Monesha Gupta-Malhotra

Atherosclerosis in Survivors of Kawasaki Disease

OBJECTIVES To test the hypothesis that long-term survivors of low-risk Kawasaki disease (KD) have ongoing vascular inflammation and dysfunction and a higher risk of accelerated atherosclerosis than healthy control subjects. STUDY DESIGN Twenty-eight patients with KD (7-20 years after acute illness) and 27 age-matched healthy control subjects were examined for medical and dietary history, serum markers of atherosclerotic risk and inflammation, carotid intimal-medial thickness (CIMT) with vascular ultrasound scanning and arterial stiffness with applanation tonometry. RESULTS Patients and control subjects were similar in age, sex, body mass index, waist-to-hip ratio, blood pressure, cigarette smoking, family history, diet, high-density lipoprotein cholesterol level, lipoprotein (a) level, homocysteine level, glucose level, insulin level, CIMT, arterial stiffness, C-reactive protein level, and inflammatory cytokine level. Levels of total cholesterol and apolipoprotein B were significantly higher in patients with KD than in control subjects. CONCLUSIONS There was no evidence of increased atherosclerosis. Small but significant differences in cholesterol and apolipoprotein B levels could suggest increased future risk for atherosclerosis and warrant further study.

Current perspectives on Kawasaki disease.

The etiology of Kawasaki disease (KD) remains unknown despite several years of dedicated research in this direction. Recently coronavirus infection and genetic polymorphisms have been implicated. Since first description of the disease there have been few changes in the diagnostic criteria except for newer recommendations of fever of at least 4 instead of 5 days duration. Recently, Echocardiography Criteria and Laboratory Criteria have been added to aid in the diagnosis of incomplete KD where all the historical diagnostic criteria are not present; this is now called the “incomplete form of KD” as opposed to “atypical form of KD”. The word “atypical” is reserved for unusual presentations of KD such as those with hemophagocytic syndrome or nerve palsy. The treatment of KD includes infusion of high dose immunoglobulin. Patients nonresponsive to immunoglobulin therapy are labeled as having “immunoglobulin resistant KD”. The treatment of immunoglobulin resistant KD can be challenging and new therapies that have tried with some success. Late outcomes after 4 decades of treating these patients have recently been published. There has been some concern about increased risk for premature atherosclerosis in patients with childhood KD who had coronary artery abnormalities.

Mortality After Total Cavopulmonary Connection in Children With the Down Syndrome

A total cavopulmonary connection (Fontan surgery) is rarely performed in a child with trisomy 21 (Down syndrome) for a univentricular heart, and the outcomes after surgery are not well defined, but the incidence of mortality has been reported to be higher. To determine the mortality rate and contributing factors after Fontan surgery in children with Down syndrome, mortality data after Fontan surgery from the Pediatric Cardiac Care Consortium Registry were evaluated. Among Fontan procedures (n = 2,853), all patients with Down syndrome (n = 17) were selected, of whom 13 had hemodynamic data available. Thirteen children without chromosomal aberrations were then selected as a control group, matched 1 to 1 for gender, age, weight, lesion, and type of Fontan procedure. The following variables were evaluated: pulmonary artery pressure and vascular resistance, weight, hemoglobin, degree of atrioventricular regurgitation, previous Glenn operation, fenestration, and length of stay in the hospital. In children with Down syndrome, mortality after the Glenn operation was 28%. Mortality after the Fontan operation was increased significantly (p = 0.001) in children with Down syndrome (35%) compared with those without Down syndrome (10%). Between patients with Down syndrome and controls, there were no significant differences in the perioperative parameters evaluated. Almost all mortality was in the early postoperative period in children with Down syndrome. The relative risk ratio of mortality was 2.5 (95% confidence interval 0.63 to 10). In conclusion, Down syndrome was found to be an independent parameter associated with a significantly higher risk for mortality in the early postoperative period after Fontan surgery.

