Assessment of Diastolic Function in Single-Ventricle Patients After the Fontan Procedure.
Ontology highlight
ABSTRACT: Patients with functional single ventricles after the Fontan procedure have abnormal cardiac mechanics. The aims of this study were to determine factors that influence diastolic function and to describe associations of diastolic function with current clinical status.Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study. Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseudonymization (grade 2), or restrictive (grade 3). Studies were also classified dichotomously (restrictive pattern present or absent). Relationships between DFG and pre-Fontan variables (e.g., ventricular morphology, age at Fontan, history of volume-unloading surgery) and current status (e.g., systolic function, valvar regurgitation, exercise performance) were explored.DFG was calculable in 326 of 546 subjects (60%) (mean age, 11.7 ± 3.3 years). Overall, 32% of patients had grade 0, 9% grade 1, 37% grade 2, and 22% grade 3 diastolic function. Although there was no association between ventricular morphology and DFG, there was an association between ventricular morphology and E', which was lowest in those with right ventricular morphology (P < .001); this association remained significant when using Z scores adjusted for age (P < .001). DFG was associated with achieving maximal effort on exercise testing (P = .004); the majority (64%) of those not achieving maximal effort had DFG 2 or 3. No additional significant associations of DFG with laboratory or clinical measures were identified.Assessment of diastolic function by current algorithms results in a high percentage of patients with abnormal DFG, but few clinically or statistically significant associations were found. This may imply a lack of impact of abnormal diastolic function on clinical outcomes in this cohort, or it may indicate that the methodology may not be applicable to pediatric patients with functional single ventricles.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 20160910 11
<h4>Background</h4>Patients with functional single ventricles after the Fontan procedure have abnormal cardiac mechanics. The aims of this study were to determine factors that influence diastolic function and to describe associations of diastolic function with current clinical status.<h4>Methods</h4>Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study. Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseu ...[more]
Project description:BackgroundMulticenter longitudinal objective data for survival into adulthood of patients who have undergone Fontan procedures are lacking.ObjectivesThis study sought to describe transplant-free survival and explore relationships between laboratory measures of ventricular performance and functional status over time.MethodsExercise testing, echocardiography, B-type natriuretic peptide, functional health assessment, and medical history abstraction were repeated 9.4 ± 0.4 years after the Fontan Cross-Sectional Study (Fontan 1) and compared with previous values. Cox regression analysis explored risk factors for interim death or cardiac transplantation.ResultsFrom the original cohort of 546 subjects, 466 were contacted again, and 373 (80%) were enrolled at 21.2 ± 3.5 years of age. Among subjects with paired testing, the percent predicted maximum oxygen uptake decreased (69 ± 14% vs. 61 ± 16%; p < 0.001; n = 95), ejection fraction decreased (58 ± 11% vs. 55 ± 10%; p < 0.001; n = 259), and B-type natriuretic peptide increased (median [interquartile range] 13 [7 to 25] pg/mol vs. 18 [9 to 36] pg/mol; p < 0.001; n = 340). At latest follow-up, a lower Pediatric Quality of Life Inventory physical summary score was associated with poorer exercise performance (R2 adjusted = 0.20; p < 0.001; n = 274). Cumulative complications since the Fontan procedure included additional cardiac surgery (32%), catheter intervention (62%), arrhythmia treatment (32%), thrombosis (12%), and protein-losing enteropathy (8%). Since Fontan 1, 54 subjects (10%) have received a heart transplant (n = 23) or died without transplantation (n = 31). The interval risk of death or/cardiac transplantation was associated with poorer ventricular performance and functional health status assessed at Fontan 1, but it was not associated with ventricular morphology, the subject's age, or the type of Fontan connection.ConclusionsInterim transplant-free survival over 12 years in this Fontan cohort was 90% and was independent of ventricular morphology. Exercise performance decreased and was associated with worse functional health status. Future interventions might focus on preserving exercise capacity. (Relationship Between Functional Health Status and Ventricular Performance After Fontan-Pediatric Heart Network; NCT00132782).
