Non-invasive assessment of aortic stiffness and blood pressure in young Turner syndrome patients.

Background Females with Turner syndrome (TS) carry an elevated risk of aortic dissection. The objective of the study was to assess the biophysical properties of the aorta and ambulatory blood pressure (BP) in females with TS and compare these findings to those in healthy female age-matched controls. Methods This was a prospective cohort study including subjects aged 8-25 years. Utilizing two-dimensional (2D) echocardiography and Doppler, proximal aortic dimensions were measured and biophysical properties of the aorta were calculated including pulse wave velocity (PWV), arterial pressure-strain elastic modulus and stiffness index. Resting BP was measured and ambulatory blood pressure monitoring (ABPM) was performed. Results Of 23 TS patients and 46 controls (median age 16.3 years), aortic annulus, sinus of Valsalva and sinotubular (ST) junction diameters, as well as left ventricular (LV) mass, were significantly greater in TS patients compared with controls when scaled for height2.7, but not for body surface area (BSA), although ascending aorta diameter was greater when scaled for both. Median PWV was faster in TS patients compared to controls (451 vs. 360 cm/s) while arterial pressure-strain elastic modulus and stiffness index were similar. Resting BP was abnormal in seven out of 22 patients and ABPM was abnormal in 16 out of 21 patients. Conclusions Young patients with TS had dilated proximal aortas when scaled for height2.7 and stiffer aortas when compared with healthy female age-matched controls. Moreover, resting BP underdiagnosed pre-hypertension and hypertension compared to ABPM. These findings are consistent with the presence of a primary aortopathy in TS.

Echocardiographic Assessment of Ventricular Function During Exercise in Adolescent Female Patients With Anorexia Nervosa.

BACKGROUND: Patients with anorexia nervosa (AN) have altered physiologic responses to exercise. The aim of this study was to investigate exercise capacity and ventricular function during exercise in adolescent patients with AN. METHODS: Sixty-six adolescent female patients with AN and 21 adolescent female control subjects who exercised to volitional fatigue on a semisupine ergometer, using an incremental step protocol of 20 W every 3 min, were retrospectively studied. Heart rate, blood pressure, and echocardiographic Doppler indices were measured at rest and during each stage of exercise. Fractional shortening, rate-corrected mean velocity of circumferential fiber shortening, stress at peak systole, cardiac output, and cardiac index were calculated. Minute ventilation, oxygen consumption, carbon dioxide production, and respiratory exchange ratio were measured using open-circuit spirometry. RESULTS: Patients with AN had significantly lower body mass index (16.7 vs 19.7 kg/m2, P < .001), total work (1,126 vs 1,914 J/kg, P < .001), and test duration (13.8 vs 20.8 min, P < .001) compared with control subjects. Peak minute ventilation, oxygen consumption, and carbon dioxide production were significantly decreased in patients with AN. Heart rate, systolic blood pressure, cardiac index, fractional shortening, and rate-corrected mean velocity of circumferential fiber shortening demonstrated similar patterns of increase with progressive exercise between groups but were decreased at peak exercise in patients with AN. Body mass index percentile, age, peak oxygen consumption, and peak cardiac output were independently associated with exercise duration. CONCLUSIONS: Adolescent patients with AN have reduced exercise capacity and peak cardiovascular indices compared with control subjects but normal patterns of cardiovascular response during progressive exercise. Systolic ventricular function is maintained during exercise in adolescents with AN.

Doppler Echocardiography Assessment of Aortic Stiffness in Female Adolescents with Anorexia Nervosa.