Characteristics of Systemic Hypertension in Preterm Children

The prevalence of essential hypertension (EH) among preterm children is unknown. The authors evaluated consecutive children with a diagnosis of hypertension and prematurity (gestational age <37 weeks) in a tertiary pediatric hypertension clinic and identified 36 preterm hypertensive children. Among these preterm children, 23 were diagnosed in the neonatal intensive care unit (NICU; infantile) and 13 were diagnosed at an older age (childhood). When compared with patients with a childhood diagnosis, patients with an infantile diagnosis had a significantly lower gestational age, longer duration of hospitalization in the NICU, and a higher incidence of perinatal risk factors for hypertension. None with infantile diagnosis had EH, whereas 46% with childhood diagnosis had EH. Among premature children, systemic hypertension was either diagnosed in infancy or in childhood, with each age at diagnosis having unique risk factors and clinical course. Although 83% of preterm children had secondary hypertension, EH was diagnosed in 17% and was only seen in those diagnosed beyond infancy.

Prevalence of undiagnosed congenital cardiac defects in older children.

BACKGROUND Certain congenital cardiac defects may go undetected for several years due to lack of symptoms and signs. Our purpose was to determine the prevalence of such defects among children greater than one year of age. METHODS The study was performed on subjects diagnosed with systemic hypertension, aged from 1 to 19 years, with a mean of 12.4 years, in whom we performed echocardiography, using a standard protocol, to establish any end-organ damage or to reveal any congenital cardiac defects. RESULTS We found a congenital cardiac defect in 5 (3.5%) of the 143 children evaluated. Of these, 4 had not previously been detected, specifically Ebsteins malformation of the tricuspid valve, with moderate regurgitation, a coronary arterial anomaly, a bicuspid aortic valve, and prolapse of the mitral valve permitting regurgitation. In the other patient, we found a non-significant tiny muscular ventricular septal defect. CONCLUSIONS Our transthoracic echocardiographic investigation revealed previously unsuspected congenital cardiac defects in 4 of 143 older children, with 3 of these requiring further management by a paediatric cardiologist. A similar prevalence has also been reported in older children evaluated echocardiographically for other diseases such as insulin-resistance and leukemia. Hence, it is possible that the prevalence of congenitally malformed hearts is higher than previously reported. When clinically indicated, clinicians should more readily consider obtaining an echocardiogram to help in the identification of such malformations.

Cardiac troponin I after cardiopulmonary bypass in infants in comparison with older children.

OBJECTIVE At the present time, there is a trend towards performing open heart surgery at a younger age. Myocardium of infants has been thought to be more vulnerable to cardiopulmonary bypass in comparison with adults. For this study, we evaluated the degree of myocardial injury by measurement of cardiac troponin levels in infants in comparison with older children for similar surgeries. METHODS Serum was collected before bypass, after bypass, and daily after surgery and serum cardiac troponin I level (micrograms per litre). The demographic data, cardiac diagnoses, types of surgery performed, and peri-operative parameters were collected. RESULTS Of the 21 children enrolled consecutively, five were infants. Among the 21 patients, four patients had post-operative peak troponin values greater than 100 (three were infants) and all four patients survived and had normal left ventricular systolic function upon discharge echocardiogram. The five infants had peak troponin levels of 222.3, 202, 129, 26.7, and 82.3. The post-operative peak troponin levels were significantly higher in infants (mean 132.5 with a standard deviation of 81.6) than in the older children (mean 40.3 with a standard deviation of 33.4), although there was no significant difference in bypass time, bypass temperature, cross-clamp time, or the length of stay in the intensive care unit between the two age groups. CONCLUSIONS Higher troponin release is seen in infants in comparison with older children after bypass for similar surgeries. A troponin level greater than 100 after bypass does not necessarily predict death or a severe cardiovascular event in the very young.

Left Ventricular Hypertrophy Phenotype in Childhood-Onset Essential Hypertension

The aim of this study was to determine the risk factors associated with left ventricular (LV) hypertrophy (LVH) among 89 untreated children with primary hypertension. Clinic hypertension was confirmed by 24‐hour ambulatory blood pressure (BP) monitoring. LV mass (LVM) index was calculated as LVM (g)/height (m)2.7 and LVH was defined as LVM index >95th percentile. Children with (n=32) and without (n=57) LVH were compared. Both obesity and systolic BP were independently associated with LVH, with a higher contribution by body mass index. Obesity contributed significantly, with a nearly nine‐fold increased risk of LVH. There was evidence of effect modification by the presence or absence of obesity on the relationship between systolic BP and LVH, whereby the relationship existed mainly in nonobese rather than obese children. Hence, to achieve reversal of LVH, clinicians should take into account both BP control and weight management.

