Prenatal ABO/RHD Genotyping: A New Paradigm to Allow for Fresh Whole Blood for Cardiopulmonary Bypass in the Immediate Newborn Period.

Compared to standard component therapy, fresh whole blood (FWB) offers potential benefits to neonates undergoing cardiopulmonary bypass (CPB) in the context of open cardiac surgery: decreased blood loss and subsequent risk of volume overload, improved coagulation status, higher platelet counts during and following CPB, circumvention of limited vascular access, and significantly reduced donor exposures. Obtaining FWB, however, entails 2-5 days of preparation, which often precludes its availability for neonates requiring CPB in the immediate newborn period. Using a multidisciplinary approach and molecular ABO/RHD genotyping on amniotic fluid, we developed a protocol to allow procurement of FWB for timed delivery followed by open cardiac surgery. Eligible subjects include patients undergoing genetic amniocentesis following the diagnosis of a fetal cardiac anomaly likely to require open surgical repair in the initial days after birth. This protocol has been successfully implemented following prenatal diagnosis of severe fetal cardiac anomalies. Taking advantage of the prenatal time period and the ability to perform fetal blood typing prenatally using molecular genotyping makes possible a new paradigm for the availability of FWB for CPB to improve perioperative, short-term, and long-term outcomes in a population comprised of some of the smallest and sickest patients who will undergo CPB.

Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

INTRODUCTION: Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them. METHODS: Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class. RESULTS: Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class. CONCLUSION: NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients.

Arterial Switch Operation and Plasma Biomarkers: Analysis and Correlation with Early Postoperative Outcomes.

The aims of our study were to describe plasma brain natriuretic peptide (BNP), Troponin I (TnI), and Cystatin C (Cys-C) concentration kinetics in the postoperative period after arterial switch operation in neonate, and to test the correlation between the plasma biomarkers and early clinical outcomes. We prospectively enrolled 29 neonates who underwent ASO. All patients received Custodiol cardioplegia. Blood samples were collected preoperatively (one day before) and in the ICU immediately after admission, and then 6, 12, 24, and 48 h after surgery. TnI peak (mean 17.23 ± 7.0 ng/mL) occurred between the arrival in the ICU and the 6th hour, then we had a constant decrease. TnI had a good correlation with the inotropic support time (r = 0.560, p = 0.0015) and ICU time (r = 0.407, p = 0.028), less than with ventilation and Hospital stay (r = 0.37, p = 0.0451 and r = 0.385, p = 0.0404). BNP peak (mean 4773.79 ± 2724.52 ng/L) was in the preoperative time with a constant decrease after the operation and it had no significant correlations with clinical outcomes. The CyS-C had the highest preoperative values, which decreased during the operating phase, and then constantly increased upon arrival to the ICU with a peak at 48 h (mean 1.76 ± 0.35 mg/L). CyS-C peak had a good correlation with a plasmatic creatinine peak (r = 0.579, p = 0.0009) but not with other clinical outcomes. Our study demonstrated significant correlations between the Tnl peak and early clinical outcomes in neonates undergoing arterial switch operation. Other plasma biomarkers such as the BNP and CyS-C had no direct correlation.

Prognostic Value of Plasma B-Type Natriuretic Peptide in the Long-Term Follow-up of Patients With Transposition of the Great Arteries With Morphologic Right Systemic Ventricle After Atrial Switch Operation.

BACKGROUND: B-type natriuretic peptide (BNP) is an established marker for heart failure assessment, but the prognostic quality of BNP after atrial switch operation (ASO) has not yet been elucidated. METHODS AND RESULTS: In 89 patients (median age, 24 years; range, 15-35 years) after ASO, BNP was measured. During a 48-months follow-up we focused on critical cardiac events, defined as decompensation, sudden cardiac death or need for heart transplantation. BNP was considerably lower in 81 patients in functional class (FC) I/II (median, 35 pg/ml; range, 3-586 pg/ml) than in 6 patients in FC III/IV (median, 246 pg/ml; range, 14-1,150 pg/ml, P≤0.073). BNP was significantly higher after Mustard than after Senning procedure (P≤0.030). There was no significant difference in BNP between simple or complex transposition of the great arteries (TGA) (P≤0.44). Eleven subjects (13%, 95% CI: 7-22%) had a critical cardiac event within 48 months. On ROC analysis BNP had a high predictive value regarding discrimination of patients with and without critical events (area under the ROC curve, 0.90; 95% CI: 0.76 to >0.99, P<0.001). The cut-off was 85 pg/ml (sensitivity, 88%; specificity, 85%). Additionally, estimated event-free-survival was longer after Senning than after Mustard procedure (P≤0.017). There was no significant difference in outcome between patients with simple or complex TGA with regard to occurrence of critical events. CONCLUSIONS: BNP is a sensitive and specific prognostic marker for critical cardiac events after ASO.

