QT Prolongation After Minor Head Trauma in a Pediatric Patient Abstract We report a case of QTc prolongation associated with mild concussion in a pediatric patient. An 11-year-old male presented to the emergency department after sustaining a head injury during football practice. He complained of headache and blurry vision. Physical examination was within normal apart from an irregular heart rhythm. Electrocardiogram (ECG) showed normal sinus rhythm with QTc (Bazett formula) 460 ms. The patient was diagnosed with concussion and referred for cardiology follow-up of the QTc. ECG the next day showed QTc 462 ms (heart rate 105 bpm) supine and 494 ms after suddenly standing up (heart rate 120 bpm). Family history was negative for sudden cardiac events. Exercise stress testing 1 week later showed a baseline QTc 462 ms and 488 ms at 4 min into recovery. Holter monitoring showed evidence of increased parasympathetic activity manifested by marked sinus arrhythmia. Repeated ECG, exercise stress testing, and Holter monitoring 3 months later showed normalized QTc values. His concussion symptoms were resolved at the time of repeat testing. Mild head trauma/concussion could be associated with prolonged QTc and abnormal cardiac repolarization. While these changes seem to be self-limiting, they remain a possible substrate for malignant arrhythmias. Recognition of these changes would lead to appropriate reassurance and/or precautions in the acute setting, especially in at-risk populations such as long QT syndrome patients.

Left Ventricular Diastolic Dysfunction and Diastolic Heart Failure in Preterm Infants Abstract Diastolic dysfunction is primarily an echocardiographic diagnosis. Its clinical counterpart is diastolic heart failure, where the heart has difficulty to fill at normal pressure and the patient develops signs of pulmonary edema. Although diastolic dysfunction is common in adults, limited information is available in preterm infants. The aim of this study is to explore left ventricular diastolic dysfunction and diastolic heart failure in preterm infants and describe clinical manifestations in this population. This is a retrospective observational study in preterm infants < 30 weeks’ gestation who received an echocardiography in the first 4 weeks after birth. Diastolic dysfunction was graded using a population-specific adapted version of the adult recommendations for the evaluation of left ventricular diastolic function by echocardiography. Left ventricular diastolic dysfunction was absent, indeterminate, and definite in 82%, 14%, and 4% of the 168 echocardiograms analyzed, and is associated with increased respiratory signs and respiratory deterioration at 48 h before echocardiogram. In seven infants, diastolic heart failure was diagnosed with both ultrasound and clinical signs. The cumulative risk of diastolic dysfunction increased with the increasing postnatal age and a patent ductus arteriosus. Evidence of left ventricular diastolic dysfunction on echocardiography is relatively common in preterm infants, while the left ventricular diastolic heart failure is less frequent. Prolonged exposure to volume load was the most common cause.

Orthostatic and Exercise Effects in Children Years After Kawasaki Disease Abstract The long-term orthostatic and/or exercise hemodynamic effects in children years after Kawasaki disease (KD) were studied using clinical data from the treadmill exercise test (TMET). Heart rate (HR) and blood pressures (BPs) recorded in TMET were compared between two age, gender, and body scale-matched groups of patients with and without a history of KD. The KD group included 60 patients (9.8 ± 2.7 years old) 6.6 ± 2.6 years after KD without coronary arterial aneurysm. The non-KD group included 60 children (10.2 ± 2.7 years old) with other diagnoses. The exercise tolerance in TMET was not statistically different between the two groups. The KD group had a faster HR on standing than the non-KD group by 8.6% (101.5 ± 12.2 vs. 93.5 ± 15.9 bpm, respectively; P < 0.01), suggesting weaker and/or retarded orthostatic vasoconstriction. The pulse pressure was largely augmented above the 4th stage beyond 160 mmHg in 10.6 versus 0% (5 vs. 0) of the KD and non-KD groups (P < 0.05), respectively, while HR and BPs were not significantly different through exercise stages between the two groups. The KD group also showed a faster HR recovery five minutes after exercise than the non-KD group, by 5.7% (108.0 ± 11.6 vs. 102.2 ± 14.2 bpm, respectively; P < 0.05). Our results might indicate long-term subclinical impacts on the vascular tonus of children years after the disease that have not been recognized in previous studies.