Project description:BackgroundIn children with single right ventricular (RV) anomalies, changes in RV size and function may be influenced by shunt type chosen at the time of the Norwood procedure.ObjectivesThe study sought to identify shunt-related differences in echocardiographic findings at 14 months and ≤6 months pre-Fontan in survivors of the Norwood procedure.MethodsWe compared 2-dimensional and Doppler echocardiographic indices of RV size and function, neo-aortic and tricuspid valve annulus dimensions and function, and aortic size and patency at 14.1 ± 1.2 months and 33.6 ± 9.6 months in subjects randomized to a Norwood procedure using either the modified Blalock-Taussig shunt (MBTS) or right ventricle to pulmonary artery shunt (RVPAS).ResultsAcceptable echocardiograms were available at both time points in 240 subjects (114 MBTS, 126 RVPAS). At 14 months, all indices were similar between shunt groups. From the 14-month to pre-Fontan echocardiogram, the MBTS group had stable indexed RV volumes and ejection fraction, while the RVPAS group had increased RV end-systolic volume (p = 0.004) and decreased right ventricular ejection fraction (RVEF) (p = 0.004). From 14 months to pre-Fontan, the treatment groups were similar with respect to decline in indexed neo-aortic valve area, >mild neo-aortic valve regurgitation (<5% at each time), indexed tricuspid valve area, and ≥moderate tricuspid valve regurgitation (<20% at each time).ConclusionsInitial Norwood shunt type influences pre-Fontan RV remodeling during the second and third years of life in survivors with single RV anomalies, with greater RVEF deterioration after RVPAS. Encouragingly, other indices of RV function remain stable before Fontan regardless of shunt type. (Comparison of Two Types of Shunts in Infants with Single Ventricle Defect Undergoing Staged Reconstruction-Pediatric Heart Network; NCT00115934).
Project description:To assess self-reported quality of life (QOL) in a large multicenter cohort of adolescent and young adults surviving Fontan.Cross-sectional. The Pediatric Quality of Life Inventory (PedsQL) was administered to 408 survivors of Fontan ages 13-25 years enrolled in the Pediatric Heart Network Fontan Follow-up Study. Subjects also completed either the Child Health Questionnaire (age <19 years) or Short Form Health Survey (age ? 19 years). PedsQL data were compared with matched controls without a chronic health condition. Correlations between the measures were examined.Mean PedsQL scores for subjects receiving Fontan were significantly lower than those for the control group for physical and psychosocial QOL (P < .001). Overall, 45% of subjects receiving Fontan had scores in the clinically significant impaired range for physical QOL with 30% in the impaired range for psychosocial QOL. For each 1 year increase in age, the physical functioning score decreased by an average of 0.76 points (P = .004) and the emotional functioning score decreased by an average of 0.64 points (P = .03). Among subjects ?19 years of age, the physical functioning score decreased by an average of 2 points for each year increase in age (P = .02). PedsQL scale scores were significantly correlated with conceptually related Child Health Questionnaire (P < .001) and Short Form Health Survey scores (P < .001).Survivors of Fontan are at risk for significantly impaired QOL which may decline with advancing age. Routine assessment of QOL is essential to inform interventions to improve health outcomes. The PedsQL allowed QOL assessment from pediatrics to young adulthood.ClinicalTrials.gov: NCT00132782.
Project description:Background Heart failure phenotyping in single-ventricle Fontan patients is challenging, particularly in patients with normal ejection fraction (EF). The objective of this study was to identify Fontan patients with abnormal diastolic function, who are high risk for heart failure with preserved ejection fraction (HFpEF), and characterize their cardiac mechanics, exercise function, and functional health status. Methods and Results Data were obtained from the Pediatric Heart Network Fontan Cross-sectional Study database. EF was considered abnormal if <50%. Diastolic function was defined as abnormal if the diastolic pressure:volume quotient (lateral E:e'/end-diastolic volume) was >90th percentile (≥0.26 mL-1). Patients were divided into: controls=normal EF and diastolic function; systolic dysfunction (SD) = abnormal EF with normal diastolic function; diastolic dysfunction (DD) = normal EF with abnormal diastolic pressure:volume quotient. Exercise function was quantified as percent predicted peak VO2. Physical Functioning Summary Score (FSS) was reported from the Child Health Questionnaire. A total of 239 patients were included, 177 (74%) control, 36 (15%) SD, and 26 (11%) DD. Median age was 12.2 (5.4) years. Arterial elastance, a measure of arterial stiffness, was higher in DD (3.6±1.1 mm Hg/mL) compared with controls (2.5±0.8 mm Hg/mL), P<0.01. DD patients had lower predicted peak VO2 compared with controls (52% [20] versus 67% [23], P<0.01). Physical FSS was lower in DD (45±13) and SD (44±13) compared with controls (50±7), P<0.01. Conclusions Fontan patients with abnormal diastolic function and normal EF have decreased exercise tolerance, decreased functional health status, and elevated arterial stiffness. Identification of patients at high risk for HFpEF is feasible and should be considered when evaluating Fontan patients.
