Catherine M. Avitabile

Lean mass deficits, vitamin D status and exercise capacity in children and young adults after Fontan palliation

Objective We sought to evaluate body composition in children and young adults with Fontan physiology. Leg lean mass (LM) deficits correlate with diminished exercise capacity in other populations and may contribute to exercise limitations in this cohort. Methods This cross-sectional study included whole body dual energy X-ray absorptiometry scans in 50 Fontan participants ≥5 years, and measures of peak oxygen consumption (VO2) in 28. Whole body and leg LM (a measure of skeletal muscle) were converted to sex- and race-specific Z-scores, relative to age and stature, based on 992 healthy reference participants. Results Median age was 11.5 (range 5.1–33.5) years at 9.3 (1.1–26.7) years from Fontan. Height Z-scores were lower in Fontan compared with reference participants (−0.47±1.08 vs 0.25±0.93, p<0.0001). Body mass index Z-scores were similar (0.15±0.98 vs 0.35±1.02, p=0.18). LM Z-scores were lower in Fontan compared with reference participants (whole body LM −0.33±0.77 vs 0.00±0.74, p=0.003; leg LM −0.89±0.91 vs 0.00±0.89, p<0.0001). LM Z-scores were not associated with age or Fontan characteristics. Leg LM Z-scores were lower in vitamin D deficient versus sufficient Fontan participants (−1.47±0.63 vs −0.71±0.92, p=0.01). Median per cent predicted peak VO2 was 81% (range 13%–113%) and was associated with leg LM Z-scores (r=0.54, p=0.003). Conclusions Following Fontan, children and young adults are shorter than their peers and have significant LM deficits. Skeletal muscle deficits were associated with vitamin D deficiency and reduced exercise capacity. Future studies should examine the progression of these deficits to further understand the contribution of peripheral musculature to Fontan exercise capacity.

Deficits in bone density and structure in children and young adults following Fontan palliation.

BACKGROUND Survival of patients with congenital heart disease has improved such that there are now more adults than children living with these conditions. Complex single ventricle congenital heart disease requiring Fontan palliation is associated with multiple risk factors for impaired bone accrual. Bone density and structure have not been characterized in these patients. METHODS Tibia peripheral quantitative computed tomography (pQCT) was used to assess trabecular and cortical volumetric bone mineral density (vBMD), cortical dimensions, and calf muscle area in 43 Fontan participants (5-33 years old), a median of 10 years following Fontan palliation. pQCT outcomes were converted to sex- and race-specific Z-scores relative to age based on >700 healthy reference participants. Cortical dimensions and muscle area were further adjusted for tibia length. RESULTS Height Z-scores were lower in Fontan compared to reference participants (mean ± SD: -0.29 ± 1.00 vs. 0.25 ± 0.93, p < 0.001); BMI Z-scores were similar (0.16 ± 0.88 vs. 0.35 ± 1.02, p = 0.1). Fontan participants had lower trabecular vBMD Z-scores (-0.85 ± 0.96 vs. 0.01 ± 1.02, p < 0.001); cortical vBMD Z-scores were similar (-0.17 ± 0.98 vs. 0.00 ± 1.00, p = 0.27). Cortical dimensions were reduced with lower cortical area (-0.59 ± 0.84 vs. 0.00 ± 0.88, p<0.001) and periosteal circumference (-0.50 ± 0.82 vs. 0.00 ± 0.84, p < 0.001) Z-scores, compared to reference participants. Calf muscle area Z-scores were lower in the Fontan participants (-0.45 ± 0.98 vs. 0.00 ± 0.96, p = 0.003) and lower calf muscle area Z-scores were associated with smaller periosteal circumference Z-scores (R = 0.62, p < 0.001). Musculoskeletal deficits were not associated with age, Fontan characteristics, parathyroid hormone or vitamin D levels. CONCLUSIONS Children and young adults demonstrate low trabecular vBMD, cortical structure and muscle area following Fontan. Muscle deficits were associated with smaller periosteal dimensions. Future studies should determine the fracture implications of these deficits and identify interventions to promote musculoskeletal development.