Deterioration of cutaneous microcirculatory status of Kawasaki disease

Kawasaki disease (KD) is associated with generalized vasculitis with a predilection for coronary artery leading to ectasia and aneurysm in some cases. The aim of this study was to noninvasively assess the cutaneous microcirculation and correlate it with the coronary artery diameter in these patients. Laser Doppler flowmetry and dynamic capillaroscopy were performed at the nailbeds to assess total cutaneous blood flow and microcirculation in children with KD, both in the afebrile phase (after the resolution of fever) and convalescent phases, in comparison to controls. The 100 subjects analyzed in this study included 64 patients with KD (33 in afebrile phase and 31 in convalescent phase) and 36 normal controls. In KD, the capillary morphology was abnormal when compared to controls, with a larger diameter of the arterial and venous limbs, a higher intercapillary distance and a decrease in the loop numbers. Significantly decreased capillary blood cell velocity was noted in afebrile phase but not in convalescent phase. In the afebrile phase, a decreased capillary blood cell velocity significantly correlated with an increased coronary artery diameter. In conclusion, KD patients, both in the afebrile and convalescent phases, exhibited morphologic alterations in the microcirculation when compared to the controls. The results indicate the potential role of dynamic capillaroscopy for the noninvasive survey of microcirculation abnormalities in patients with KD.

Myocardial Performance Index in Childhood Onset Essential Hypertension and White Coat Hypertension.

BACKGROUND As a global measure of ventricular systolic and diastolic function, the myocardial performance index (MPI) can be an early indicator of hypertensive cardiomyopathy in children with essential hypertension (EH). METHODS Children with untreated newly diagnosed EH and white coat hypertension (WCH) by a 24-hour ambulatory blood pressure monitoring (ABPM), both groups without any identifiable etiology for the hypertension, were enrolled for the study. Echocardiograms and vascular ultrasounds for carotid artery intimal medial thickness were performed on all children prior to therapy. Diastolic function (peak E and A velocities, E/A ratio, isovolumic relaxation time, and deceleration times) and MPI were evaluated by simultaneous transmitral and transaortic spectral Doppler flow velocities. Systolic function was evaluated by shortening fraction and ejection fraction. RESULTS A cohort of 66 children (24 with EH, 42 with WCH, males 61%, median age of 13 years, range 10-17 years) were enrolled in the study. The demographic, anthropometric, laboratory tests, vascular ultrasound, and conventional echocardiographic parameters were similar between the 2 groups. There was a very small difference in MPI between the EH and WCH children (0.28 SD: 0.07 vs. 0.31 SD: 0.08, P = 0.045). However, in EH children, MPI increased by 0.14 units for every 10 unit increase in mean ABPM systolic BP (95% confidence interval: 0.03-0.25). CONCLUSIONS We found the increasing MPI was associated with increasing 24-hour mean systolic BP in children with EH. Therefore, MPI may have utility as a single, quick, noninvasive method of detection and tracking of subclinical hypertensive heart disease.

Prenatal diagnosis of a mixed type of total anomalous pulmonary venous return.

Total anomalous pulmonary venous return (TAPVR) is a congenital heart malformation that can be diagnosed in the fetus by indirect indicators on an echocardiogram, such as inability to demonstrate the pulmonary veins returning to the left atrium by color Doppler, the presence of a chamber or the pulmonary venous confluence behind the left atrium, presence of a dilated superior vena cava, discrepancy between the right and left heart chambers and great arteries, and the demonstration of the ascending or descending common pulmonary vein or vertical vein. Some cases of TAPVR can be missed in utero, especially in a mixed type of TAPVR or a TAPVR associated with complex cardiac malformation. We report a case of a mixed TAPVR with complex cardiac malformation which was diagnosed in the fetal period by direct visualization of anomalous pulmonary venous drainage and was confirmed by postnatal echocardiogram and cardiac magnetic resonance imaging.