Analysis of Inflammatory Cytokines in Postoperative Fontan Pleural Drainage.

Prolonged pleural drainage is a common complication in patients after Fontan palliation and is associated with short- and long- term morbidities. Among many potential etiologies, prolonged drainage has an inflammatory component, but there are no descriptions of cytokines in Fontan pleural drainage to date. This study aimed to examine the inflammatory make-up of Fontan pleural drainage. This prospective age-range-matched cohort study recruited 25 patients undergoing Fontan procedure and 15 bi-ventricular patients undergoing cardiopulmonary bypass (CPB). Chest tube samples were taken on postoperative day (POD) 1-4, 7, and 10. Cytokines were measured using Bio-Plex Assays. Univariate comparisons were made in patient characteristics and cytokine levels. Median age was 3.7 y (IQR 2.8-3.9) for controls and 2.5 y (IQR 2.1-2.9) in Fontan patients (p = 0.02). Median drainage duration and daily volume was higher in Fontan patients (both p < 0.001). Inflammatory cytokines (IL-17A, IFN-y, MIP-1ß, and TNF-α) were higher in Fontan patients than controls (all p < 0.02). There was an increase in pro-inflammatory cytokines (IL-8, MIP-1ß, and TNF-α) from POD1 to the last chest tube day (LCD) in Fontan patients (all p < 0.0001) and a decrease in the anti-inflammatory cytokine IL-10 (p = 0.001). There was no difference in cytokine concentration from POD1 to LCD among controls. There was a significant association with the cytokine concentration of TNF-α on POD1 and duration of chest tube drainage (p < 0.05). Inflammatory cytokine levels in the pleural fluid of Fontan patients are higher compared to bi-ventricular controls and rise over time where controls do not. This suggests ongoing localized inflammation that is not a result of CPB alone and may be an important contributor to pleural drainage in patients after the Fontan procedure.

Relation of Increased Epicardial Fat After Fontan Palliation to Cardiac Output and Systemic Ventricular Ejection Fraction.

Epicardial fat produces multiple proinflammatory cytokines and is associated with adverse cardiovascular events. Inflammation and resultant endothelial dysfunction may play a role in progressive myocardial dysfunction among adults with single ventricle physiology after Fontan palliation, but the potential impact of increased epicardial fat volume (EFV) has not been studied. This study sought to determine if there is greater EFV in Fontan patients compared with a group of repaired tetralogy of Fallot (rTOF) patients. We retrospectively measured EFV manually on cardiac magnetic resonance imaging in Fontan patients, ≥15 years, and 1:1 age, sex, and body mass index-matched patients with rTOF. EFV was indexed to body surface area. A random subset of studies was re-measured to assess intra- and interobserver reliability. Fontan patients (n = 63, median age 21.6 years, 51% male, mean body mass index 24.2 ± 5.6 kg/m2) had a larger indexed EFV compared with matched rTOF patients (75.3 ± 29.2 ml/m2 vs 60.0 ± 19.9 ml/m2, p = 0.001). In Fontan patients, indexed EFV was inversely correlated with ventricular ejection fraction (r = -0.26, p = 0.04) and cardiac index (r = -0.33, p = 0.01). Intra- and interobserver reliabilities of the indexed EFV measurements in both groups were excellent (intraclass correlation coefficient ranges from 0.93 to 0.97). In conclusion, indexed EFV is higher in Fontan patients compared with patients with rTOF and is associated with lower ventricular ejection fraction and cardiac index. Increased EFV could play a role in the failing Fontan circulation, but longitudinal studies are necessary to establish any causative role.

Long-Term Outcomes After Surgical Pulmonary Arterioplasty and Risk Factors for Reintervention.

