Cardiac magnetic resonance assessment of acute rejection and cardiac allograft vasculopathy in pediatric heart transplant.

BACKGROUND: In pediatric heart transplant (PHT), cardiac catheterization with endomyocardial biopsy (EMB) is standard for diagnosing acute rejection (AR) and cardiac allograft vasculopathy (CAV) but is costly and invasive. OBJECTIVES: To evaluate the ability of cardiac magnetic resonance (CMR) to noninvasively identify differences in PHT patients with AR and CAV. METHODS: Patients were enrolled at three children's hospitals. Data were collected from surveillance EMB or EMB for-cause AR. Patients were excluded if they had concurrent diagnoses of AR and CAV, CMR obtained >7days from AR diagnosis, they had EMB negative AR, or could not undergo contrasted, unsedated CMR. Kruskal-Wallis test was used to compare groups: (1) No AR or CAV (Healthy), (2) AR, (3) CAV. Wilcoxon rank-sum test was used for pairwise comparisons. RESULTS: Fifty-nine patients met inclusion criteria (median age 17years [IQR 15-19]) 10 (17%) with AR, and 11 (19%) with CAV. AR subjects had worse left ventricular ejection fraction compared to Healthy patients (p = 0.001). Global circumferential strain (GCS) was worse in AR (p = 0.054) and CAV (p = 0.019), compared to Healthy patients. ECV, native T1, and T2 z-scores were elevated in patients with AR. CONCLUSIONS: CMR was able to identify differences between CAV and AR. CAV subjects had normal global function but abnormal GCS which may suggest subclinical dysfunction. AR patients have abnormal function and tissue characteristics consistent with edema (elevated ECV, native T1 and T2 z-scores). Characterization of CMR patterns is critical for the development of noninvasive biomarkers for PHT and may decrease dependence on EMB.

Cardiac magnetic resonance diastolic indices correlate with ventricular filling pressures in pediatric heart transplant recipients.

BACKGROUND: Atrial and ventricular filling pressures are routinely used in pediatric heart transplant (PHTx) recipients to assess graft function. We hypothesized that cardiac magnetic resonance (CMR) diastolic indices correlate with filling pressures, providing a noninvasive method of hemodynamic assessment. METHODS: Pediatric heart transplant recipients were prospectively enrolled at the time of cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) were measured. CMR included standard volumetric analysis. Filling curves were calculated by contouring every phase in the short-axis stack. Global longitudinal and circumferential strain (GLS, GCS) were calculated using feature tracking. Atrial volumes and ejection fraction were calculated from 4-chamber and 2-chamber cine images. Correlations were analyzed using Spearman's Rho; modeling was performed with multivariable logistic regression. RESULTS: A total of 35 patients with a mean age of 15.5 years were included, 12 with acute rejection. The median time post-transplant was 6.2 years. Peak filling rate (PFR) and peak LV ejection rate/end-diastolic volume (PER/EDV) correlated with PCWP (rho = 0.48 p = .005, and rho = -0.35 p = .046, respectively) as did GLS and GCS (rho = 0.52 p = .002, and 0.40 p = .01). Indexed maximum and minimum left atrial (LA) volume correlated with PCWP (rho = 0.41, p = .01, rho = 0.41 p = .01), and LA ejection fraction inversely correlated with PCWP (rho = -0.40, p = .02). GLS and GCS correlated with RAP (rho = 0.55, p = .001 and rho = 0.43, p = .01). A model including LV GLS and PFR estimated PCWP ≥12 mmHg with an area under the curve of 0.84. CONCLUSIONS: Cardiac magnetic resonance can be a useful noninvasive modality to assess for signs of diastolic dysfunction after PHTx.

Dilatable Pulmonary Artery Banding Palliation in Congenital Heart Disease.

BACKGROUND: Surgical pulmonary artery banding (PAB) has been limited in practice because of later requirement for surgical removal or adjustment. The aim of this study is to describe our experience creating a dilatable PAB via transcatheter balloon dilation (TCBD) in congenital heart disease (CHD) patients. METHODS: Retrospective chart review of adjustable PAB-outline anatomical variants palliated and patient outcomes. RESULTS: Sixteen patients underwent dilatable PAB-median age 52 days (range 4-215) and weight 3.12 kg (1.65-5.8). Seven (44%) of the patients were premature, 11 (69%) had ventricular septal defect(s) with pulmonary over-circulation, four (25%) atrioventricular septal defects, and four (25%) single ventricle physiology. Subsequent to the index procedure: five patients have undergone intracardiac complete repair, six patients remain well palliated with no additional intervention, and four single ventricles await their next palliation. One patient died from necrotizing enterocolitis (unrelated to PAB) and one patient required a pericardiocentesis postoperatively. Five patients underwent TCBD of the PAB without complication-Two had one TCBD, two had two TCBD, and another had three TCBD. The median change in saturation was 14% (complete range 6-22) and PAB diameter 1.7 mm (complete range 1.1-5.2). Median time from PAB to most recent outpatient follow-up was 868 days (interquartile range 190-1,079). CONCLUSIONS: Our institution has standardized a PAB technique that allows for transcatheter incremental increases in pulmonary blood flow over time. This methodology has proven safe and effective enough to supplant other institutional techniques of limiting pulmonary blood flow in most patients-allowing for interval growth or even serving as the definitive palliation.