Project description:Galectin-3 may play a role in cardiac and noncardiac fibrosis, and elevated circulating levels of this protein predict adverse outcomes in patients with heart failure who do not have congenital heart disease. We investigated galectin-3 in adults with single-ventricle Fontan circulation, patients who are prone to premature clinical deterioration in the context of extensive multiorgan fibrosis.We measured plasma galectin-3 concentrations in 70 ambulatory adult Fontan patients and 21 age- and sex-matched control participants. Galectin-3 level was significantly higher in the Fontan group (11.85 ng/mL, interquartile range 9.9 to 15.0 ng/mL) versus the control group (9.4 ng/mL, interquartile range 8.2 to 10.8 ng/mL; P<0.001). Among Fontan patients, galectin-3 was positively correlated with age, uric acid, and high-sensitivity C-reactive protein and negatively correlated with estimated glomerular filtration rate. There was no significant relationship between galectin-3 and oxygen saturation, Fontan type, or ventricular morphology. Over a median follow-up of 461 days, 15 events occurred among the Fontan patients: 12 nonelective hospitalizations (with 2 subsequent deaths) and 3 deaths without prior hospitalization. Patients with elevated galectin-3 (n=19, defined as >2 SD above the control group mean value) had a higher risk of nonelective hospitalization or death (hazard ratio 6.0, 95% CI 2.1 to 16.8, P<0.001). This relationship persisted after individual adjustment for covariates including age, New York Heart Association functional class, C-reactive protein, and estimated glomerular filtration rate and after multivariable adjustment for independently predictive covariates (hazard ratio 9.2, 95% CI 2.4 to 35.2, P=0.001).Galectin-3 concentrations are elevated among adults with a Fontan circulation, and elevated galectin-3 is associated with an increased risk of nonelective cardiovascular hospitalization or death.
Project description:ObjectivesTo define whether adults with a Fontan circulation, who have lifelong venous congestion and limited cardiac output, have impaired glomerular filtration rate (GFR) or elevated urinary biomarkers of kidney injury.MethodsWe measured circulating cystatin C and creatinine (n=70) and urinary creatinine, albumin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl glucosaminidase (NAG) (n=59) in ambulatory adult Fontan patients and 20 age-matched and sex-matched controls. Urinary biomarkers were normalised to urine creatinine concentration. Survival free from non-elective cardiovascular hospitalisation was compared by estimated GFR and urinary biomarker levels using survival analysis.ResultsCystatin C GFR was lower in the Fontan group compared with controls (114.2±22.8 vs 136.3±12.8 mL/min/1.73 m2, p<0.0001); GFR<90 mL/min/1.73 m2 in 14.3% vs 0% of controls. Albumin-to-creatinine ratio (ACR), KIM-1 and NAG were elevated compared with controls; ACR=23.2 (7.6-38.3) vs 3.6 (2.5-5.7) mg/g, p<0.0001; NAG=1.8 (1.1-2.6) vs 1.1 (0.9-1.6) U/g, p=0.02; KIM-1=0.91 (0.52-1.45) vs 0.33 (0.24-0.74) ng/mg, p=0.001. Microalbuminuria, ACR>30 mg/g, was present in 33.9% of the Fontan patients but in none of the controls. Over median 707 (IQR 371-942)-day follow-up, 31.4% of patients had a clinical event. Higher KIM-1 and NAG were associated with higher risk of non-elective hospitalisation or death (HR/+1 SD=2.1, 95% CI 1.3 to 3.3, p=0.002; HR/+1 SD=1.6, 95% CI 1.05 to 2.4, p=0.03, respectively); cystatin C GFR was associated with risk of the outcome (HR/+1 SD=0.66, 95% CI 0.48 to 0.90, p=0.009) but creatinine-based GFR was not (HR/+1 SD=0.91, 95% CI 0.61 to 1.38, p=0.66). Neither ACR nor NGAL was associated with events.ConclusionsThe Fontan circulation is commonly associated with reduced estimated GFR and evidence for glomerular and tubular injury. Those with lower cystatin C GFR and tubular injury are at increased risk of adverse outcomes.