BACKGROUND: Although surgical patch arterioplasty is the conventional therapy for branch pulmonary artery (PA) stenosis, limited data exist on long-term outcomes. We examined the incidence of and risk factors for reintervention after surgical arterioplasty for branch PA stenosis in biventricular congenital heart disease. METHODS: This retrospective cohort study included patients with 2-ventricle physiology who underwent patch arterioplasty for PA stenosis at a single high-volume congenital heart center during a 10-year period. Freedom from surgical or percutaneous reintervention for recurrent PA stenosis was evaluated. Univariate and multivariable Cox regression analyses were performed to determine risk factors for reintervention. RESULTS: Among 135 patients, the median age at patch arterioplasty was 0.9 years. Survival to hospital discharge (or 30 days postoperatively) was 96%. During a median follow-up period of 4.0 years, reintervention for PA stenosis occurred in 38 of 115 patients (33%) at a median time to reintervention of 1.4 years. The overall 10-year reintervention rate was 54%. In univariate analysis, age less than 30 days at initial arterioplasty, congenital PA stenosis (vs acquired), and bilateral PA stenosis (vs unilateral) were significantly associated with reintervention. In multivariable analysis, neonatal age (adjusted hazard ratio, 3.6; p = 0.002) and bilateral PA stenosis (adjusted hazard ratio, 2.8; p = 0.005) remained independently associated with reintervention. CONCLUSIONS: Long-term reintervention for recurrent PA stenosis after patch arterioplasty is common. Patients with bilateral PA stenosis or age younger than 30 days at the time of the index pulmonary arterioplasty are at higher risk for reintervention. These patients may benefit from frequent monitoring or novel approaches to repair.

Temporal relationship between instantaneous pressure gradients and peak-to-peak systolic ejection gradient in congenital aortic stenosis.

OBJECTIVE: We sought to identify a time during cardiac ejection when the instantaneous pressure gradient (IPG) correlated best, and near unity, with peak-to-peak systolic ejection gradient (PPSG) in patients with congenital aortic stenosis. Noninvasive echocardiographic measurement of IPG has limited correlation with cardiac catheterization measured PPSG across the spectrum of disease severity of congenital aortic stenosis. A major contributor is the observation that these measures are inherently different with a variable relationship dependent on the degree of stenosis. DESIGN: Hemodynamic data from cardiac catheterizations utilizing simultaneous pressure measurements from the left ventricle (LV) and ascending aorta (AAo) in patients with congenital valvar aortic stenosis was retrospectively reviewed over the past 5 years. The cardiac cycle was standardized for all patients using the percentage of total LV ejection time (ET). Instantaneous gradient at 5% intervals of ET were compared to PPSG using linear regression and Bland-Altman analysis. RESULTS: A total of 22 patients underwent catheterization at a median age of 13.7 years (interquartile range [IQR] 10.3-18.0) and median weight of 51.1 kg (IQR 34.2-71.6). The PPSG was 46.5 ± 12.6 mm Hg (mean ± SD) and correlated suboptimally with the maximum and mean IPG. The midsystolic IPG (occurring at 50% of ET) had the strongest correlation with the PPSG ( PPSG = 0.97(IPG50%)-1.12, R2 = 0.88), while the IPG at 55% of ET was closest to unity ( PPSG = 0.997(IPG55%)-1.17, R2 = 0.87). CONCLUSIONS: The commonly measured maximum and mean IPG are suboptimal estimates of the PPSG in congenital aortic stenosis. Using catheter-based data, IPG at 50%-55% of ejection correlates well with PPSG. This may allow for a more accurate estimation of PPSG via noninvasive assessment of IPG.

Twenty years of experience with intraoperative pulmonary artery stenting.

OBJECTIVES: To describe our 20-year experience with intraoperative pulmonary artery (PA) stent placement and evaluate long-term patient outcomes, specifically the need and risk factors for reintervention. BACKGROUND: Intraoperative PA stent placement is an alternative to surgical patch arterioplasty and percutaneous angioplasty or stent placement to treat branch PA stenosis. METHODS: We performed a retrospective review of all intraoperative PA stents placed at our institution from 1994-2013. Patient and stent characteristics and outcome data were collected. Risk factors associated with reintervention were identified using univariate cox regression analysis. RESULTS: Eighty-one PA stents were placed in 68 patients. The procedural complication rate was 4.4%. During a median follow-up period of 6 years (interquartile range [IQR] 0.9-12.7), 30 patients (44%) underwent reintervention on the stented PA with a median time to first reintervention of 2.6 years (IQR 0.7-4.4 years). The first reintervention was surgical in 30% and catheter-based in 70%. Risk factors for reintervention included age < 18 months (Hazard ratio [HR] 2.97, P = 0.005) and body surface area < 0.47 m2 (HR 3.20, P = 0.003) at the time of stent implantation, and the presence of multiple aortopulmonary collaterals in patients with tetralogy of Fallot (HR 4.61, P = 0.003). CONCLUSIONS: Intraoperative PA stent implantation is a safe and effective alternative to percutaneous stent implantation and offers several advantages, including the ability to implant adult-size stents in small patients while avoiding injury to peripheral vessels, to position stents to facilitate future percutaneous stent redilation, and to access the PAs directly, which eliminates radiation exposure. © 2017 Wiley Periodicals, Inc.