Myocardial blood flow in patients with transposition of the great arteries ­ risk factor for dysfunction of the morphologic systemic right ventricle late after atrial repair.

BACKGROUND: Dysfunction of the morphologic systemic right ventricle (RV) is a sequela in long-term survivors with transposition of the great arteries (TGA) after atrial switch operation (AtSO). Impairment of myocardial blood flow (MBF) and coronary flow reserve (CFR) are hypothesized as predisposing factors. METHODS AND RESULTS: The study group comprised 20 patients after AtSO (22.7 ± 5.03 years) and 15 individuals with congenitally corrected transposition (ccTGA) (30.6 ± 19.4 years). MBF was quantified by positron emission tomography; controls for coronary flow were 11 healthy volunteers (26.2 ± 5.1 years). Exercise capacity, ventricular mass, function and end-diastolic volume assessed by coronary magnetic resonance (CMR), hemodynamic parameters assessed by cardiac catheterization and echocardiography, and B-type natriuretic peptide levels correlated with MBF. At rest, MBF did not differ between patients and healthy volunteers (MBFrestml·100 g(-1)·min(-1); ccTGA: 75 ± 14 vs. AtSO: 73 ± 16 vs. controls: 77 ± 15; NS). After vasodilatation, MBF increased significantly, but was significantly lower in ccTGA and AtSO groups compared with controls (MBFstressml·100 g(-1)·min(-1); ccTGA: 198 ± 38 vs. AtSO: 167 ± 46 vs. controls 310 ± 74; P<0.001). In ccTGA, CFR correlated significantly with clinical, CMR, echocardiographic and hemodynamic parameters, but for AtSO patients no significant correlation could be calculated. CONCLUSIONS: In patients with ccTGA, maximal coronary blood flow is attenuated and significantly correlated with ventricular function, whereas dysfunction of the morphologic systemic RV after AtSO is a multifactorial problem.

Impact of novel balloon catheter on static balloon atrial septostomy with double balloon technique in infants with congenital heart disease.

BACKGROUND: The aim of this study was to investigate the feasibility of static balloon atrial septostomy (BAS) with the double balloon technique for infants. TMP PED balloon catheter, newly designed for static BAS in small children, was used in 3 infants. The balloon catheter has a low profile, short and round shoulder, and smooth deflation without slippage. METHODS AND RESULTS: Three infants (transposition of the great arteries, n=2; pulmonary atresia with intact ventricular septum, n=1) underwent static BAS with double balloon for restrictive interatrial communication between December 2014 and March 2015. Hemodynamic and echocardiographic assessment was done before and after the procedure. Pressure gradient between left and right atrium decreased from 6, 7 and 9 mmHg to 2, 2 and 1 mmHg, respectively. Oxygen saturation in systemic artery increased from 72, 68 and 73% to 78, 70 and 79%, respectively. Maximum defect diameter increased from 3.5, 3.0 and 3.3 mm to 6.6×5.2, 9.0×6.2 and 8.1×5.1 mm, respectively. No complication was recorded. CONCLUSIONS: Static BAS with double balloon technique using the novel TMP PED balloon catheter was safe and effective in producing sufficient interatrial communication for 8-20 weeks in infants. Static BAS is a promising procedure to create interatrial communication in infants.

NT-proBNP levels and their relationship with systemic ventricular impairment in adult patients with transposition of the great arteries long after Mustard or Senning procedure.

