Patterns of Electrocardiographic Abnormalities in Children with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM.

Importance of genetic testing in unexplained cardiac arrest.

AIMS: Genetic testing is recommended in specific inherited heart diseases but its role remains unclear and it is not currently recommended in unexplained cardiac arrest (UCA). We sought to assess the yield and clinical utility of genetic testing in UCA using whole-exome sequencing (WES). METHODS AND RESULTS: Survivors of UCA requiring external defibrillation were included from the Cardiac Arrest Survivor with Preserved Ejection fraction Registry. Whole-exome sequencing was performed, followed by assessment of rare variants in previously reported cardiovascular disease genes. A total of 228 UCA survivors (mean age at arrest 39 ± 13 years) were included. The majority were males (66%) and of European ancestry (81%). Following advanced clinical testing at baseline, the likely aetiology of cardiac arrest was determined in 21/228 (9%) cases. Whole-exome sequencing identified a pathogenic or likely pathogenic (P/LP) variant in 23/228 (10%) of UCA survivors overall, increasing the proportion of 'explained' cases from 9% only following phenotyping to 18% when combining phenotyping with WES. Notably, 13 (57%) of the 23 P/LP variants identified were located in genes associated with cardiomyopathy, in the absence of a diagnosis of cardiomyopathy at the time of arrest. CONCLUSIONS: Genetic testing identifies a disease-causing variant in 10% of apparent UCA survivors. The majority of disease-causing variants was located in cardiomyopathy-associated genes, highlighting the arrhythmogenic potential of such variants in the absence of an overt cardiomyopathy diagnosis. The present study supports the use of genetic testing including assessment of arrhythmia and cardiomyopathy genes in survivors of UCA.

Mutation to ispA Produces Stable Small-Colony Variants of Pseudomonas aeruginosa That Have Enhanced Aminoglycoside Resistance.

Pseudomonas aeruginosa is a major pathogen in burn wound infections. We present one of the first reports of small-colony variant (SCV) emergence of P. aeruginosa, taken from a patient under aminoglycosides for a persistent burn wound infection. We confirm the causative role of a single ispA mutation in SCV emergence and increased aminoglycoside resistance. IspA is involved in the synthesis of ubiquinone, providing a possible link between electron transport and SCV formation in P. aeruginosa.

Health management of patients with COVID-19: is there a room for hydrotherapeutic approaches?

With highly variable types of coronavirus disease 2019 (COVID-19) symptoms in both severity and duration, there is today an important need for early, individualized, and multidisciplinary strategies of rehabilitation. Some patients present persistent affections of the respiratory function, digestive system, cardiovascular function, locomotor system, mental health, sleep, nervous system, immune system, taste, smell, metabolism, inflammation, and skin. In this context, we highlight here that hydrothermal centers should be considered today as medically and economically relevant alternatives to face the urgent need for interventions among COVID-19 patients. We raise the potential benefits of hydrotherapy programs already existing which combine alternative medicine with respiratory care, physical activity, nutritional advice, psychological support, and physiotherapy, in relaxing environments and under medical supervision. Beyond the virtues of thermal waters, many studies reported medical benefits of natural mineral waters through compressing, buoyancy, resistance, temperature changes, hydrostatic pressure, inhalations, or drinking. Thermal institutions might offer individualized follow-up helping to unclog hospitals while ensuring the continuity of health care for the different clinical manifestations of COVID-19 in both post-acute and chronic COVID-19 patients. Our present review underlines the need to further explore the medical effectiveness, clinical and territorial feasibility, and medico-economic impacts of the implementation of post-COVID-19 patient management in hydrotherapeutic establishments.

Short-coupled ventricular fibrillation represents a distinct phenotype among latent causes of unexplained cardiac arrest: a report from the CASPER registry.