A Multifaceted Approach to the Management of Plastic Bronchitis After Cavopulmonary Palliation

BACKGROUND Plastic bronchitis is a rare, potentially life-threatening complication after Fontan operation. Hemodynamic alterations (elevated central venous pressure and low cardiac output) likely contribute to the formation of tracheobronchial casts composed of inflammatory debris, mucin, and fibrin. Pathologic studies of cast composition support medical treatment with fibrinolytics such as inhaled tissue plasminogen activator (t-PA). METHODS This was a retrospective case series of medical, surgical, and catheter-based treatment of patients with plastic bronchitis after cavopulmonary palliation. RESULTS Included were 14 patients (86% male, 93% white). Median age at Fontan operation was 2.7 years (range, 1.2 to 4.1 years), with median interval to plastic bronchitis presentation of 1.5 years (range, 9 days to 15.4 years). Cast composition was available for 11 patients (79%) and included fibrin deposits in 7. All patients were treated with pulmonary vasodilators, and 13 (93%) were treated with inhaled t-PA. Hemodynamically significant lesions in the Fontan pathway were addressed by catheter-based (n=9) and surgical (n=3) interventions. Three patients (21%) underwent heart transplantation. Median follow-up was 2.7 years (range, 0.6 to 8.7 years). Symptoms improved, such that 6 of 13 patients (46%) were weaned off t-PA. Rare or episodic casts are successfully managed with outpatient t-PA in most of the other patients. Of the 3 patients who underwent heart transplant, 2 are asymptomatic and 1 has recurrent casts in the setting of elevated filling pressures and rejection. CONCLUSIONS A systematic step-wise algorithm that includes optimization of hemodynamics, aggressive pulmonary vasodilation, and inhaled t-PA is an effective treatment strategy for patients with plastic bronchitis after cavopulmonary connection.

Usefulness of Insulinlike Growth Factor 1 as a Marker of Heart Failure in Children and Young Adults After the Fontan Palliation Procedure

Growth hormone and its mediator, insulinlike growth factor 1 (IGF-1), are key determinants of growth in children and young adults. As patients with Fontan physiology often experience diminished longitudinal growth, we sought to describe IGF-1 levels in this population and to identify factors associated with IGF-1 deficiency. Forty-one Fontan subjects ≥5 years were evaluated in this cross-sectional study. Age- and gender-specific height Z scores were generated using national data. Laboratory testing included IGF-1 and brain natriuretic peptide (BNP) levels. IGF-1 levels were converted to age-, gender-, and Tanner stage-specific Z scores. BNP levels were log transformed to achieve a normal distribution (log-BNP). Medical records were reviewed for pertinent clinical variables. Predictors of IGF-1 Z score were assessed through the Student t test and Pearsons correlation. Median age was 11.1 years (range 5.1 to 33.5 years), and time from Fontan was 8.2 years (1.1 to 26.7). Mean height Z score was -0.2 ± 0.9 with a mean IGF-1 Z score of -0.1 ± 1.3. There was no association between IGF-1 Z score and height Z score. Longer interval since Fontan (R = -0.32, p = 0.04), higher log-BNP (R = -0.40; p = 0.01), and lower indexed systemic flow on cardiac magnetic resonance (R = 0.55, p = 0.02) were associated with lower IGF-1 Z scores. In conclusion, in this cohort with Fontan physiology, higher BNP and lower systemic flow were associated with lower IGF-1 Z score. Longitudinal studies are needed to determine if these relations represent a mechanistic explanation for diminished growth in children with this physiology and with other forms of congenital heart disease.

Cardiac Magnetic Resonance Characterizes Myocarditis in a 16-Year-Old Female With Lyme Disease

Myocarditis may occur during early disseminated Lyme disease. A 16-year-old girl with serologic evidence of Borrelia burgdorferi infection and transient first-degree atrioventricular block underwent cardiac magnetic resonance imaging, which demonstrated myocardial hyperemia, edema, and delayed gadolinium enhancement. We discuss the use of T1- and T2-weighted dark blood sequences in addition to inversion recovery delayed enhancement imaging to support the diagnosis of Lyme myocarditis.