BACKGROUND: The aim of the study was to investigate serum NT-proBNP levels in adult patients with transposition of the great arteries (d-TGA) corrected by atrial switch procedures (Mustard or Senning) operation and to assess the relationship with ventricular impairment and NYHA class. METHODS: Serum NT-proBNP levels were measured in a group of 81 consecutive adult patients (59 males, mean age 27 years and 22 females, mean age 28 years) with transposition of the great arteries (TGA) after surgical correction in childhood, and in a control group of 25 healthy individuals (16 males, mean age 32 years, and 9 females, mean age 29 years). Age-matched correlation of NT-proBNP concentrations in TGA patients after Mustard or Senning correction was performed, but this correlation was considered not significant (p=0.08). RESULTS: Concentrations of NT-proBNP in patients with TGA were significantly elevated compared to the control group of healthy individuals (203 ng/L vs. 41 ng/L, p<0.0001). Patients after the Mustard repair had significantly higher NT-proBNP values than patients after the Senning operation (234 ng/L vs. 148 ng/L, p=0.0023). NT-proBNP correlated negatively with the systemic right ventricular ejection fraction with the greatest significance in patients after Mustard correction (r=-0.32, p<0.0001). The concentration of NT-proBNP was also associated with NYHA functional class (p=0.0035) with the greatest significance in patients with Mustard correction (p=0.028). CONCLUSIONS: Elevated levels of NT-proBNP appear to be a useful tool in assessing heart failure in patients with transposition of the great arteries after atrial switch correction.

Preoperative factors as a predictor for early postoperative outcomes after repair of congenital transposition of the great arteries.

Transposition of the great arteries (TGA) requires early surgical repair during the neonatal period. Several preoperative factors have been identified for the postoperative poor outcome after arterial switch operation (ASO). However, the data remain uncertain an association. Therefore, we investigated the preoperative factors which affect the early postoperative outcomes. Between March 2005 and May 2012, a retrospective study was performed which included 126 infants with an ASO for TGA. Preoperative data included the vasoactive inotropic score (VIS) and baseline hemodynamics. Early postoperative outcomes included the duration of mechanical ventilation, the length of stay in the intensive care unit and hospital, and early mortality. Multivariate linear regression and receiver operating characteristics analysis were performed. The duration of mechanical ventilation was significantly correlated with the preoperative mechanical ventilator support and VIS, and CPB time. On multivariate linear regression analysis, a higher preoperative VIS, preoperative B-type natriuretic peptide (BNP) level, and the CPB time were identified as independent risk factors for delayed mechanical ventilation. Preoperative VIS (OR 1.154, 95 % CI 1.024-1.300) and the CPB time (OR 1.034, 95 % CI 1.009-1.060) were independent parameters predicting early mortality. A preoperative VIS of 12.5 had the best combined sensitivity (83.3 %) and specificity (85.3 %) and an AUC of 0.852 (95 % CI 0.642-1.061) predicted early mortality. Our results suggest that preoperative VIS and BNP can predict the need for prolonged postoperative mechanical ventilation. Moreover, preoperative VIS may be used as a simple and feasible indicator for predicting early mortality.

[Cellular and biochemical contents of suspension of the laundered autologous erythrocytes, obtained using a cell saver apparatus].

Efficacy of autologous blood and residual blood laundering while cardiosurgical operations performance in a newborn babies for the inborn heart failures in conditions of artificial blood circulation, using a cell saver apparatus, was investigated. In accordance to the investigation data obtained, the efficacy of a free hemoglobin laundering have constituted 71.6%, proinflammatory interleukin-6--95.8%, loss of thrombocytes--85.8%.

Circulating microRNA expression profile and systemic right ventricular function in adults after atrial switch operation for complete transposition of the great arteries.

BACKGROUND: Data on the use of circulating microRNAs (miRNAs) as biomarkers of cardiovascular diseases are emerging. Little, however, is known on the expression profile of circulating of microRNAs in congenital heart malformations with a systemic right ventricle that is prone to functional impairment. We aimed to test the hypothesis that circulating miRNA profile is altered in patients late after atrial switch operation for complete transposition of the great arteries (TGA) and further explored possible relationships between alteration of circulating miRNAs and systemic ventricular contractility. METHODS: Circulating miRNA expression profiling of serum samples from 5 patients and 5 healthy controls was performed. The results were validated in 26 patients and 20 controls using real-time quantitative reverse-transcription polymerase chain reaction for candidate miRNAs with fold changes >3 by expression profiling. Systemic ventricular myocardial acceleration during isovolumic contraction (IVA) was determined by colour tissue Doppler echocardiography. RESULTS: Compared with controls, patients had significantly lower systemic ventricular IVA (p = 0.002). Of the 23 upregulated miRNAs identified by profiling, 11 were validated to be increased in patients compared with controls: miR-16, miR-106a, miR-144*, miR-18a, miR-25, miR-451, miR-486-3p, miR-486-5p, miR-505*, let-7e and miR-93. Among the validated 11 miRNAs, miR-18a (r = -0.45, p = 0.002) and miR-486-5p (r = -0.35, p = 0.018) correlated negatively with systemic ventricular IVA for the whole cohort. CONCLUSIONS: A distinct serum miRNA expression signature exists in adults with complete TGA after atrial switch operation, with serum miR-18a and miR-486-5p being associated with systemic ventricular contractility.

