in patients undergoing off-pump coronary artery bypass grafting, compared with classical biomarkers. MATERIALS AND METHODS: A prospective study was conducted on 17 consecutive patients who underwent off-pump coronary artery bypass grafting during a 2 month period. Blood samples were drawn for measurement of myocardial ischemic injury biomarkers (h-FABP, troponin, creatine kinase [CK] and CK-MB), at baseline (T1), immediate post-coronary artery bypass grafting (T2), on ICU admission (T3), and after 4 (T4), 8 (T5), 24 (T6) and 48 h (T7). Perioperative ischemic complications, defined according to electrocardiographic, echocardiographic and hemodynamic criteria, were recorded. RESULTS: Earlier biomarkers peak plasma values occurred at T4 with troponin (2.9 ± 5.2 ng/mL), and at T5 with h-FABP (37.9 ± 55.5 ng/mL). Maximum values of CK and CK-MB occurred later, both in T6 (741 ± 779 and 37 ± 51 U/L, respectively). The optimized cut-off obtained for h-FABP was 19 ng/mL, providing a sensitivity and specificity of 77 and 75%, respectively, for diagnosis of perioperative ischemic injury, with an area under the ROC curve for h-FABP of 0.83 (95% CI 0.6-1.0) vs. 0.63 (95% CI 0.33-0.83) for troponin. This cut-off value for h-FABP is reached on average at T2 (mean value of h-FABP at T2: 18.9 ± 21.5 ng/mL). CONCLUSION: This is the first study evaluating the kinetics of h-FABP biomarker in perioperative off-pump coronary artery bypass grafting, and the cut-off value established could help to extend earlier detection of myocardial ischemia in this context.

Clinical utility of B-type natriuretic peptide (NP) in pediatric cardiac surgery--a systematic review.

BACKGROUND: NP is a biomarker that has been used in the diagnosis, management, and prognostication of a number of cardiovascular disorders in the pediatric population. The physiological role of this hormone is to allow the myocardium to adapt to stress or strain imposed by a volume and/or pressure load. OBJECTIVE: The aim of this study was to determine the utility of preoperative and postoperative NP to predict outcome in pediatric patients undergoing cardiac surgery for structural congenital heart disease. METHOD: We conducted a systematic review by searching three electronic databases using the search terms 'paediatric' or 'pediatric' and 'B-type natriuretic peptide'. Twenty peer-reviewed papers were included in the study. RESULTS: Preoperative NP levels were associated with the severity of cardiac failure in several studies. Preoperative NPs also correlated with early postoperative outcome measures such as duration of cardiopulmonary bypass, duration of mechanical ventilation, presence of low cardiac output syndrome, length of stay in the intensive care unit and in one study, death. Early (within 24 h) postoperative NPs showed a stronger correlation than preoperative NPs to early postoperative adverse events. CONCLUSION: NPs provide a simple, noninvasive and complementary tool to echocardiography that can be used to assist clinicians in the assessment and management of pediatric patients with congenital heart disease in the perioperative period.

Low cardiac output stimulates vasopressin release in patients with stage d heart failure.

BACKGROUND: Depressed hemodynamics stimulates arginine vasopressin (AVP) release, but the relationship between plasma AVP levels (P-AVP) and cardiac parameters, especially in patients with stage D heart failure (HF) receiving guideline-directed medical therapy, has not examined. METHODS AND RESULTS: Data including P-AVP were obtained from 162 in-hospital patients with stage D HF and from 80 patients receiving ventricular assist device (VAD, n=46) or heart transplantation (HTx, n=34) at 3 months after surgery. In the HF group, considerably high P-AVP (5.9±6.1 pg/ml) negatively correlated with serum sodium concentration (S-Na, 135.3±5.8 mEq/L, r=-0.548 [P<0.01]) and cardiac index (CI, 2.2±0.5 L·min(-1)·m(-2), r=-0.458 [P<0.01]). After VAD/HTx treatment, improvement in the CI (2.7±0.5 L·min(-1)·m(-2)[P<0.01] vs. HF) was accompanied by normalization of serum sodium concentration (S-Na; 138.2±2.0 mEq/L [P<0.01] vs. HF) and suppressed release of AVP (1.7±3.4 pg/ml [P<0.01] vs. HF). P-AVP positively correlated with only S-Na (r=0.454 [P<0.01]), whereas no correlation was observed with CI after VAD/HTx treatment. P-AVP ≥5.3 pg/ml well predicted poor 2-year survival in HF group (60% [P<0.01] vs. 90%). CONCLUSIONS: Low cardiac output stimulates AVP release via a non-osmotic process that results in hyponatremia and poor prognosis in patients with stage D HF. After sufficient recovery of cardiac output by cardiac replacement therapy, AVP release is suppressed and is mainly regulated by serum osmolality.