High-Resolution, Contrast-Enhanced Cardiac Magnetic Resonance Detects an Intracardiac Thrombus in a Fontan Patient.

A 28-year-old male with Fontan physiology presented with chest pain, elevated troponin, regional dyskinesis, and an apical echogenicity in the right-sided morphologically left ventricle (LV) on echocardiogram. Cardiac magnetic resonance (CMR) imaging was performed with a three-dimensional respiratory-navigated inversion recovery FLASH (low flip angle, spoiled gradient echo technique) sequence during slow gadolinium infusion. A hypointense lesion in the LV apex was consistent with thrombus. Gadolinium-delayed enhancement imaging demonstrated increased signal in the mid-inferior LV free wall. In this case, progressive decline in ventricular function was likely followed by an intracardiac thrombus and embolic myocardial infarction. The CMR was instrumental in characterizing the mass and identifying myocardial scar.

Accuracy and Internal Consistency of Cardiac Magnetic Resonance Imaging in Measuring Branch Pulmonary Artery Flows in Patients With Conotruncal Anomalies and Branch Pulmonary Artery Stents

Clinicians use branch pulmonary artery (BPA) blood flow distribution to help determine the need for intervention. Although phase-contrast magnetic resonance (PCMR) flow measurements are accurate, this has never been shown in the vicinity of a BPA ferromagnetic stent (FS) which produces significant susceptibility artifact. We retrospectively reviewed 49 consecutive PCMR studies performed from 2005 to 2012 on patients with repaired conotruncal anomalies and either left (n = 29) or right PA (n = 20) stents. Three methods of measuring the stented BPA flow were compared: (1) main PA (MPA) minus nonstented BPA, (2) direct PCMR of stented BPA away from the artifact, and (3) pulmonary venous flows (ipsilateral to stented BPA and derived pulmonary blood flow ratio from bilateral pulmonary venous flows). Internal consistency was tested with the Student t test, linear regression, Bland-Altman analysis, and intraclass correlation (ICC). The mean age was 11.7 ± 6.9 years with 5.8 ± 4.2 years between stent placement and CMR. There was good agreement without significant difference between MPA-derived stented BPA flow (method 1) and direct PCMR of stented BPA (method 2; 41 ± 19% vs 39 ± 19%, p = 0.59; R(2) = 0.84, p <0.001; ICC = 0.96). There was also good agreement between methods 1 and 2 compared to pulmonary venous flows, with the highest correlation occurring between method 2 and ipsilateral pulmonary venous flow (R(2) = 0.90, p <0.001; ICC = 0.97 for MPA-derived-stented BPA flow; R(2) = 0.94, p <0.001; ICC = 0.98 for direct PCMR of stented BPA). Eleven of the 49 patients (22%) underwent interventional catheterization after PCMR. In conclusion, in the vicinity of a BPA FS, accurate measurement of the net fractional pulmonary blood flow ratio is feasible. PCMR adjacent to the stent and ipsilateral pulmonary venous flows provide the most internally consistent data. These data underscore PCMRs utility in managing patients with implanted FS.