The Destiny of Postoperative Residual Ventricular Septal Defects After Surgical Repair in Infants and Children.

PURPOSE: Residual ventricular septal defects (rVSDs) of small size are commonly seen on transesophageal echocardiography after surgical repair. This study aimed to determine the destiny of rVSD found on intraoperative echocardiogram. METHODS: Patients undergoing surgical repair of VSD as the primary procedure with available intraoperative and discharge echocardiograms between 2007 and 2017 were reviewed. Presence of an rVSD on intraoperative echo triggered review of discharge echo and of subsequent follow-up echocardiograms. RESULTS: One hundred four patients were analyzed. The mean age and weight for the entire cohort were 1.4 ± 2.9 years (median, 5.4 months; range, 29 days to 14 years) and 8.8 ± 9.9 kg (median, 5.1 kg; range, 2.7-58 kg), respectively. Sixty (57%) patients had rVSD at discharge, with mean size of residual VSD of 1.38 ± 0.92 mm (mode, 0.6; median, 2.2 mm; range, 0.5-3.9 mm). The mean follow-up time was 3.7 ± 3.1 years (range, 1 month to 9.3 years). Among those with rVSD at discharge, a residual shunt persisted in 73% at one-month follow-up. On follow-up at three years postdischarge, of the 60 patients with early rVSD, 6 had a persistent rVSD (10%) with a mean diameter of 3.0 ± 0.8 mm (range, 2.4-3.9 mm). CONCLUSIONS: Residual VSD after surgical repair is detected frequently on postoperative echocardiogram. The presence of rVSD was not associated with any preoperative, intraoperative, or postoperative factors. By three years of follow-up, only six patients continued to demonstrate rVSD with a mean diameter of 3 mm, suggesting that defects 3 mm or greater may be less likely to close spontaneously after three years.

Correlation of gene expression profiling score, cardiac hemodynamics and echocardiographic parameters in asymptomatic, rejection-free pediatric heart transplant recipients.

OBJECTIVES: To correlate gene expression profiling scores obtained by AlloMap® with cardiac hemodynamics, cardiac allograft vasculopathy (CAV), and echocardiographic parameters in asymptomatic, rejection-free pediatric heart transplant (HT) recipients. METHODS: Single-institution retrospective study of 210 AlloMap scores obtained concomitantly with cardiac catheterization and echocardiogram from 55 children during follow-up after cardiac transplantation. RESULTS: The median age at HT was 5.1 years (range, 0.9-14.1), with 29 males and 26 females. AlloMap scores were high in <2 years vs ≥2 years of age at the time of HT (P = .001), and trending higher with time after HT (R2  = .04, P = .004). There was no significant difference in scores between ACR grades 0 and 1R or CAV. There was mild to modest correlation of AlloMap scores with the mean right atrial pressure (P = .002), and pulmonary capillary wedge pressure (P = .02), but no correlation was found with LV SF% (P = .3), LV EF% (P = .5), or RV FAC % (P = .8). CONCLUSIONS: Our study provides preliminary data that the AlloMap score must be studied carefully before it can be used in children, particularly in those under 2 years of age. Monitoring of serial scores for each patient could potentially reflect changes in allograft performance that may determine indications for catheterization and biopsy which needs to be validated in future studies.

Syncope in a Child with Pulmonary Hypertension and Positive Gene Tests for Hereditary Hemorrhagic Telangiectasia and Long QT Syndrome.

We present a 10-year-old boy with syncope who was found to have long-QT syndrome and severe Pulmonary Hypertension (PH) both in the absence of a secondary cause; to our knowledge, this is the first report with this unusual coexistence. His genetic tests were positive for hereditary hemorrhagic telangiectasia and Long QT Syndrome (LQTS) without any family history of PH or LQTS. We demonstrated that digital subtraction pulmonary angiography was more useful compared to CT angiogram to demonstrate pulmonary vascular changes which correlated with a noresponse to acute vasoreactivity testing during right heart catheterization. He has been stable for the last 2 years on Ambrisentan, Sildenafil, and Nadolol without recurrence of symptoms.