Left ventricular function by pressure-volume loop analysis before and after percutaneous repair of large atrial septal defects.

AIM: The intent of the present study was to evaluate changes in ventricular function with percutaneous closure of atrial septal defect (ASD), as it is associated with alterations in ventricular loading and function. Transcatheter occlusion of ASD imparts acute changes in volume loading of the left ventricle (LV) that obscures measurement of ventricular function by load-dependent indices. To differentiate between changes in ventricular loading and function, load-independent indices of ventricular function must be utilized. METHODS: During transcatheter occlusion of ASD, subjects underwent measurement of LV pressure and volume by the conductance catheter method. Load-dependent indices of ventricular function included: systolic and diastolic pressures, +dP/dtmax , and -dP/dtmax . Load-independent indices included: elastance and tau, the preload-independent time constant ofisovolumic relaxation. To obtain elastance, afterload was augmented by phenylephrine bolus pre- and post-device occlusion. RESULTS: In total, 29 patients (age 2-79 years) underwent ASD device occlusion (device size 12-38 mm, median 28 mm). Load-dependent indices were obtained in all, and satisfactory pressure-volume loops in 11. At baseline, LV end-diastolic pressure was 5-23 mmHg (13 ± 5 mmHg) and tau was 31 ± 6 ms. Postclosure of the ASD, LV systolic and diastolic pressures rose by 10 ± 11 mmHg and 5 ± 3 mmHg, respectively (P < 0.05), and +dP/dtmax rose from 1,288 ± 313 mmHg/sec to 1,415 ± 465 mmHg/sec (P < 0.05), but -dP/dtmax was unchanged. Elastance significantly improved (9.4 ± 8.3 mmHg/mL vs. 13.0 ± 7.3 mmHg/mL, P < 0.05) and tau was unchanged. CONCLUSIONS: Transcatheter occlusion of ASD is associated with acute improvement in load-independent indices of systolic function in this cohort, without significant worsening of the preload-independent index of diastolic function.

Impact of vitamin C on endothelial function and exercise capacity in patients with a Fontan circulation.

OBJECTIVE: To evaluate the impact of antioxidant therapy on functional health status in Fontan-palliated patients. Design. Prospective, randomized, double-blind, placebo-controlled trial. PATIENTS: Fifty-three generally asymptomatic Fontan patients. INTERVENTIONS: Patients were randomized to receive either high-dose ascorbic acid (vitamin C) or placebo for 4 weeks. OUTCOME MEASURES: Peripheral vascular function, as measured with endothelium-dependent digital pulse amplitude testing (EndoPAT), and exercise capacity were assessed before and after study drug treatment. Primary outcome measures included the EndoPAT index and peripheral arterial tonometry (PAT) ratio, both validated markers of vascular function. Secondary outcome measures included peak oxygen consumption and work. RESULTS: Twenty-three vitamin C- and 21 placebo-assigned subjects completed the protocol (83%). Median age and time from Fontan completion were 15 (interquartile range [IQR] 11.7-18.2) and 11.9 years (IQR 9.0-15.7), respectively. Right ventricular morphology was dominant in 30 (57%). Outcome measures were similar between groups at baseline. Among all subjects, vitamin C therapy was not associated with a statistical improvement in either primary or secondary outcome measures. In subjects with abnormal vascular function at baseline, compared with placebo, vitamin C therapy more frequently resulted in normalization of the EndoPAT index (45% vs. 17%) and PAT ratio (38% vs. 13%). CONCLUSIONS: Short-term therapy with vitamin C does not alter endothelial function or exercise capacity in an asymptomatic Fontan population overall. Vitamin C may provide benefit to a subset of Fontan patients with abnormal vascular function.

Use of a pressure guidewire in fetal cardiac intervention for critical aortic stenosis.