Exercise training improves exercise capacity in adult patients with a systemic right ventricle: a randomized clinical trial.

OBJECTIVE: To assess whether exercise training in adult patients with a systemic right ventricle (RV) improves exercise capacity and quality of life and lowers serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels. DESIGN: Multi-centre parallel randomized controlled trial. PARTICIPANTS: Patients with a systemic RV due to congenitally or surgically corrected transposition of the great arteries. METHODS: Fifty-four adult patients with a systemic RV, were randomized using unmarked opaque envelopes to an intervention group (n = 28) with three training sessions per week for 10 consecutive weeks, and a control group (n = 26). Randomization was stratified by participating centre. At baseline, and follow-up, we determined maximal exercise capacity (V'O(2peak)), serum NT-proBNP levels, and quality of life by means of the SF-36, and the TAAQOL Congenital Heart Disease questionnaires. The final analysis was performed by linear regression, taking into account the stratified randomization. RESULTS: Forty-six patients were analysed (male 50%, age 32 ± 11 years, intervention group n = 24, control group n = 22). Analysis at 10 weeks showed a significant difference in V'O(2peak) (3.4 mL/kg/min, 95% CI: 0.2 to 6.7; P = 0.04) and resting systolic blood pressure (-7.6 mmHg, 95% CI: -14.0 to -1.3; P = 0.03) in favour of the exercise group. No significant changes were found in serum NT-proBNP levels or quality of life in the intervention group or in the control group nor between groups. None of the patients in the intervention group had to discontinue the training programme due to adverse events. CONCLUSION: In adult patients with a systemic RV exercise training improve exercise capacity. We recommend to revise restrictive guidelines, and to encourage patients to become physically active. ( TRIAL REGISTRATION: The study was registered at http://trialregister.nl. Identifier: NTR1909.).

Galectin-3 plasma levels in adult congenital heart disease and the pressure overloaded right ventricle: reason matters.

Aim: To assess galectin-3 (Gal-3) levels and their relationship with clinical status and right ventricular (RV) performance in adults with RV pressure overload of various mechanisms due to congenital heart disease. Materials & methods: A cross-sectional study was conducted. Patients underwent clinical examination, blood testing and transthoracic echocardiography. Results: The study included 63 patients with congenitally corrected transposition of the great arteries, 41 patients with Eisenmenger syndrome and 20 healthy controls. Gal-3 concentrations were higher in patients compared with controls (7.83 vs 6.11 ng/ml; p = 0.002). Biomarker levels correlated with age, New York Health Association class, N-terminal probrain natriuretic peptide and RV function only in congenitally corrected transposition of the great arteries patients. Conclusion: Gal-3 profile in congenital heart disease patients and pressure-overloaded RV differs according to the cause of pressure overload.

Myocardial protection in the arterial switch operation: Custodiol versus cold blood cardioplegia.

OBJECTIVES: The optimal myocardial protective solution in the neonatal arterial switch operation remains controversial. The aim of this study was to demonstrate that Bretschneider's histidine-tryptophan-ketoglutarate crystalloid solution (Custodiol) offers protection at least similar to that of cold blood cardioplegia. METHODS: Patients who underwent the neonatal arterial switch operation with Custodiol between January 2016 and December 2018 (n = 23) were compared with an historical cohort from August 2010 to December 2015 in which cold blood cardioplegia was used (n = 41). A linear mixed-effect model for repeated measures was performed to test the recovery of myocardial function based on inotropic and vasoactive inotropic scores, cardiac enzyme release and left ventricular ejection fraction. RESULTS: Patients in the cold blood cardioplegia group had higher inotropic scores in the first 24 h (0 h, P = 0.001 and 24 h, P = 0.006) and higher vasoactive inotropic scores in the first 72 h (0 h, 24 h and 48 h, P < 0.001; 72 h, P = 0.012). Cardiac troponin-I concentrations were higher in the cold blood cardioplegia group at postoperative hours 1-72 (1 h, 6 h, 12 h and 24 h, P < 0.001; 48 h, P = 0.001 and 72 h, P = 0.003). Creatinine-kinase-MB concentrations were higher in the cold blood cardioplegia group at postoperative hours 1-24 (1 h, 6 h and 12 h, P < 0.001; 24 h, P = 0.042). The left ventricular ejection fraction was higher in the Custodiol group just after the operation (P = 0.005), at 24 h (P = 0.001) and on the first day without inotropic support (P = 0.011). CONCLUSIONS: Neonatal myocardium protected with Custodiol during the arterial switch operation presented optimal ventricular function recovery with less inotropic support and less myocardial damage compared with cold blood cardioplegia.