Personalised Warfarin Dosing in Children Post-cardiac Surgery Abstract Warfarin dosing is challenging due to a multitude of factors affecting its pharmacokinetics (PK) and pharmacodynamics (PD). A novel personalised dosing algorithm predicated on a warfarin PK/PD model and incorporating CYP2C9 and VKORC1 genotype information has been developed for children. The present prospective, observational study aimed to compare the model with conventional weight-based dosing. The study involved two groups of children post-cardiac surgery: Group 1 were warfarin naïve, in whom loading and maintenance doses were estimated using the model over a 6-month duration and compared to historical case-matched controls. Group 2 were already established on maintenance therapy and randomised into a crossover study comparing the model with conventional maintenance dosing, over a 12-month period. Five patients enrolled in Group 1. Compared to the control group, the median time to achieve the first therapeutic INR was longer (5 vs. 2 days), to stable anticoagulation was shorter (29.0 vs. 96.5 days), to over-anticoagulation was longer (15.0 vs. 4.0 days). In addition, median percentage of INRs within the target range (%ITR) and percentage of time in therapeutic range (%TTR) was higher; 70% versus 47.4% and 83.4% versus 62.3%, respectively. Group 2 included 26 patients. No significant differences in INR control were found between model and conventional dosing phases; mean %ITR was 68.82% versus 67.9% (p = 0.84) and mean %TTR was 85.47% versus 80.2% (p = 0.09), respectively. The results suggest model-based dosing can improve anticoagulation control, particularly when initiating and stabilising warfarin dosing. Larger studies are needed to confirm these findings.

Upcoming Events in Pediatric Cardiology

Long QT Syndrome: Genetics and Future Perspective Abstract Long QT syndrome (LQTS) is an inherited primary arrhythmia syndrome that may present with malignant arrhythmia and, rarely, risk of sudden death. The clinical symptoms include palpitations, syncope, and anoxic seizures secondary to ventricular arrhythmia, classically torsade de pointes. This predisposition to malignant arrhythmia is from a cardiac ion channelopathy that results in delayed repolarization of the cardiomyocyte action potential. The QT interval on the surface electrocardiogram is a summation of the individual cellular ventricular action potential durations, and hence is a surrogate marker of the abnormal cellular membrane repolarization. Severely affected phenotypes administered current standard of care therapies may not be fully protected from the occurrence of cardiac arrhythmias. There are 17 different subtypes of LQTS associated with monogenic mutations of 15 autosomal dominant genes. It is now possible to model the various LQTS phenotypes through the generation of patient-specific induced pluripotent stem cell-derived cardiomyocytes. RNA interference can silence or suppress the expression of mutant genes. Thus, RNA interference can be a potential therapeutic intervention that may be employed in LQTS to knock out mutant mRNAs which code for the defective proteins. CRISPR/Cas9 is a genome editing technology that offers great potential in elucidating gene function and a potential therapeutic strategy for monogenic disease. Further studies are required to determine whether CRISPR/Cas9 can be employed as an efficacious and safe rescue of the LQTS phenotype. Current progress has raised opportunities to generate in vitro human cardiomyocyte models for drug screening and to explore gene therapy through genome editing.

Insights into Arch Vessel Development in the Bovine Aortic Arch Abstract A bovine arch is the most common aortic arch variant, characterized by a common origin of the innominate artery and the left common carotid artery. Data have shown that children with bovine arch anatomy and coarctation are at a significantly higher risk of recoarctation following coarctation repair. This study aims to explain the higher coarctation rates, assess the branching of the arch vessels, understand their embryologic origins, and delineate the patterns of displacement of the arch vessels in bovine versus normal anatomy. This retrospective study reviewed the medical records of 178 infants ( < 1-year-old) who had a chest CT Angiogram (58) or CT (120) at our institution between 2007 and 2017. Multiplanar reconstruction software was used to obtain the best image plane to display the sinotubular junction, innominate artery, left common carotid artery, and left subclavian artery. We measured the distances between the branches as HV1, HV2, and HV3. All distances were standardized to body surface area and sinotubular junction diameter, which is a novel method. Bovine arches were found in 32.6% of patients. The total arch length of both arch anatomies was similar. HV3 is longer in bovine arches. HV1 + HV2 and HV2 + HV3 are longer in the normal arches than the bovine arches. The left subclavian artery moves proximally, and the innominate artery moves slightly distally to form the bovine arch and decreasing the clamping distance for coarctation repair. Aortic arch distances were similar when standardized to either sinotubular junction diameter and body surface area.