Fetal cardiac intervention for critical aortic stenosis (AS) with evolving hypoplastic left heart syndrome is performed in an attempt to maintain a biventricular circulation postnatally. The procedure has been hindered by technical challenges and poor candidate selection. We report here the novel use of a pressure guidewire during aortic valvuloplasty in a fetus at 21 weeks' gestation with critical AS and evolving hypoplastic left heart syndrome. Use of a pressure guidewire during fetal cardiac intervention offers several potential advantages over existing protocols. This technique augments fetal ultrasound as it relates to operator awareness of catheter and wire position (with continuous monitoring of pressure waveforms), improves on intraprocedural fetal hemodynamic monitoring and responsiveness to resuscitation, and provides a rich new data set of invasive fetal hemodynamics. This data set offers tremendous potential with regards to improving candidate selection and postintervention prognostication. In addition, we provide the first, to our knowledge, characterization of intracardiac pressures in a human fetus with congenital heart disease. Given the realized and potential benefits associated with this technique, use of a pressure guidewire may become standard of care for all fetal cardiac interventions.

Usefulness of peripheral vascular function to predict functional health status in patients with Fontan circulation.

After the Fontan operation, patients are at a substantial risk of the development of impaired functional health status. Few early markers of suboptimal outcomes have been identified. We sought to assess the association between peripheral vascular function and functional health status in Fontan-palliated patients. Asymptomatic Fontan patients (n = 51) and age- and gender-matched healthy controls (n = 22) underwent endothelial pulse amplitude testing using a noninvasive fingertip peripheral arterial tonometry (PAT) device. Raw data were transformed into the PAT ratio, an established marker of vascular function. Cardiopulmonary exercise testing was performed using the Bruce protocol. In the Fontan cohort, 94% of patients were New York Heart Association functional class I and 88% had a B-type natriuretic peptide level of <50 pg/ml. The baseline pulse amplitude, a measure that reflects the arterial tone at rest, was greater in the Fontan patients than in the controls (median 2.74, interquartile range 1.96 to 4.13 vs median 1.86, interquartile range 1.14 to 2.79, p = 0.03). The PAT ratio, a measure of reactive hyperemia, was lower in Fontan patients (median 0.17, interquartile range -0.04 to 0.44, vs median 0.50, interquartile range 0.27 to 0.74, p = 0.002). The key parameters of exercise performance, including peak oxygen consumption (median 28.8 ml/kg/min, interquartile range 25.6 to 33.2 vs median 45.5 ml/kg/min, interquartile range 41.7 to 49.9, p <0.0001) and peak work (median 192 W, interquartile range 150 to 246 vs median 330, interquartile range 209 to 402 W, p <0.0001), were lower in Fontan patients than in the controls. The PAT ratio correlated with the peak oxygen consumption (r = 0.28, p = 0.02) and peak work (r = 0.26, p = 0.03). In conclusion, in an asymptomatic Fontan population, there is evidence of reduced basal peripheral arterial tone and vasodilator response, suggesting dysfunction of the endothelium-derived nitric oxide pathway. Vasodilator function appears to correlate with exercise performance.

Relation of systemic venous return, pulmonary vascular resistance, and diastolic dysfunction to exercise capacity in patients with single ventricle receiving fontan palliation.

Fontan patients have a reduced exercise capacity, primarily owing to limitations in the ability to augment pulmonary blood flow and stroke volume. To date, the mechanism of peak exercise pulmonary blood flow restriction has not been elucidated. We performed a single-center, prospective, crossover trial of supine and upright exercise in Fontan patients and healthy controls to determine the mechanisms of exercise limitation in the Fontan-palliated patient. A total of 29 Fontan patients and 16 control subjects completed the protocol. The duration of exercise, percentage of predicted peak oxygen consumption (VO(2)) and peak work were reduced in the Fontan group, regardless of posture (p < or = 0.03). The percentage of predicted oxygen pulse, a surrogate for pulmonary stroke volume, was not increased with supine posture in the Fontan cohort (upright, 82.3 + or - 18.8% vs supine, 82.4 + or - 19.7%; p = 0.6). In both groups, the percentage of predicted peak VO(2) was lower with supine exercise than with upright exercise (p < or =0.002). Diastolic dysfunction was present in 57% of the Fontan patients and was associated with a reduced percentage of predicted peak VO(2) (p = 0.04) and supine peak work (p = 0.008). Six Fontan patients who underwent supine exercise with indwelling catheters failed to demonstrate the expected decrease in pulmonary vascular resistance characteristically seen with peak exercise (at rest, 2.8 + or - 0.7 mm Hg/L/min/m(2) vs at peak, 2.8 + or - 0.9 mm Hg/L/min/m(2); p = 0.9). In conclusion, supine exercise in Fontan patients does not result in an increased VO(2) or oxygen pulse, suggesting that inadequate venous return might not be the primary limitation of exercise capacity in this population. Diastolic dysfunction and relatively excessive peak exercise pulmonary vascular resistance might be more important factors in Fontan exercise limitation.

