Hythem Nawaytou

Biomarkers in pediatric heart disease

A biomarker is a characteristic that can be used as an indicator of a biological state. A biomarker can be a clinical observation, laboratory test or an imaging parameter. In this review, we discuss the use of biomarkers in differentiating cardiac from noncardiac disease; predicting the prognosis of patients with heart failure, pulmonary hypertension and dilated cardiomyopathy; diagnosing subclinical cardiac involvement in muscular dystrophy and postchemotherapy cancer patients; detecting acute rejection following heart transplantation; diagnosing Kawasaki disease; aiding the management of postoperative cardiac patients; and managing both common (tetralogy of Fallot) and complex (single-ventricle physiology) congenital heart diseases.

Left Ventricular Rotational Mechanics in Children After Heart Transplantation

Background—Left ventricular (LV) dysfunction after orthotopic heart transplantation (OHT) is multifactorial and can be an indicator of graft rejection or coronary artery vasculopathy. Analysis of rotational mechanics may help in the early diagnosis of ventricular dysfunction. Studies describing the left ventricular rotational strain in children after OHT are lacking. It is important to establish the baseline rotational mechanics in pediatric OHT to pursue further studies in this population. Methods and Results—Rotational strain measured by speckle tracking was compared in 32 children after OHT, with no evidence of active rejection or coronary artery vasculopathy with 35 age-matched normal controls. Twelve OHT patients and 13 controls underwent moderate exercise with pre- and postexercise echocardiography. Torsion, slope of the systolic limb of the torsion–radial displacement loop, and the untwist rate were significantly higher in OHT patients (torsion: median 2.7°/cm [Q1–Q3, 2.3–3.2] versus 2.3°/cm [Q1–Q3, 1.9–2.7]; P=0.03, torsion–radial displacement loop: 2.7°/mm [Q1–Q3, 2.1–3.6] versus 2.0°/mm [Q1–Q3, 1.6–2.7]; P=0.008, indexed peak untwist rate: −21.6°/s/cm [Q1–Q3, −24.3 to −15.7] versus −17.1°/s/cm [Q1–Q3, −19.6 to −13.3]; P=0.01). Contrary to controls, OHT recipients were unable to increase torsion with exercise (OHT: 2.8°/cm [2.7–3.2] versus 3°/cm [2.4–3.5]; P=0.81, controls: 2.2°/cm [2–2.6] versus 3°/cm [2.4–3.7]; P=0.01, pre and post exercise, respectively). The systolic slope of the torsion–radial displacement loop relationship decreased with exercise in most OHT patients. Conclusions—Baseline rotational strain in OHT patients is higher than normal with a blunted response to exercise. The slope of torsion–radial displacement loop, and its response to exercise, may serve as a marker of left ventricular dysfunction in OHT patients.

Right Ventricular Systolic-to-Diastolic Time Index: Hypoplastic Left Heart Fetuses Differ Significantly from Normal Fetuses