AIMS: The term idiopathic ventricular fibrillation (IVF) describes survivors of unexplained cardiac arrest (UCA) without a specific diagnosis after clinical and genetic testing. Previous reports have described a subset of IVF individuals with ventricular arrhythmia initiated by short-coupled trigger premature ventricular contractions (PVCs) for which the term short-coupled ventricular fibrillation (SCVF) has been proposed. The aim of this article is to establish the phenotype and frequency of SCVF in a large cohort of UCA survivors. METHODS AND RESULTS: We performed a multicentre study including consecutive UCA survivors from the CASPER registry. Short-coupled ventricular fibrillation was defined as otherwise unexplained ventricular fibrillation initiated by a trigger PVC with a coupling interval of <350 ms. Among 364 UCA survivors, 24/364 (6.6%) met diagnostic criteria for SCVF. The diagnosis of SCVF was obtained in 19/24 (79%) individuals by documented ventricular fibrillation during follow-up. Ventricular arrhythmia was initiated by a mean PVC coupling interval of 274 ± 32 ms. Electrical storm occurred in 21% of SCVF probands but not in any UCA proband (P < 0.001). The median time to recurrent ventricular arrhythmia in SCVF was 31 months. Recurrent ventricular fibrillation resulted in quinidine administration in 12/24 SCVF (50%) with excellent arrhythmia control. CONCLUSION: Short-coupled ventricular fibrillation is a distinct primary arrhythmia syndrome accounting for at least 6.6% of UCA. As documentation of ventricular fibrillation onset is necessary for the diagnosis, most cases are diagnosed at the time of recurrent arrhythmia, thus the true prevalence of SCVF remains still unknown. Quinidine is effective in SCVF and should be considered as first-line treatment for patients with recurrent episodes.

Shock to the Heart: Psychosocial Implications and Applications of Sudden Cardiac Death in the Young.

PURPOSE OF REVIEW: Although rare, sudden cardiac death (SCD) in the young is a tragic event, having a dramatic impact upon all involved. The psychosocial burden associated with SCD can leave friends, families, and entire communities bereft. With only limited evidence to describe the volatile emotional reactions associated with a young SCD, there is an urgent need for care providers to better understand the psychological complexities and impacts faced by both at-risk individuals and those directly affected by these tragic events. RECENT FINDINGS: Current knowledge of the psychosocial implications associated with SCD in the young has recently generated interest in the cardiovascular community, with the goal of addressing prevention strategies (screening), family bereavement, and the psychological impact of at-risk or surviving individuals. With the emergence of novel strategies aimed at reducing the public health impact of SCD in the young, further discussion regarding the psychosocial impact of SCD, encompassing prevention, survivorship, and the downstream communal effects of a young death is required. Support systems and intervention could assist in the management of the associated psychosocial burden, yet there is a lack of clinical guidelines to direct this form of care. There is an important need for multidisciplinary collaboration across subspecialties to provide support to grieving individuals and manage patient well-being throughout the screening process for SCD. This collaborative approach requires the integration of cardiovascular and psychological expertise where relevant.

Echocardiographic Parameters During and Beyond Onset of Kawasaki Disease Correlate with Onset Serum N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP).

The N-terminal proBNP (NT-proBNP), produced by cardiomyocytes, has several reported utilities and associations in acute Kawasaki disease (KD). The objective of this study is to examine the relationship between serum values of NT-proBNP at time of KD diagnosis with cardiac systolic, diastolic function and electrocardiographic changes, at onset of the disease and during the first year of follow-up. KD was diagnosed in 127 children between March 2007 and July 2014, mean diagnostic age 3.5 ± 2.9 years. Coronary artery maximum z score was 2.6 ± 2.8 (range - 0.6 to + 18.9), with giant aneurysm in 5/122 (4.1%). Age-adjusted NT-proBNP was 2.6 ± 1.6 z score, 78/122 (63.9%) > 2.0. There was a crescendo correlation between onset NT-proBNP z score and C-Reactive protein (CRP) serum levels (slope + 0.49, p < 0.001). There was a crescendo correlation between NT-proBNP z score and indexed left ventricular (LV) mass (slope + 1.86, p = 0.02), LV diastolic function parameter E/e' ratio (slope + 0.31, p = 0.04) and a decrescendo correlation with age-adjusted LV shortening fraction (SF) (- 0.63, p = 0.02). Lower SF z score, higher left ventricular mass index and E/e' ratio were associated with higher NT-proBNP z score, but without correlation with CRP levels. Within 2-3 months from the onset of the disease, there was a resolution of the systolic dysfunction. Electrocardiographic parameter changes were associated with decreased LV shortening fraction but not with NT-proBNP. KD patients with elevated NT-proBNP at onset have sub-clinical myocardial involvement and might benefit from follow-up and continued evaluation, even in the absence of coronary artery involvement.