Early discontinuation of intravenous prostaglandin E1 after balloon atrial septostomy is associated with an increased risk of rebound hypoxemia.

OBJECTIVE: A comparison of the effects of early (<2 h) and late (>or=2 h) discontinuation of prostaglandin E1 (PGE1), on systemic oxygenation following a successful balloon atrial septostomy (BAS), in neonates with confirmed diagnosis of d-transposition of the great arteries (d-TGA). STUDY DESIGN: Neonates with a postnatal diagnosis of d-TGA who were admitted to a quaternary neonatal intensive care unit between January 1999 and December 2004 were identified from the local database. The effects of time of discontinuation of PGE1 on oxygen saturations, oxygen requirement, need for reinstitution of prostaglandin infusion and postoperative stability were analyzed. RESULT: Sixty neonates with a diagnosis of d-TGA were identified, 45 of whom had a BAS performed. Of these, 25 cases had early (<2 h) discontinuation of PGE1 whereas in the remaining 20 discontinuation was late (>or=2 h). PGE1 infusion was recommenced in 20 neonates (20/45 (44%)) after a successful BAS due to rebound hypoxemia. Of these, there was a threefold increase in the need for reinstitution of prostaglandin in the early compared to late discontinuation group (16/25 (64%) vs 4/20 (20%), P<0.006). There was no difference in postoperative cardiorespiratory stability. CONCLUSION: Early discontinuation of intravenous PGE1 following BAS was associated with an increased risk of rebound hypoxemia, necessitating the recommencement of PGE1. We speculate the rapid improvement in oxygenation on reinstitution of PGE1 is secondary to pulmonary vasodilation and improved pulmonary blood flow. We propose a more cautious and graded approach to discontinuation of PGE1 based on illness severity and the magnitude and duration of hypoxemia at presentation.

The syndrome of cardiac failure in adults with congenitally corrected transposition.

OBJECTIVES: To assess neurohormonal activation of cardiac failure in adults with congenitally corrected transposition, and to determine the most sensitive marker for recognition of the cardiac failure. BACKGROUND: The onset of morphologically right ventricular dysfunction is unpredictable in patients with congenitally corrected transposition, the combination of discordant atrioventricular and ventriculo-arterial connections, and its markers are unknown. METHODS: We measured amino terminal pro brain natriuretic peptide in 19 patients, aged 35 plus or minus 13.1 years, and in 19 control subjects. Morhologically right ventricular function was assessed by echocardiography, including tissue Doppler echocardiography and magnetic resonance imaging or multislice computed tomography. RESULTS: The patients showed a highly significant increase in the levels of amino terminal pro brain natriuretic peptide, the levels being significantly elevated even in asymptomatic patients. Left atrial dimensions were larger in patients, and significantly lower tissue Doppler echocardiographic velocities were measured at the lateral site of the tricuspid annulus and at the basal segment of the interventricular septum. The ejection fraction of the morphologically right ventricle correlated significantly with the levels of brain natriuretic peptide, and with left atrial dimensions. CONCLUSIONS: Neurohormonal activation is present in patients with congenitally corrected transposition even when they are asymptomatic. It is correlated with left atrial dimensions and tissue Doppler echocardiographic parameters. Levels of brain natriuretic peptide, and peak tricuspid early diastolic annular velocity, are the earliest and most sensitive markers of morphologically right ventricular dysfunction.

Role of myocardial collagen degradation and fibrosis in right ventricle dysfunction in transposition of the great arteries after atrial switch.