Project description:In the Single Ventricle Reconstruction trial, infants with hypoplastic left heart syndrome (HLHS) who received a right-ventricle-to-pulmonary-artery shunt (RVPAS) versus a modified Blalock-Taussig shunt (MBTS) had lower early postoperative mortality, but more complications at 14 months. We explored the effect of shunt type and other patient, medical, and surgical factors on postoperative length of stay (LOS) after the Fontan operation.Fontan postoperative course was ascertained from medical record review. Cox proportional hazards modeling was used to identify factors associated with LOS.Of 327 subjects who underwent Fontan, 323 were analyzed (1 death, 1 biventricular repair, 2 with missing data). Median age and weight at Fontan were 2.8 years (interquartile range [IQR]: 2.3, 3.4) and 12.7 kg (IQR: 11.4, 14.1), respectively. Fontan type was extracardiac in 55% and lateral tunnel in 45%; 87% were fenestrated. The RVPAS and MBTS subjects had similar LOS (median 11 days [IQR: 9, 18] vs 10 days [IQR: 9, 13]; P = .23). Independent risk factors for longer LOS were treatment center (P < .01), LOS at stage II (hazard ratio [HR] 1.02 for each additional day; P < .01), and pre-Fontan complications (HR 1.03 for each additional complication; P = .04). Use of deep hypothermic circulatory arrest at Fontan (HR 0.64; P = .02) was independently associated with shorter LOS. When center was excluded from the model, pre-Fontan complications and use of circulatory arrest were no longer significant; instead, older age at stage II (HR 1.08 for each additional month; P = .01) predicted longer LOS. In 254 subjects who had a pre-Fontan echocardiogram, at least moderate tricuspid regurgitation was independently associated with longer LOS, both with center (HR 1.72; P < .01) and without center in the model (HR 1.49; P = .02).In this multicenter prospective cohort of subjects with HLHS, Norwood shunt type was not associated with Fontan LOS. Rather, global measures of earlier medical complexity indicate greater likelihood of longer LOS after the Fontan operation.
Project description:BackgroundWhile echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.MethodsData from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman's test.ResultsMedian age at echocardiogram was 4.6 (range 2.5-7.4) months. Median ventricular end-diastolic pressure was 7 (range 3-19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range -35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = -0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure.ConclusionIn this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.
Project description:Data on resting energy expenditure (REE) and oxygen consumption (VO(2)) after pediatric cardiopulmonary bypass (CPB) will facilitate optimal nutrient prescription.The authors measured continuous REE and VO(2), using an in-line indirect calorimetery (IC) in 30 consecutive children with single-ventricle physiology immediately after Fontan surgery. REE during steady state at 8 hours after surgery was compared with standard equation-estimated energy expenditure (EEE). Patients were classified into 3 groups: hypermetabolic (measured REE [MREE]/EEE ratio >1.2), hypometabolic (MREE/EEE ratio <0.8), and normometabolic (MREE/EEE ratio 0.8-1.2). Demographic, anthropometric, and perioperative clinical characteristics were examined for their correlation with metabolic status.In 26 of 30 patients with completed IC, mean REE at 8 hours after surgery was 57 ± 20 kcal/kg/d, and mean VO(2) was 110 ± 35 mL/min. Mean values of VO(2) and REE did not change within the first 24 hours after surgery. There was poor correlation between MREE at 8 hours and the EEE using the World Health Organization equation (r = 0.32, P = .11). Most patients (n = 19, 73%) were either normometabolic or hypometabolic. Lack of hypermetabolism was significantly associated with higher intraoperative serum lactate level and positive fluid balance compared with the rest of the group.The authors report a low prevalence of hypermetabolism in children with single-ventricle defects after Fontan surgery. Measured REE had poor correlation with equation-estimated energy expenditure in a majority of the cohort. The absence of increased energy expenditure after CPB will influence energy prescription in this group.