Impact of Obesity on Left Ventricular Thickness in Children with Hypertrophic Cardiomyopathy.

Obesity is associated with additional left ventricular hypertrophy (LVH) in adults with hypertrophic cardiomyopathy (HCM). It is not known whether obesity can lead to further LVH in children with HCM. Echocardiographic LV dimensions were determined in 504 children with HCM. Measurements of interventricular septal thickness (IVST) and posterior wall thickness (PWT), and patients' weight and height were recorded. Obesity was defined as a body mass index (BMI) ≥ 99th percentile for age and sex. IVST data was available for 498 and PWT data for 484 patients. Patient age ranged from 2 to 20 years (mean ± SD, 12.5 ± 3.9) and 340 (68%) were males. Overall, patient BMI ranged from 7 to 50 (22.7 ± 6.1). Obesity (BMI 18-50, mean 29.1) was present in 140 children aged 2-19.6 (11.3 ± 4.1). The overall mean IVST was 20.5 ± 9.6 mm and the overall mean PWT was 11.0 ± 8.4 mm. The mean IVST in the obese patients was 21.6 ± 10.0 mm and mean PWT was 13.3 ± 14.7 mm. The mean IVST in the non-obese patients was 20.1 ± 9.5 mm and mean PWT was 10.4 ± 4.3 mm. Obesity was not significantly associated with IVST (p = 0.12), but was associated with increased PWT (0.0011). Obesity is associated with increased PWT but not IVST in children with HCM. Whether obesity and its impact on LVH influences clinical outcomes in children with HCM needs to be studied.

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center.

The objective of this study was to investigate the population pharmacokinetics (PK) of amoxicillin in ICU burn patients and the optimal dosage regimens. This was a prospective study involving 21 consecutive burn patients receiving amoxicillin. PK data were analyzed using nonlinear mixed-effects modeling. Monte-Carlo simulations assessed the influence of various amoxicillin dosage regimens with identified covariates on the probability to achieve a target (PTA) value of time during which free amoxicillin concentrations in plasma exceeded the MIC (fT>MIC). A two-compartment model best described the data. Creatinine clearance (CLCR) and body weight (BW) influenced amoxicillin CL and central volume of distribution (V1), respectively. The median CLCR (Cockcroft-Gault formula) was high (128 ml/min), with 25% of patients having CLCRs of >150 ml/min. The CL, V1, and half-life (t1/2) values at steady state for a patient with a CLCR of 110 ml/min and BW of 70 kg were 13.6 liters/h, 9.7 liters, and 0.8 h, respectively. Simulations showed that a target fT>MIC of ≥50% was achieved (PTA > 90%) with standard amoxicillin dosage regimens (1 to 2 g every 6 to 8 h [q6-8h]) when the MIC was low (<1 mg/liter). However, increased dosages of up to 2 g/4 h were necessary in patients with augmented CLRs or higher MICs. Prolonging amoxicillin infusion from 30 min to 2 h had a favorable effect on target attainment. In conclusion, this population analysis shows an increased amoxicillin CL and substantial CL PK variability in burn patients compared to literature data with nonburn patients. Situations of augmented CLCR and/or high bacterial MIC target values may require dosage increases and longer infusion durations. (This study has been registered at ClinicalTrials.gov under identifier NCT01965340.).

The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry.

Aims: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. Methods and results: This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. Conclusion: This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events.

N-terminal pro-B-type natriuretic peptide diagnostic algorithm versus American Heart Association algorithm for Kawasaki disease.