BACKGROUND: Heart failure is a serious event in patients with transposition of the great arteries (D-TGA) after atrial redirection surgery. We aimed to determine the association between myocardial fibrosis and systolic and diastolic systemic right ventricle (sRV) dysfunction. METHODS: Diastolic and systolic function of sRV was prospectively assessed using echocardiography and cardiac magnetic resonance imaging (CMR) in 48 patients with atrially switched D-TGA and 26 healthy subjects. Diastolic function of the subaortic ventricle was assessed by echocardiography Doppler and DTI. In CMR, ejection fraction of sRV and wall stress defined as the product of the systolic blood pressure and volume/mass ratio were assessed. Fibrosis extent within sRV myocardium was evaluated using gadolinium-enhanced magnetic resonance and serum collagen turnover biomarkers. RESULTS: Late gadolinium enhancement (LGE) was found in 35% of D-TGA patients, and the collagen degradation biomarker pro-MMP1:TIMP1 ratio was significantly increased in D-TGA patients compared to healthy subjects (1.0 × 10-2vs. 2.5 × 10-2, p = 0.04). Increase in sRV wall stress was significantly associated with LGE (p = 0.01) and pro-MMP1:TIMP1 ratio (r = 0.77, p < 0.01). After adjustment for age, sex, BMI, blood pressure and cardiac treatment, pro-MMP1:TIMP1 ratio was the strongest determinant of sRVEF (R2 = 0.85, p < 0.01). Pro-MMP1:TIMP1 ratio was also significantly correlated with the early diastolic filling parameter E/E' (r = 0.53, p = 0.02), but this was not anymore the case after adjustment. CONCLUSIONS: Diastolic and systolic sRV dysfunction is related to myocardial collagen degradation and fibrosis. Research in medical therapies that reduce systemic sRV afterload and limit collagen degradation is warranted in this setting.

High sensitivity cardiac troponin T and systemic right ventricular function in adults with congenitally corrected transposition of the great arteries.

BACKGROUND: High sensitive troponin T (hsTnT), a marker of myocardial injury, appears to be a promising diagnostic tool in patients with congenital heart disease. However, little is known about its distribution among adults with systemic right ventricle (sRV). We aimed to assess the distribution of hsTnT concentrations in patients with congenitally corrected transposition of the great arteries (ccTGA) and to evaluate its relationship with sRV function and NT-proBNP. METHODS: A cross-sectional study of adults with ccTGA was conducted. Patients underwent transthoracic echocardiography, hs-TnT and NTproBNP measurements. In the echocardiographic study, the sRV function was assessed qualitatively and quantitatively using fractional area change (FAC), TAPSE, myocardial performance index (MPI), systolic pulsed Doppler velocity (s') and global longitudinal strain (GLS. RESULTS: Fifty patients with ccTGA (20F/30M) and a mean age of 34.8±13.6years (range 18-63years) were included, with 27 of them (54%) having detectable hsTnT. Patients with detectable hsTnT were older and more often had NYHA class>I. Detectable hsTnT was associated with lower FAC (0.35 vs. 0.41, p<0.01) and GLS (-14.4% vs. -17.8%, p<0.01)) and higher MPI (0.67 vs. 0.48, p<0.01)). Hs-TnT correlated weekly with NT-proBNP (r=0.38; p<0.001). The area under the curve for the detection of sRV dysfunction (FAC<0.35) was higher for hs-TnT (0.839; CI 0.713-0.952) than for NT-proBNP (0.709; CI 0.545-0.873). CONCLUSION: HsTnT was detectable in over half of the ccTGA population and was related to the sRV function. Compared to NTproBNP, hsTnT level seems to be superior biomarker in discriminating patients with sRV dysfunction.

Assessment of systemic right ventricular function in adult overweight and obese patients with congenitally corrected transposition of the great arteries.