Pulmonary Vascular Underperfusion Score in Premature Infants with Bronchopulmonary Dysplasia and Pulmonary Hypertension.

Pulmonary hypertension (PH) is a complication of bronchopulmonary dysplasia (BPD). The underlying pathophysiology of BPD-associated PH is complex and poorly understood. Echocardiogram may underestimate the severity of pulmonary hypertensive vascular disease in severe BPD. Digital subtraction pulmonary angiography (DSPA) is a potentially useful imaging modality for evaluating changes in the pulmonary vasculature of BPD-associated PH. In this study, we objectively quantified the pulmonary hypertensive vascular changes demonstrated by DSPA using a novel pulmonary vascular underperfusion score (PVUS) and correlated the scoring system with echocardiography parameters and cardiac hemodynamics by right heart catheterization.

Relation Between New York Heart Association Functional Class and Objective Measures of Cardiopulmonary Exercise in Adults With Congenital Heart Disease.

We aimed to compare New York Heart Association (NYHA) functional class in adult congenital heart disease (ACHD) patients with objectively measured cardiopulmonary exercise testing (CPET) parameters. This study included retrospective review of ACHD patients who underwent a CPET between August 2014 and April 2018 at our center. Patients were grouped according to severity of CHD, and NYHA class as recorded in their medical record or estimated from the clinical narrative. A total of 175 ACHD patients (mean age 30 ± 11 years) with NYHA class I-III enrolled in the study. The NYHA functional class was II or III in most complex CHD. There was a strong inverse relation between NYHA class and peak oxygen consumption, oxygen uptake efficiency slope, and the double product at peak exercise (product of heart rate and systolic blood pressure) (p<0.0001). There was no relation between NYHA class and ventilation efficiency slope (p = 0.37). In conclusion, NYHA functional class correlates with objective measures of CPET, however there is wide variability in measured exercise capacity in each NYHA classification. Therefore, whereas NYHA class of patients is a simple measure for assessment of functional status, CPET is an important tool to identify the source of exercise limitation in ACHD patients.

Digital Subtraction Pulmonary Angiography in Children with Pulmonary Hypertension due to Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common respiratory sequelae of prematurity and histopathologically features fewer, dysmorphic, pulmonary arteries. We present our experience with the digital subtraction pulmonary angiography (DSPA) findings of a segmental vascular filling abnormality in three children who were born at extreme prematurity and have pulmonary hypertension due to severe BPD. Our preliminary data suggest that DSPA may be useful in evaluating the severity of pulmonary vascular disease in children with BPD.

Senning Procedure for Physiological Atrial Inversion With Left Atrial Isomerism.

We present the case of an infant with left atrial isomerism with complex pulmonary and systemic venous connections that resulted in physiological parallel circulation in the setting of ventriculoarterial concordance who was surgically treated using the Senning procedure. This case highlights a rare cause for cyanosis due to poor mixing from a parallel circulation and an issue with nomenclature. (Level of Difficulty: Advanced.).

Acquired and congenital coronary artery abnormalities.

Sudden unexpected cardiac deaths in approximately 20% of young athletes are due to acquired or congenital coronary artery abnormalities. Kawasaki disease is the leading cause for acquired coronary artery abnormalities, which can cause late coronary artery sequelae including aneurysms, stenosis, and thrombosis, leading to myocardial ischaemia and ventricular fibrillation. Patients with anomalous left coronary artery from the pulmonary artery can develop adequate collateral circulation from the right coronary artery in the newborn period, which remains asymptomatic only to manifest in adulthood with myocardial ischaemia, ventricular arrhythmias, and sudden death. Anomalous origin of coronary artery from the opposite sinus occurs in 0.7% of the young general population aged between 11 and 15 years. If the anomalous coronary artery courses between the pulmonary artery and the aorta, sudden cardiac death may occur during or shortly after vigorous exercise, especially in patients where the anomalous left coronary artery originates from the right sinus of Valsalva. Symptomatic patients with evidence of ischaemia should have surgical correction. No treatment is needed for asymptomatic patients with an anomalous right coronary artery from the left sinus of Valsalva. At present, there is no consensus regarding how to manage asymptomatic patients with anomalous left coronary artery from the right sinus of Valsalva and interarterial course. Myocardial bridging is commonly observed in cardiac catheterisation and it rarely causes exercise-induced coronary syndrome or cardiac death. In symptomatic patients, refractory or ß-blocker treatment and surgical un-bridging may be considered.