BACKGROUNDnA growing body of evidence indicates that right ventricular dysfunction in patients with palliated hypoplastic left heart syndrome (HLHS) originates in fetal life. In this study, the systolic-to-diastolic time index (SDI) was used to study the presence of ventricular dysfunction in single right ventricles in fetuses with HLHS or evolving HLHS and to assess whether this dysfunction is related to increase preload, myocardial performance, or interventricular interaction.nnnMETHODSnEchocardiograms from 78 fetuses with HLHS and 10 with evolving HLHS were retrospectively compared with those of 78 normal control fetuses. Fetuses with HLHS were further grouped according to morphology of the left ventricle (LV): not visible (nxa0=xa035) or visible (nxa0=xa043). Spectral Doppler signals obtained from right ventricular inflow (blood pool) and tissue Doppler from the tricuspid lateral annulus were analyzed. The SDI was calculated as the ratio of the ejection time plus isovolumic contraction and relaxation times to the diastolic filling time. E/A and E/e ratios, cardiac output, preload index, and Tei index were also calculated.nnnRESULTSnFetuses with HLHS demonstrated significantly elevated right ventricular SDI values by both blood pool Doppler and Doppler tissue imaging compared with control subjects (1.89xa0±xa00.33 vs 1.58xa0±xa00.29 [Pxa0<xa0.001] and 2.1xa0±xa00.57 vs 1.66xa0±xa00.31 [Pxa0<xa0.001], respectively). Changes in filling time rather than ejection time predominated. Fetuses with HLHS with visible LVs and those with evolving HLHS had significantly higher SDI values than fetuses with HLHS without visible LVs (no visible LV, 1.75xa0±xa00.22; visible LV, 2xa0±xa00.36; Pxa0=xa0.001; evolving HLHS, 2.19xa0±xa00.68; Pxa0<xa0.001). SDI was correlated with the Tei index (Rxa0=xa00.58) and was more sensitive than the Tei index in identifying differences between the HLHS subgroups.nnnCONCLUSIONSnFetuses with evolving and overt HLHS exhibit abnormally increased SDI values in utero. This difference is likely related to inherently pathologic interventricular interactions and/or diastolic dysfunction of the right ventricle in fetuses with HLHS.

Diagnostic value of myocardial deformation pattern in children with noncompaction cardiomyopathy

The current echocardiographic diagnostic criteria for noncompaction cardiomyopathy (NCC) have variable sensitivity and low specificity. Moreover, there are limited data on the use of myocardial deformation imaging for early detection of myocardial dysfunction in children with NCC. We describe left ventricular (LV) deformation patterns in children with NCC, with the goal of identifying a potential diagnostic pattern. We prospectively enrolled 30 children with NCC (47% male; mean age 7.2xa0years) and 30 age- and gender-matched controls. Extent and severity of non compaction in each segment were evaluated in LV 16-segment model. Regional (base, mid and apex) and segmental (16 segments) longitudinal strain (LS), circumferential strain (CS) and radial strain (RS) were measured using speckle tracking echocardiography. In all patients with NCC, regional and segmental CS and RS at the apex were significantly decreased compared to controls (CS apex: −u200919.2u2009±u20095.4% vs. −u200930.2u2009±u20096.9%, pu2009<u20090.001/RS apex: 23.5u2009±u20098.6% vs. 44.1u2009±u200914.5%, pu2009<u20090.001). Thirty percent (9/30) of patients had an EFu2009<u200950%. In these patients, there was additional decrease in CS in basal segments and in LS in basal, mid-cavity and apical segments (CS base: −u200916.4u2009±u20094.7% vs. −u200924.6u2009±u20093.9%, pu2009<u20090.001/LS (average all LV segments): −u200913.9u2009±u20093.1% vs. −u200920.7u2009±u20094.7%, pu2009<u20090.001). A cut-off value of CS at the apex of −u200924.5% was a strong differentiating feature between patients with NCC and EFu2009>u200950% and controls (sensitivity: 87%, specificity 79%, AUC 0.88, pu2009<u20090.001). Children with NCC exhibit a deformation pattern characterized by decreased apical circumferential strain, which may serve as a potential diagnostic tool for NCC. The role of decreased global LV longitudinal and basal circumferential strain should be further evaluated as a potential prognostic tool.

Pushing the envelope: a treat and repair strategy for patients with advanced pulmonary hypertension associated with congenital heart disease:

Pulmonary arterial hypertension (PAH) is a frequent complication of congenital heart disease as a consequence of altered pulmonary hemodynamics with increased pulmonary blood flow and pressure. The development of pulmonary vascular disease (PVD) in this patient population is an important concern in determining operative strategy. Early, definitive surgical repair, when possible, is the best therapy to prevent and treat PVD. However, this is not possible in some patients because they either presented late, after the development of PVD, or they have complex lesions not amenable to one-step surgical correction, including patients with single ventricle physiology, who have a continuing risk of developing PVD. These patients represent an important, high-risk subgroup and many have been considered inoperable. We present a case series of two patients with complex congenital heart disease and advanced PVD who successfully underwent a treat and repair strategy with aggressive PAH therapies before surgical correction. Both patients had normalization of pulmonary vascular resistance prior to surgical correction. Caution is warranted in applying this strategy broadly and long-term follow-up for these patients is crucial. However, this treat and repair strategy may allow for favorable outcomes among some patients who previously had no therapeutic options.