BACKGROUND: In congenitally corrected transposition of the great arteries the right ventricle (RV) supports systemic circulation, and patients are prone to develop heart failure over time. Chronic volume overload secondary to obesity may contribute to premature dysfunction of the systemic RV. AIM: The aim of our study was to assess the systemic RV function in overweight/obese adult patients with congenitally corrected transposition of the great arteries. METHODS: Transthoracic echocardiographic studies and laboratory testing (N-terminal pro-B-type natriuretic peptide [NT-proBNP] assessment) were performed in patients with congenitally corrected transposition, who were scheduled for a routine examination, and the body mass index was calculated for each patient. RESULTS: We studied 56 adults (31 men; mean age 33.9 years); 22 of whom were overweight (body mass index [BMI] of 25-29.9 kg/m²) or obese (BMI of 30 kg/m² or more), and 34 of whom were normal weight (BMI below 25 kg/m²). Age, gender, heart rate, and blood pressure were similar in both groups. The mean NT-proBNP levels were not significantly different. On echocardiography, the overweight/obese patients had a decreased systemic RV fractional area change (0.38) compared to normal weight patients (0.43); p = 0.02. Moreover, a significant reduction in the global longitudinal strain in the overweight/obese group was observed (-15.3% vs. -18.3%; p = 0.01). CONCLUSIONS: Overweight/obesity in adult patients with congenitally corrected transposition of the great arteries is associated with impaired systemic RV function.

NT-proBNP predicts mortality in adults with transposition of the great arteries late after Mustard or Senning correction.

OBJECTIVE: The patients after Mustard and Senning corrections of transposition of the great arteries (TGA) are at an increased risk of unexpected death. The aim of this study was to identify markers allowing risk stratification of patients after atrial switch correction of TGA to provide them with optimum care. METHODS AND RESULTS: In this study, 87 patients were retrospectively evaluated after atrial switch correction of TGA followed-up between 2005 and 2015. The mortality during the follow-up was 9% (8 cardiac deaths). Markers significantly predictive of death using univariable Cox proportional hazard ratio survival analysis were: N-terminal pro-B-type natriuretic peptide (NT-proBNP), ejection fraction and end-diastolic dimension of the systemic right ventricle, mitral E, e', and s'. Surprisingly, the Doppler parameters of mitral valve in subpulmonary ventricle were more important for prognosis than those of systemic tricuspid valve. In multivariable analysis, the only independent predictors of mortality were NT-proBNP (P = .00048; AUC 0.97) and the velocity of early diastolic filling (mitral E) in subpulmonary ventricle (P = .01815; AUC 0.81). According to Kaplan-Meier survival analysis, patients with NT-proBNP > 1000 pg/ml are at high risk of death. Patients with mitral E < 68 cm/s are also at an increased risk of death. CONCLUSIONS: NT-proBNP is the most reliable prognostic mortality factor and should be measured regularly in TGA patients after Mustard or Senning correction. Diastolic filling velocity of the subpulmonary left ventricle (mitral E) may be more important for prognosis than systolic function of the systemic right ventricle.

Collagen turnover biomarkers and systemic right ventricle remodeling in adults with previous atrial switch procedure for transposition of the great arteries.

BACKGROUND: Myocardial fibrosis is a potential pathophysiological mechanism leading to systemic right ventricular (SRV) deterioration. We hypothesize that circulating levels of collagen deposition markers are elevated in patients with SRV remodeling and this elevation may have a predictive value. METHODS: We prospectively evaluated 56 patients with D-TGA after the atrial switch procedure (mean age 25.6 ± 4.8, range 18-37 years; 67% males). Serum levels of procollagen type III amino-terminal propeptide (PIIINP), collagen type I carboxy-terminal telopeptide (CITP), procollagen type I N-terminal propeptide (PINP), matrix metalloproteinase (MMP 1, MMP 9) and a tissue inhibitor of matrix metalloproteinase (TIMP 1) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) were measured and compared with healthy controls. The relationship between these serum markers, echocardiographic and cardiac magnetic resonance parameters and the outcome at a follow-up of 61 months (range, 24-85 months) was determined. RESULTS: Compared with the healthy control group, the study group had significantly higher levels of TIMP1, PIIINP, CITP, PINP and NT-pro-BNP (p<0.05, each). The levels of PIIINP and CITP were significantly higher among patients with an SRV mass index above the mean value. The level of PIIINP was significantly higher among patients with an SRV EDV index above the mean value. CITP was significantly elevated in SRV late gadolinium enhanced (LGE) positive patients, compared to patients without SRV LGE. MMP9 and TIMP1 predicted an adverse clinical outcome on univariate Cox proportional hazard survival analysis in addition to well proven predictors of outcome (SRV EF and NYHA). CONCLUSIONS: We demonstrated a pattern of altered collagen turnover adversely related with the indices of SRV remodeling and an adverse clinical outcome in patients with SRV.