Takotsubo cardiomyopathy: an unusual cardiomyopathy at an unusual age.

We describe an atypical presentation of stress-induced cardiomyopathy - Takotsubo cardiomyopathy - in a 16-month-old boy previously diagnosed with cyclic vomiting and episodic hypertension. He developed features of cardiac failure and his echocardiogram showed left ventricular wall motion abnormality accompanied with elevated cardiac enzymes. Cardiac catheterisation showed no coronary arterial abnormality. Complete spontaneous recovery occurred 2 weeks after admission.

Preliminary experience with cardiac reconstruction using decellularized porcine extracellular matrix scaffold: human applications in congenital heart disease.

An ideal material for repair of congenitally malformed hearts would encourage tissue regeneration with growth potential. Decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) promotes tissue regeneration in animal models and noncardiac human applications. This retrospective review evaluates SIS-ECM for reconstruction of congenital heart defects. From June 2007 to May 2009, SIS-ECM patches were used in 43 operations on 40 patients aged 2 days to 13 years. In 16 cases, the SIS-ECM was used for pericardial closure. The SIS-ECM was used for cardiac or great vessel repair in 37 cases: atrial septal defect repair in 11, pulmonary arterioplasty in 10, right ventricular outflow tract patch in 6, pulmonary monocusp valve creation in 5, superior vena cava patch in 2 and aortoplasty in 2, valve leaflet augmentation in 2, and repair of unroofed coronary sinus in 1. Follow-up was complete. There were 5 deaths, all unrelated to the SIS-ECM. Mean follow-up was 7.85 months (0.5-24 months). No pericardial effusions or intracardiac or intravascular thromboses occurred related to the SIS-ECM. The patches did not shrink or calcify. Four of 5 monocusp valves were competent and none were stenotic. One patient who underwent tricuspid valve anterior leaflet augmentation with SIS-ECM required tricuspid valve replacement 4 months later for severe regurgitation following a catheter-based procedure. Explanted tissue showed resorption of the SIS-ECM, replacement with organized collagen, and re-endothelialization. Repair of congenital heart defects using SIS-ECM is feasible and safe. In valve reconstruction, this procedure shows potential for replacement by autologous tissue. Longer-term follow-up is required to assess the potential for growth.

Long-term outcome of palliation with internal pulmonary artery bands after primary heart transplantation for hypoplastic left heart syndrome.

The purpose of this study was to describe the long-term outcome of infants with hypoplastic left heart syndrome (HLHS) who underwent placement of internal pulmonary artery bands as part of a transcatheter palliation procedure followed by primary heart transplantation. Transcatheter palliation included stenting of the ductus arteriosus, decompression of the left atrium by atrial septostomy, and internal pulmonary artery band placement. Cardiac hemodynamics, pulmonary artery architecture, and pulmonary artery growth since transplantation are described. Nine infants with HLHS had internal pulmonary artery bands placed and underwent successful heart transplant. No infant required reconstruction of the pulmonary arteries at the time of transplant. At 1 year after transplant, all of the recipients had normal mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient. Pulmonary angiography performed at 1 year after transplant demonstrated no distortion of pulmonary artery anatomy with significant interval growth of the branch pulmonary arteries. There was 100% survival to hospital discharge after transplant in this cohort of infants. Transcatheter placement of internal pulmonary artery bands for HLHS offers protection of the pulmonary vascular bed while preserving pulmonary artery architecture and growth with good long-term outcome.

On-line multi-slice computed tomography interactive overlay with conventional X-ray: a new and advanced imaging fusion concept.

BACKGROUND: Computed tomography (CT) has revolutionized noninvasive cardiovascular evaluations. Complicated percutaneous procedures require precise imaging guidance that conventional X-ray is often unable to provide. By combining X-ray imaging with real-time, interactive, CT-based landmarks, interventional procedures could be facilitated. We describe two cases using the first CT/Live X-ray overlay in which this technology shows its potential. CASE REPORTS: A 31-year-old male with an anatomically complicated atrial septal defect (ASD) was referred for percutaneous closure. Transesophageal echocardiography (TEE) revealed an inferior location of the ASD complicated by it's proximity to a prominent Eustachian ridge. The CT was used to create a patient-specific physical model in preparation for the procedure and an in-lab real-time CT overlay allowing successful closure. A second case of a 41-year-old male with coronary artery disease status-post coronary artery bypass, aortic valve replacement (AVR), and aortic root replacement with an abnormal coronary computed tomography angiogram (CTA). In a prior procedure years ago the saphenous vein graft (SVG) to the left anterior descending artery (LAD) could not be cannulated during invasive angiography, given the patient's complicated and unusual anatomy. Using CT overlay, the superiorly and anteriorly located SVG was cannulated successfully. DISCUSSION: CT/Live X-ray overlay provided an adequate anatomical intra-procedural ASD evaluation, defect sizing, and guidance in one case and localization of an anatomically challenging graft ostium in the other case. Adding the CT landmarks as an overlay to traditional X-ray techniques provides a revolutionary and advanced imaging fusion concept that should improve procedural success.