Biomarkers of cardiac function and outcome in univentricular congenital heart disease

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Current Biomarker Findings 2014:4 53–59 Current Biomarker Findings Dovepress

Pulmonary veno-occlusive disease in a pediatric hematopoietic stem cell transplant patient: a cautionary tale

M. S. Zinter , A. Melton, A. J. Sabnis, C. C. Dvorak, B. M. Elicker, H. M. Nawaytou, R. J. Kameny and J. R. Fineman Benioff Children’s Hospital, University of California, San Francisco, CA, USA; Department of Pediatrics, Division of Critical Care Medicine, University of California, San Francisco, CA, USA; Department of Pediatrics, Division of Allergy, Immunology, and Blood and Marrow Transplantation, University of California, San Francisco, CA, USA; Department of Pediatrics, Division of Hematology and Oncology, University of California, San Francisco, CA, USA; Department of Radiology, University of California, San Francisco, CA, USA; Department of Pediatrics, Division of Cardiology, University of California, San Francisco, CA, USA

A Preliminary Study of Left Ventricular Rotational Mechanics in Children with Noncompaction Cardiomyopathy: Do They Influence Ventricular Function?

Background: Current diagnostic criteria for noncompaction cardiomyopathy (NCC) lack specificity, and the disease lacks prognostic indicators. Reverse apical rotation (RAR) with abnormal rotation of the cardiac apex in the same clockwise direction as the base has been described in adults with NCC. The aim of this study was to test the hypothesis that RAR might differentiate between symptomatic NCC and benign hypertrabeculations and might be associated with ventricular dysfunction. Methods: Echocardiograms from 28 children with NCC without cardiac malformations were prospectively compared with those from 29 age‐matched normal control subjects. A chart review was performed to identify the patients’ histories and clinical characteristics. Speckle‐tracking was used to measure longitudinal strain, circumferential strain, and rotation. Results: RAR occurred in 39% of patients with NCC. History of left ventricular (LV) dysfunction or arrhythmia was universal in, but not exclusive to, patients with RAR. Patients with RAR had lower LV longitudinal strain but similar ejection fractions compared with patients without RAR (median, ‐15.6% [interquartile range, ‐12.9% to ‐19.3%] vs ‐19% [interquartile range, ‐14.5% to ‐21.9%], P < .01; 53% [interquartile range, 43% to 68%] vs 61% [interquartile range, 58% to 67%], P = .08). Only a pattern of contraction with RAR, early arrest of twisting by mid‐systole, and premature untwisting was associated with lower ejection fraction (46%; interquartile range, 43% to 52%; P = .006). Conclusions: RAR is not a sensitive but is a specific indicator of complications in children with NCC. Therefore, RAR may have prognostic rather than diagnostic value. Premature untwisting of the left ventricle during ejection may be an even more worrisome indicator of LV dysfunction. HIGHLIGHTSRotational mechanics in children with noncompaction cardiomyopathy were studied.RAR in the clockwise direction occurred in 40% of children.Left ventricular dysfunction, heart failure, and arrhythmias were associated with RAR.Patients with premature untwisting during ejection had decreased ejection fraction.RAR is possibly related to dysfunction of the apical compacted layer of myocardium.

Intraoperative transesophageal echocardiographic predictors of recurrent left ventricular outflow tract obstruction in children undergoing subaortic stenosis resection

Intraoperative transesophageal echocardiography (iTEE) is used to assess for residual left ventricular outflow tract obstruction (LVOTO) after surgical resection of subaortic membrane causing subaortic stenosis (sub‐AS). We aimed to identify the iTEE features associated with recurrence of LVOTO.

Postablation Right Atrial Dissection in Ebstein's Anomaly

Graphical abstract