BACKGROUND: Diagnosis of Kawasaki disease (KD) can be challenging in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete. We recently proposed serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunctive diagnostic test. METHODS: We retrospectively tested a new algorithm to help KD diagnosis based on NT-proBNP, coronary artery dilation (CAD) at onset, and abnormal serum albumin or C-reactive protein (CRP). The goal was to assess the performance of the algorithm and compare its performance with that of the 2004 American Heart Association (AHA)/American Academy of Pediatrics (AAP) algorithm. RESULTS: The algorithm was tested on 124 KD patients with NT-proBNP measured on admission at the present institutions between 2007 and 2013. Age at diagnosis was 3.4 ± 3.0 years, with a median of five diagnostic criteria; and 55 of the 124 patients (44%) had incomplete KD. CA complications occurred in 64 (52%), with aneurysm in 14 (11%). Using this algorithm, 120/124 (97%) were to be treated, based on high NT-proBNP alone for 79 (64%); on onset CAD for 14 (11%); and on high CRP or low albumin for 27 (22%). Using the AHA/AAP algorithm, 22/47 (47%) of the eligible patients with incomplete KD would not have been referred for treatment, compared with 3/55 (5%) with the NT-proBNP algorithm (P < 0.001). CONCLUSION: This NT-proBNP-based algorithm is efficient to identify and treat patients with KD, including those with incomplete KD. This study paves the way for a prospective validation trial of the algorithm.

Atrial Septal Defect Closure with Occlutech® ASD Fenestrated Device in a Child with Severe Pulmonary Hypertension.

We report a 5-year-old patient with severe pulmonary hypertension and a large secundum atrial septal defect who benefited from a percutaneous closure of the defect with an Occlutech® custom-made fenestrated device. Whereas the closure is technically identical to standard atrial defect closure, the immediate and midterm beneficial results are presented.

Importance of anatomical dominance in the evaluation of coronary dilatation in Kawasaki disease.

Introduction In Kawasaki disease, although coronary dilatation is attributed to vasculitis, the effect of myocardial inflammation is underestimated. Coronary dilatations are determined by Z-scores, which do not take into account dominance. The aim of the present study was to describe the impact of coronary dominance on dilatation in Kawasaki disease. METHODS: We performed a retrospective analysis of coronary dilatations according to angiography categorisation of dominance. RESULTS: Of 28 patients (2.6 [0.2-10.1] years), right dominance was present in 15 patients and left in 13. Early dilatation was present in all patients, of whom 11 were ipsilateral to the dominant segment and 17 contralateral. Ipsilateral dilatations were present at diagnosis (9/11 versus 6/17, p=0.02) compared with contralateral dilatations, which developed 2 weeks after diagnosis (9/11 versus 16/17, p=0.29). Coronary artery Z-scores of patients with contralateral dilatation increased at 2 weeks, before returning to baseline values (2.0±2.2 at diagnosis, 4.1±1.8 at 2 weeks, 1.8±1.2 at 3-6 months, p=0.001), compared with patients with ipsilateral dilatation in whom Z-scores were maximal at diagnosis and remained stable (3.0±0.9, 2.7±1.1 and 2.6±1.5, respectively, p=0.13). Dominant coronary artery Z-scores were higher compared with non-dominant segments at diagnosis (3.0±0.9 versus 1.0±0.8, p<0.001) and at late follow-up (2.6±1.5 versus 0.4±1.4, p=0.002) in patients with ipsilateral dilatation. CONCLUSION: Progression of coronary dilatation after diagnosis may be a sign of dilatation secondary to vasculitis, as opposed to regression of Z-scores in ipsilateral dilatations, probably related to physiological vasodilatation in response to carditis. This needs to be validated in larger studies against vasculitic and myocardial inflammatory markers.

Pulse oximetry screening in newborns to enhance detection of critical congenital heart disease.

Pulse oximetry screening is safe, noninvasive, easy to perform and proven to enhance detection of critical congenital heart disease in newborns. However, this test has yet to be adopted as routine practice in Canada. The present practice point highlights essential details and recommendations for screening, which research has shown to be highly specific, with low false-positive rates. Optimal screening for critical congenital heart disease should include prenatal ultrasound, physical examination and pulse oximetry screening. Screening should be performed between 24 hours and 36 hours postbirth, using the infant's right hand and either foot to minimize false-positive results. Newborns with abnormal results should undergo a thorough evaluation by the most responsible health care provider. When a cardiac diagnosis cannot be excluded, referral to a paediatric cardiologist for consultation and echocardiogram is advised.