BACKGROUND: Anorexia nervosa (AN) is associated with abnormalities in biomarkers of cardiovascular risk. Arterial stiffness, as measured by pulse-wave velocity (PWV), is also a risk factor for cardiovascular disease. The aims of this study were to determine the stiffness of the aorta in female adolescents with AN and to determine if either the severity or the type of AN was associated with PWV. METHODS: This was a retrospective case-control study. Adolescent patients with a clinical diagnosis of AN were included. Aortic diameter and pulse-wave transit time over a portion of the thoracic aorta were measured using Doppler echocardiography, and PWV was calculated. RESULTS: There were 94 female patients with AN and 60 adolescent female control subjects. There was no significant difference in age between patients with AN and control subjects (15.5 ± 1.7 vs 15.1 ± 2.6 years, P = .220). Body mass index (16.0 ± 2.4 vs 19.7 ± 2.7 kg/m2, P < .001) and body mass index percentile (9.4 ± 15.6 vs 45.5 ± 26.2, P < .001) were significantly lower for patients with AN than control subjects. PWV (443 ± 106 vs 383 ± 77 cm/sec, P < .001) was significantly higher in patients with AN than control subjects. Similar differences from control subjects were found in patients with AN with both lower and higher body mass index percentiles and also in patients with AN with the restrictive or the binge-purge subtype. CONCLUSIONS: Female adolescents with AN have increased aortic stiffness compared with control subjects. This study suggests that patients with AN may be at increased risk for future cardiovascular disease. Future studies are required to determine the reversibility of these changes with weight restoration.

Genetic Insurance Discrimination in Sudden Arrhythmia Death Syndromes: Empirical Evidence From a Cross-Sectional Survey in North America.

BACKGROUND: There is virtually no information assessing the insurability of families affected with Sudden Arrhythmia Death Syndromes (SADS) for the determination of the nonclinical implications of genetic screening. It is important to identify the barriers and challenges faced by families as a result of genetic screening for SADS to enable equitable access to insurance coverage. METHODS AND RESULTS: To explore the insurance coverage experiences of SADS-affected families, we administered a cross-sectional online survey across North America from April 28, 2012 to November 13, 2013. Participants included individuals with a SADS diagnosis and their relatives who have applied for insurance (health, life, travel, and disability) or have existing insurance coverage. Of 202 participants, 92% had a SADS diagnosis (92%) as either a proband (50%) or an affected relative (42%); 8% of participants were unaffected family members of a proband; and genetic confirmation was reported by 73%. Of the 54% of SADS respondents who applied for insurance, 60% were rejected by insurers. The preexisting SADS diagnosis was the major reason reported for rejection (57%). Most respondents (80%) had insurance coverage through a spouse/parent plan at the time of diagnosis; 14% experienced a subsequent negative effect on coverage. Thirty-nine percent of affected SADS respondents reported an increase in insurance premium rates. CONCLUSIONS: Increased genetic testing has negatively impacted insurability for SADS patients and affected family members. The challenges in obtaining life and health insurance are mainly because of the preexisting condition, even in the presence of protective laws in the United States.

Assessment of Liver Stiffness in Pediatric Fontan Patients Using Transient Elastography.

Background. Hepatic fibrosis is a potential complication following Fontan surgery and heralds long-term risk for cirrhosis. Transient elastography (TE) is a rapid, noninvasive method to assess liver fibrosis by measuring liver stiffness. Objectives. To compare liver stiffness and liver biochemistries in pediatric Fontan patients with age- and sex-matched controls and to determine patients' acceptance of TE. Methods. Patients were recruited from British Columbia Children's Hospital. Twenty-two Fontan patients (15 males) were identified. Demographic information and cardiac data were collected. TE was measured using size-appropriate probes. Results. The median age of the Fontan cohort was 13.7 (5.9-16.8) years. Time from Fontan surgery to TE was 9.6 (1.0-12.9) years. The median Fontan circuit pressure was 13 (11-14) mmHg. TE values were higher in Fontan patients versus controls (18.6 versus 4.7 kPa, p < 0.001). There was no association between TE values and patient age (r = 0.41, p = 0.058), time since Fontan surgery (r = 0.40, p = 0.062), or median Fontan circuit pressure (CVP) (r = 0.35, p = 0.111). Patients found TE to be nonpainful, convenient, and safe. Conclusions. TE is feasible to assess liver stiffness in children following Fontan surgery. Pediatric Fontan patients have markedly elevated liver stiffness values. TE may have important utility in liver care follow-up of pediatric Fontan patients.