Leg lean mass correlates with exercise systemic output in young Fontan patients

Objective We previously described lower leg lean mass Z-scores (LLMZ) in Fontan patients associated with worse peak oxygen consumption on metabolic exercise testing. We hypothesised that LLMZ correlates with indexed systemic flow (Qsi) and cardiac index (CI) on exercise cardiac magnetic resonance (eCMR). Methods Thirteen patients had LLM measured by dual-energy X-ray absorptiometry within mean 40 (range 0–258) days of eCMR. LLM was converted to sex and race-specific Z-scores based on healthy reference data. Ventricular volumes and flow measurements of the ascending and descending (DAO) aorta and superior vena cava (SVC) were obtained by CMR at rest and just after supine ergometer exercise to a heart rate associated with anaerobic threshold on prior exercise test. Baseline and peak exercise measures of Qsi (SVC+DAO/BSA) and CI, as well as change in Qsi and CI with exercise, were compared with LLMZ by linear regression. Results LLMZ was not correlated with resting flows, stroke volume or CI. There was a strong linear correlation between LLMZ and change in both CI (r=0.77, p=0.002) and Qsi (r=0.73, p=0.005) from rest to exercise. There was also a significant correlation between LLMZ and Qsi at exercise (r=0.70, p=0.008). The correlation between LLMZ and CI at exercise did not reach significance (r=0.3, p=0.07). Conclusions In our cohort, there was a strong linear correlation between LLMZ and change in both CI and Qsi from rest to exercise, suggesting that Fontan patients with higher LLMZ may be better able to augment systemic output during exercise, improving performance.

Accuracy of Phase-Contrast Velocity Mapping Proximal and Distal to Stent Artifact During Cardiac Magnetic Resonance Imaging

Little data are available on the accuracy of phase-contrast magnetic resonance imaging (PC-MRI) velocity mapping in the vicinity of intravascular metal stents other than nitinol stents. Therefore, we sought to determine this accuracy using in vitro experiments. An in vitro flow phantom was used with 3 stent types: (1) 316L stainless steel, (2) nitinol self-expanding, and (3) platinum-iridium. Steady and pulsatile flow was delivered with a magnetic resonance imaging-compatible pump (CardioFlow 5000, Shelley Medical, London, Ontario, Canada). Flows were measured using a transit time flow meter (ME13PXN, Transonic, Inc, Ithaca, New York). Mean flows ranged from 0.5 to 7 L/min. For each condition, 5 PC-MRI acquisitions were made: within the stent, immediately adjacent to both edges of the stent artifact, and 1 cm upstream and downstream of the artifact. Mean PC-MRI flows were calculated by segmenting the tube lumen using clinical software (ARGUS, Siemens, Inc, Erlangen, Germany). PC-MRI and flow meter flows were compared by location and stent type using linear regression, Bland-Altman, and intraclass correlation (ICC). PC-MRI flows within the stent artifact were inaccurate for all stents studied, generally underestimating flow meter-measured flow. Agreement between PC-MRI and flow meter-measured flows was excellent for all stent types, both immediately adjacent to and 1 cm away from the edge of the stent artifact. Agreement was highest for the platinum-iridium stent (R = 0.999, ICC = 0.999) and lowest for the nitinol stent (R = 0.993, ICC = 0.987). In conclusion, PC-MRI flows are highly accurate just upstream and downstream of a variety of clinically used stents, supporting its use to directly measure flows in stented vessels.

Relationship between leg lean mass Z-score and cardiac output at exercise as measured by exercise cardiac magnetic resonance imaging

Background We previously showed that leg lean mass Z-score (LLMZ) correlates with metabolic exercise performance in Fontan patients. However, the mechanism by which leg lean mass influences exercise is not clear since LLMZ does not correlate with ventricular function or cardiac output at rest. We hypothesized that LLMZ would correlate with cardiac output at exercise and the change in cardiac output from rest to exercise. Methods Thirteen patients had leg lean mass measured by dual energy x-ray absorptiometry within mean of 40 (range 0-258) days of completing an exercise cardiac magnetic resonance (CMR) protocol. LLMZs were generated from healthy reference data. Ventricular volumes and phase contrast flow measurements (all indexed to body surface area) of the ascending (Ao) and descending (DAo) aorta, and superior vena cava (SVC) were obtained by CMR at rest and just after supine ergometer exercise to a heart rate associated with anaerobic threshold (determined by previous metabolic exercise test). Change in systemic flow (Qs = SVC + DAo) and indexed ventricular output (CI) during exercise, as well as baseline and peak exercise measures of Qs and CI were compared to LLMZ by linear regression.