Coronary Artery Dilatation in Viral Myocarditis Mimics Coronary Artery Findings in Kawasaki Disease.

Coronary artery (CA) dilatations are typical to Kawasaki disease (KD) in the pediatric population. CA involvement is a useful feature to help establish the diagnosis of KD. Since myocarditis is omnipresent in the acute phase of KD, we sought to investigate whether viral myocarditis may cause CA dilatation. This retrospective study reviewed 14 consecutive patients diagnosed with acute myocarditis at CHU Sainte-Justine, Montreal. KD diagnosis was excluded for all patients. All echocardiography studies were reviewed by an independent experienced echocardiographer for CA size and myocardial function parameters. CA involvement was classified under three categories: definite dilatation (Z-score ≥2.5 in one or more CA), occult dilatation (Z-score variation ≥2 points for the same CA on two different echocardiograms, but maximum Z-score always <2.5), and no dilatation otherwise. Demographics, laboratory values, microbial etiology testing, and diagnostic studies were collected from medical records. Mean age at presentation was 1.67 ± 3.22 years, where 11/14 (78 %) presented with acute and three with subacute myocarditis. Five (36 %) patients had normal CA measurements, six (43 %) had occult dilatation, and three (21 %) had definite dilatation. Maximal CA Z-score was within the first 8 days of presentation. Patients with viral myocarditis can present CA dilatation during the acute phase of the illness. This finding should be taken into account when KD diagnosis is being based on the CA involvement as the two illnesses may present with similar features.

Aortic dilatation in patients with Turner's syndrome without structural cardiac anomaly.

INTRODUCTION: Dilatation of the ascending aorta is described in Turner's syndrome with variable prevalence (6.8-32%). Reported series typically include patients with associated cardiac anomalies. OBJECTIVE: To characterise the prevalence, age of onset, and the progress of dilatation of the ascending aorta in Turner's syndrome patients free of structural cardiac anomalies. Potential risk factors such as karyotype and growth hormone therapy were analysed for correlation with aortic dilatation. METHODS: We carried out a retrospective study with data collected from medical records and echocardiography studies. Patients with Tuner's syndrome followed-up between 1992 and 2010 with at least two echocardiography studies were eligible. Patients with previous cardiac surgery or under anti-hypertensive medication were excluded. Ascending aorta diameter measurements were adjusted for body surface area, and dilatation was defined as Z-score>2. RESULTS: The study population consisted of 44 patients, aged 11.9±7.4 years at the first echocardiogram and 17.9±7.3 years at the last follow-up, with a follow-up duration of 6.0±3.7 years. A total of 13 (29.5%) patients exhibited aortic dilatation during follow-up, suggesting an actuarial estimate of the freedom from aortic dilatation dropping from 86 to 70% and then to 37% at 10, 20, and 30 years of age, respectively. There was no statistically significant impact of karyotype or growth hormone therapy on aortic Z-score progression. CONCLUSION: The prevalence of dilatation of the ascending aorta in Turner's syndrome patients free of structural aortic anomalies is comparable with published data with associated lesions. Growth hormone therapy and karyotype had no significant impact; however, longitudinal follow-up is warranted.

Cardiovascular Response to Exercise Testing in Children and Adolescents Late After Kawasaki Disease According to Coronary Condition Upon Onset.

Multiple cardiovascular sequelae have been reported late after Kawasaki disease (KD), especially in patients with coronary artery lesions. In this perspective, we hypothesized that exercise response was altered after KD in patients with coronary aneurysms (CAA-KD) compared to those without history of coronary aneurysms (NS-KD). This study is a post hoc analysis of exercise data from an international multicenter trial. A group of 133 CAA-KD subjects was compared to a group of 117 NS-KD subjects. Subjects underwent a Bruce treadmill test followed to maximal exertion. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were assessed at each stage of the test including recovery. Myocardial perfusion was evaluated by stress and rest Tc-99m sestamibi SPECT imaging. Endurance time was similar between NS-KD and CAA-KD (11.3 ± 2.6 vs. 11.0 ± 2.6 min; p = 0.343). HR, SBP, and DBP responses to exercise were similar between groups (p = 0.075-0.942). Myocardial perfusion defects were present in 16.5 % CAA-KD versus 22.2 % NS-KD (p = 0.255). Analysis based on myocardial perfusion status identified a lower heart rate at 1 min into recovery as well as lower DBP at 1 and 5 min into recovery in patients with abnormal SPECT imaging (p = 0.017-0.042). Compared to patients without CA involvement, the presence of coronary aneurysms at the subacute phase of KD does not induce a differential effect on exercise parameters. In contrast, exercise-induced myocardial perfusion defect late after the onset of KD correlates with abnormal recovery parameters.