Long-term follow up of secundum atrial septal defect closure with the amplatzer septal occluder.

BACKGROUND: During the past 15 years, closure of a secundum atrial septal defect (ASD) has moved from a surgical to a percutaneous transcatheter approach. Few long-term studies of the efficacy and safety of closure of an ASD by an Amplatzer septal occluder (ASO) exist. METHODS: To examine the long-term results of secundum ASD closure using the ASO, data on 94 patients who underwent secundum ASD closure with the ASO between 1998 and 2002 were available and reviewed. Data regarding residual shunt, chest pain, palpitations, arrhythmias, headaches, transient ischemic attacks, cerebrovascular accidents, and mortality were collected. RESULTS: Seven (7.4%) subjects had residual shunts immediately following ASO placement. During follow-up, 4 residual shunts closed for a complete closure rate of 97%. Eighteen (19%) patients reported chest pain during the follow-up period. Twenty-three patients (24%) reported palpitations during the follow up period, 7 were documented arrhythmias, including supraventricular tachycardia, atrial fibrillation, and premature ventricular beats. Migraine headaches were new-onset in 4 patients. Migraine cessation occurred in 2 patients after secundum ASD closure. One child died from a cerebral vascular event 18 months following device placement. Only 1 patient developed mild aortic insufficiency. CONCLUSION: These data indicate that for up to 120 months of patient follow-up, the ASO continues to be a safe device. Residual shunts and arrhythmias have low incidence post-ASO placement. Given the mortality in one high-risk patient, further investigation into anti-platelet therapy after device placement is warranted.

Serial changes in norepinephrine kinetics associated with feeding dogs a high-fat diet.

The role of increased sympathetic nervous system (SNS) activity in the pathogenesis of obesity hypertension and insulin resistance is controversial. Eight dogs were instrumented and fed a high-fat diet (HFD) for 6 weeks. Dogs were evaluated for changes in weight, blood pressure, insulin resistance, and norepinephrine (NE) kinetics using a two-compartment model. The HFD resulted in weight gain, hypertension, and insulin resistance. During the 6 weeks of the HFD, although plasma NE concentration trended toward increasing (P=.09), SNS, assessed by NE kinetic studies, significantly increased (P=.009). Within 1 week of starting the HFD, NE release into the extravascular compartment (NE(2)) increased from 3.44+/-0.59 microg/mL to 4.87+/-0.80 microg/mL (P<.01) and this increase was maintained over the next 5 weeks of the HFD (NE(2) at week 6 was 4.66+/-0.97 microg/mL). In addition to the increased NE(2) there was also a significant increase in NE clearance (P=.04). There were significant correlations between the increase in NE(2) and both the development of insulin resistance and hypertension. This study supports the hypothesis that activation of the SNS plays a pivotal role in the metabolic and hemodynamic changes that occur with weight gain induced by HFD.

Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing.

Despite compliance with lifestyle recommendations, some children and adolescents with high-risk hyperlipidemia will require lipid-lowering drug therapy, particularly those with familial hypercholesterolemia. The purpose of this statement is to examine new evidence on the association of lipid abnormalities with early atherosclerosis, discuss challenges with previous guidelines, and highlight results of clinical trials with statin therapy in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. Recommendations are provided to guide decision-making with regard to patient selection, initiation, monitoring, and maintenance of drug therapy.

Superior vena cava thrombectomy with the X-SIZER catheter system in a child with Fontan palliation.

A 4-year-old female with hypoplastic left heart syndrome and Fontan palliation presented with severe neurologic impairment from thrombosis of the superior vena cava (SVC). She underwent successful SVC thrombectomy with the X-SIZER Thrombectomy Catheter System, followed by balloon angioplasty. She demonstrated rapid improvement in her neurologic deficits after the procedure. This represents the first published use of the X-SIZER in a child and its first published use for SVC thrombectomy.