Differential Myocardial Mechanics in Volume and Pressure Loaded Right Ventricles Demonstrated by Cardiac Magnetic Resonance Abstract In patients with D-looped transposition of the great arteries (D-TGA) status post atrial switch operation, the systemic right ventricle (RV) shifts to predominantly circumferential (CS) rather than longitudinal strain (LS), which may represent adaptation or dysfunction. We aimed to evaluate myocardial mechanics in pressure loaded, volume-loaded, and normal RVs by cardiac magnetic resonance (CMR). Patients with D-TGA post atrial switch operation with CMR from 2008 to 2015 were matched 1:1 for age and RV ejection fraction (EF) with repaired tetralogy of Fallot (TOF) patients (volume-loaded RVs), and 1:1 for age with control patients. RV free wall LS and CS were measured using feature tracking software (TomTec, Unterscleissheim, Germany). A total of 32 D-TGA (median age 32 years, 56% male), 32 TOF, and 32 control patients were included. D-TGA patients had less dilatation than TOF patients (125 ± 35 ml/m2 vs. 149 ± 44 ml/m2, p = 0.02) and lower RVEF than controls (42.9 ± 7.7% vs. 56.3 ± 5.6%, p < 0.0001). RV LS was similar in D-TGA and TOF ( − 13.2 ± 4.5% vs. − 14.5 ± 5.9%, p = 0.32), both decreased compared to controls. However, CS in D-TGA was higher than controls ( − 14.1 ± 4.1% vs. − 11.4 ± 4.4%, p = 0.01), with a higher CS:LS ratio (1.2 ± 0.7 vs. 0.6 ± 0.3, p < 0.0001), while CS in TOF and controls did not differ. RVEF in D-TGA correlated closely with CS (r =  − 0.85, p < 0.0001) but not LS (r = 0.10, p = 0.58). I n conclusion, CMR can differentiate strain patterns in pressure- and volume-loaded RVs, with decreased LS in both conditions, while systemic RVs compensate with supra-normal CS. CS may be a more clinically relevant measure of RV function in this population.

Postnatal Cardiac Development and Regenerative Potential in Large Mammals Abstract The neonatal capacity for cardiac regeneration in mice is well studied and has been used to develop many potential strategies for adult cardiac regenerative repair following injury. However, translating these findings from rodents to designing regenerative therapeutics for adult human heart disease remains elusive. Large mammals including pigs, dogs, and sheep are widely used as animal models of humans in preclinical trials of new cardiac drugs and devices. However, very little is known about the fundamental cardiac cell biology and the timing of postnatal cardiac events that influence cardiomyocyte proliferation in these animals. There is emerging evidence that external physiological and environmental cues could be the key to understanding cardiomyocyte proliferative behavior. In this review, we survey available literature on postnatal development in various large mammal models to offer a perspective on the physiological and cellular characteristics that could be regulating cardiomyocyte proliferation. Similarities and differences between developmental milestones, cardiomyocyte maturational events, as well as environmental cues regulating cardiac development, are discussed for various large mammals, with a focus on postnatal cardiac regenerative potential and translatability to the human heart.

Propofol Formulation Affects Myocardial Function in Newborn Infants Abstract This study aimed to evaluate the effects of propofol in diluted and undiluted formulations on cardiac function in infants. Infants > 30 days received propofol sedation for central line insertion. Cases were divided into two groups: those who received undiluted 1% propofol (P1%); and those who received a diluted formulation (Pd) of equal volumes propofol 1% and 0.9% NaCl. Echocardiograms were performed pre (t0)-, immediately post (t1)-, and 1-h post (t2) propofol administration. Myocardial deformation was assessed with tissue Doppler imaging (TDI) analysis and peak longitudinal strain (LS). 18 cases were included: nine (50%) P1% and nine (50%) Pd. In the P1% group, TDI velocities and LS were significantly reduced at t1 and t2. In the Pd Group, only TDI velocities in the left ventricle were reduced at t1, but not at t2. Dilution of propofol may minimize myocardial dysfunction while maintaining adequate sedation in infants. Further comparative studies are needed to investigate the safety and efficacy of this approach.