Ascending Aorta Elastography After Kawasaki Disease Compared to Systemic Hypertension.

Kawasaki disease (KD) is a systemic vasculitis, classically affecting large- and medium-size arteries. The coronary arteries draw most of the clinical attention, whereas few studies have taken interest in the ascending aorta. Using a proprietary imaging-based mechanical biomarker (ImBioMark), we sought to determine aortic stiffness in KD compared to systemic hypertension (HTN) and healthy children. We evaluated parasternal long-axis views focused on the ascending aorta in 20 controls, 12 KD, and 8 HTN as a comparative clinical model of vascular stiffness. We calculated systolic and diastolic aortic wall strain with ImBioMark. Strain was tested for normality against height, systolic, and diastolic blood pressure in normal subjects. Strain from KD and HTN was normalized (Z score) accordingly. Z score comparisons were performed using nonparametric statistics. Age was similar between KD and HTN (9.1 ± 5.3 and 9.9 ± 5.3 years old; p = NS). Systolic and diastolic strain values were normally distributed against height, systolic blood pressure, and diastolic blood pressure in healthy subjects. HTN subjects had abnormal systolic and diastolic strain values (p < 0.0001). Whereas KD subjects had normal diastolic strain, systolic strain was significantly lower (p < 0.001), and systolic strain was intermediate between controls and HTN. There were no significant differences in aortic strain among KD, however, according to the presence of coronary artery aneurysms. Despite normal blood pressure, the ascending aorta in KD exhibits reduced strain during systole. This may reflect in situ rigidity of the aorta. The normal diastolic strain in KD may, in contrast, reflect normal peripheral vascular resistance.

Timing of Dynamic NT-proBNP and hs-cTnT Response to Exercise Challenge in Asymptomatic Children with Moderate Aortic Valve Regurgitation or Moderate Aortic Valve Stenosis.

Patients with congenital aortic valve stenosis (AVS) can remain asymptomatic but may develop progressive and often underestimated exercise intolerance. The risk of increased left ventricular (LV) wall stress, irreversible myocardial fibrosis and sudden death in untreated patients warrants earlier intervention. The timing for curative therapy for severe AVS is clear, but optimal timing for moderate stenosis (modAS) is unknown. AVS often coexists with aortic regurgitation, which adds a volume overload to an already pressure-overloaded LV, adding an additional challenge to the estimation of disease severity. We investigated the possible value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) upon treadmill exercise challenge in children with asymptomatic modAS versus moderate regurgitation (modAR). The aim was to determine optimal timing of peak biochemical response. Blood samples were obtained at rest, and then at 20, 40 and 60 min after peak exercise comparing modAS and modAR to healthy controls. Exercise performance was equivalent in all groups, with no difference for biomarker levels at rest. The increase in NT-proBNP was significant in modAR at 40 min (99.2 ± 48.6 ng/L; p = 0.04) and 60 min into recovery (100.0 ± 53.7 ng/L; p = 0.01), but not in modAS. The increase in hs-cTnT was significant only at 60 min into recovery for modAS and modAR. NT-proBNP and hs-cTnT following exercise challenge are possible discriminant biomarkers of modAR from modAS and controls at 60 min into recovery despite comparable exercise performance. This offers a promising avenue for future stratification of aortic valve disease and optimal timing of intervention.

N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement.

BACKGROUND: We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease. OBJECTIVES: We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin. METHODS: We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated. RESULTS: There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1). CONCLUSION: Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.