Sildenafil Increases Systemic Saturation and Reduces Pulmonary Artery Pressure in Patients with Failing Fontan Physiology.

OBJECTIVE: The purpose of this study was to investigate the effect of sildenafil in patients with failing Fontan physiology. DESIGN: A retrospective chart review was performed to compare history and available data in patients with Fontan circulations before and after starting sildenafil. The paired and unpaired Student's t-tests were used for statistical analyses. PATIENTS: Six patients at our institution with Fontan physiology, persistent symptoms of cyanosis or effusion, and poor hemodynamics as measured in the catheterization laboratory were placed on sildenafil. One patient was not included in the analysis because of insufficient length of treatment. All patients had symptoms of failing Fontan hemodynamics with either persistent cyanosis or effusions. In this group, the mean pulmonary artery pressure was greater than 15 mm Hg (17.4 ± 1.5 mm Hg) with mean estimated pulmonary vascular resistance of 3.5 ± 1.0 Wood units × m(2) prior to starting sildenafil. RESULTS: Sildenafil significantly increased the systemic arterial oxyhemoglobin saturation in this group (82.8 ± 7.3% pre-treatment vs. 91.0 ± 5.5% post-treatment, P = .017). In the four out of five patients who have had follow-up catheterizations, there was a significant decrease in pulmonary artery pressure (17.4 ± 1.5 mm Hg pre-treatment vs. 13.8 ± 2.1 mm Hg post-treatment, P = .018) and in estimated pulmonary vascular resistance pre- and post-sildenafil treatment (3.5 ± 1.0 Wood units × m(2) pre-treatment vs. 2.0 ± 0.4 Wood units × m(2) post-treatment, P = .031). CONCLUSIONS: Sildenafil may be a useful adjunct to therapy in patients with failing Fontan physiology likely through its function as a pulmonary vasodilator.

Interventional cardiac catheterization procedures in pediatric cardiac transplant patients: transplant surgery is not the end of the road.

OBJECTIVES: The objectives of this study are to report the spectrum of cardiac lesions in pediatric patients post-orthotopic heart transplantation (OHT), the characteristics of patients who develop these lesions, and the feasibility of transcatheter intervention in treating these lesions. BACKGROUND: Indications for OHT in the pediatric population range from cardiomyopathy to complex congenital heart defects with and without prior palliation. These patients may have residual vascular access and great vessel abnormalities. METHODS: Data was collected through retrospective review of all OHT patients at our institution from 1988 to 2005. RESULTS: During the study period, 276 heart transplants were performed. Forty-seven patients, age 1.6 [0.1-26] years with a weight of 9.5 [3.5-96.0] kilograms, underwent 69 procedures. Patients with original diagnoses of hypoplastic left heart syndrome and failed palliations required intervention most frequently. Sixteen patients, all with a history of left sided disease, developed aortic arch obstruction. Fifteen were successfully treated with balloon angioplasty while one has recurrent supravalve aortic obstruction. Fourteen patients had superior vena cava obstruction treated with balloon angioplasty and/or stent placement. Twelve patients required no further intervention and two required further stent placement. Ilio-femoral vein occlusion was treated with balloon angioplasty alone in 4 patients and stent placement in 10 patients to achieve vessel patency. Other procedures included treatment of branch pulmonary artery and pulmonary vein stenosis. CONCLUSION: Anastomotic aortic arch and venous obstructive lesions should be sought following pediatric OHT as they occur in almost 20% of patients and can be successfully addressed using interventional techniques.

Aortic pseudo aneurysm complicating coarctation stenting successfully treated with a PTFE balloon expandable covered stent.

Percutaneous stenting of both native and recurrent coarctation of the aorta has become an acceptable alternative to surgical repair in most centers throughout the world. Severe complications such as aortic rupture, dissection, and late pseudo aneurysm formation are rare but worrisome complications. In many countries, commercially available balloon expandable covered stents designed for intravascular use are used either for primary stenting, or in treating complications once identified. These endovascular stents, however, are not available in the United States. We report the use of a commercially available covered stent, which has been approved by the Food and Drug Administration for tracheal use, to exclude an aortic pseudo aneurysm that was identified late after stenting a native coarctation.