Natriuretic peptides in heart failure with preserved ejection fraction.

Timely diagnosis, early introduction of appropriate treatment, accurate risk stratification, and optimal titration of therapy are all key to the management of acute and chronic heart failure (HF). Plasma concentrations of the cardiac natriuretic peptides (NPs) are valuable aids in each of these elements of care. However, most data are derived from cohorts with undifferentiated HF or HF with reduced ejection fraction (HFREF), and the performance and best application of NPs in HF with preserved ejection fraction (HFPEF) is less certain. This review outlines the evidence for use of NPs in the evaluation and management of HFPEF.

Diagnostic accuracy of central venous saturation in estimating mixed venous saturation is proportional to cardiac performance among cardiac surgical patients.

PURPOSE: Advanced hemodynamic monitoring in cardiac surgery translates into improvement in outcomes. We evaluated the relationship between central venous (ScvO2) and mixed venous (SvO2) saturations over the early postoperative period. The adequacy of their interchangeability was tested in patients with varying degrees of cardiac performance. METHODS: In this prospective observational study, we evaluated 156 consecutive cardiac surgical patients in an academic center. The ScvO2 and SvO2 data were harvested from 468 paired samples taken preoperatively (T0), after weaning from cardiopulmonary bypass (T1) and on postoperative day 1 (T2). RESULTS: The relationship between ScvO2 and SvO2 was inconsistent, with inferior correlations in patients with lower cardiac indices (CI) (Pearson r(2) = 0.37 if CI ≤2.0 L/min per square meter vs r(2) = 0.73 if CI >2.0 L/min per square meter, both P < .01). Patients with lower CI also had wider 95% limits of agreement between SvO2 and ScvO2. The proportion of patients with a negative SvO2-ScvO2 gradient increased over time (48/156 [31%] at T0 to 73/156 [47%] at T2; P < .01). This subgroup more frequently required inotropes at T2 than patients with a positive SvO2-ScvO2 gradient (odds ratio, 6.46 [95% confidence interval, 0.81-51.87], P = .06) and also had higher serum lactate levels (1.5 ± 0.8 vs 1.0 ± 0.4; P < .01). CONCLUSIONS: The diagnostic accuracy of ScvO2 for estimating SvO2 is proportional to cardiac performance. A negative SvO2-ScvO2 gradient at T2 correlated with inotropic support requirement, higher operative risk score, age, lactate level, and duration of cardiopulmonary bypass.

Blood lactate level during extracorporeal life support as a surrogate marker for survival.

OBJECTIVE: The establishment of reliable markers to monitor adequate tissue perfusion during extracorporeal life support is clinically important to improve outcomes. METHODS: We evaluated 115 consecutive adult patients (aged 61.7 ± 13.4 years, 59 female patients) undergoing extracorporeal life support to manage low cardiac output syndrome after major cardiac surgery. The blood lactate levels serially measured during extracorporeal life support (at 6, 12, and 24 hours) were analyzed. RESULTS: Forty-seven patients (40.8%) were weaned off extracorporeal life support successfully, and 32 patients (27.8%) survived to discharge. On logistic regression analysis, a high blood lactate level before extracorporeal life support (relative risk [RR], 1.19; 95% confidence interval [CI], 1.06-1.34) and cardiopulmonary bypass weaning failure after surgery (RR, 4.39; 95% CI, 1.44-13.35) emerged as baseline risk factors of mortality. After adjustment with these factors, blood lactate levels at 6 hours (RR, 1.24; 95% CI, 1.06-1.46), 12 hours (RR, 1.35; 95% CI, 1.10-1.67), and 24 hours (RR, 1.46; 95% CI, 1.10-1.93) were predictive of mortality. When the predictive values of serial blood lactate levels for mortality were assessed using the receiver operating characteristic method, the greatest accuracy was obtained at cutoff values of 7.05 mmol/L at 6 hours (sensitivity, 75.5%; specificity, 75.0%), 4.95 mmol/L at 12 hours (sensitivity, 70.4%; specificity, 76%), and 4.15 mmol/L at 24 hours (sensitivity, 62%; specificity, 93.1%). CONCLUSIONS: Blood lactate measurement can be used as a reliable tool for monitoring adequate tissue perfusion during extracorporeal life support and was strongly predictive of mortality. Therefore, in patients without adequate decrement in lactate levels during extracorporeal life support, potential factors responsible for inadequate perfusion should be identified and corrected.

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.