Noninvasive Assessment of Vascular Function in Postoperative Cardiovascular Disease (Coarctation of the Aorta, Tetralogy of Fallot, and Transposition of the Great Arteries).

Using noninvasive techniques, we sought to assess arterial stiffness, impedance, hydraulic power, and efficiency in children with postoperative tetralogy of Fallot (TOF), coarctation of the aorta (COA), and transposition of the great arteries (TGAs). Results were compared with those of healthy peers. Fifty-five children with repaired congenital heart disease (24 TOFs, 20 COAs, and 11 TGAs) were compared with 55 age-matched control subjects (CTRL). Echocardiographic Doppler imaging and carotid artery applanation tonometry were preformed to measure aortic flow, dimensions, and calculate pulse wave velocity, vascular impedance and arterial stiffness indexes, hydraulic power (mean and total), and hydraulic efficiency (HE) which were calculated using standard fluid dynamics equations. All congenital heart disease subgroups had higher pulse wave velocity than CTRL. Only the COA group had higher characteristic impedance. Mean power was higher in TGA than in CTRL and TOF, and total power was higher in TGA than in CTRL and TOF. Hydraulic efficiency was higher in TOF than in COA and TGA. In conclusion, children with TOF, COA, and TGA have stiffer aortas than CTRL. These changes may be related to intrinsic aortic abnormalities, altered integrity of the aorta due to surgical repair, and/or acquired postsurgery. These patients may be at increased long-term cardiovascular risk, and long-term follow-up is important for monitoring and assessment of efforts to reduce risk.

Noninvasive assessment of vascular function and hydraulic power and efficiency in pediatric Fontan patients.

BACKGROUND: Invasive studies have shown that children with Fontan palliation have abnormal arterial stiffness, impedance, and hydraulic power and efficiency. The aim of this study was to assess these indexes noninvasively in a cohort of children with Fontan circulation using Doppler echocardiography and compare their results with those of healthy peers. METHODS: This was a case-control study of 22 Fontan patients and 31 healthy control children. Using standard two-dimensional, M-mode, and Doppler echocardiographic imaging and carotid artery applanation tonometry, aortic flows, dimensions, and pulse-wave velocity were measured, and vascular impedance and arterial stiffness were calculated. Hydraulic power and efficiency were calculated from standard fluid dynamics formulae. RESULTS: The median age was similar between groups. Stroke volume index (39 vs 39 mL/min/m(2)) and cardiac index (2.6 vs 2.5 L/min/m(2)) were similar. Aortic cross-sectional area (3.3 vs 2.8 cm(2)), peak aortic flow (302 vs 261 cm(3)/sec), and myocardial performance index (0.47 vs 0.25) were higher and ejection fraction (50% vs 66%) was lower in Fontan patients. Input impedance (61 vs 83 dyne · sec/cm(5)/m(2)) was lower in Fontan patients. Pulse-wave velocity (488 vs 364 cm/sec), elastic pressure-strain modulus (305 vs 263 torr), and stiffness index (4.15 vs 3.04) were higher in Fontan patients. Total arterial compliance (1.29 vs 1.32 mL/torr/m(2)) and mean power (606 vs 527 mW/m(2)) were similar and total hydraulic power (716 vs 627 mW/m(2)) was higher in Fontan patients. Efficiency and the power cost per unit of forward flow were similar. CONCLUSIONS: Despite stiffer aortas, Fontan patients generate more hydraulic power associated with decreased ventricular function to achieve a similar hydraulic efficiency. In Fontan patients, therapy that is given to improve ventricular function may need to target vascular stiffness as well. This technique may be used to monitor the efficacy of therapeutic interventions.

Echo-Doppler assessment of arterial stiffness in pediatric patients with Kawasaki disease.

BACKGROUND: There is growing evidence to suggest increased arterial stiffness in patients with a history of Kawasaki disease (KD). Pulse-wave velocity (PWV) is the most validated measure of arterial stiffness. The aim of this study was to determine if aortic PWV is increased in children with KD. METHODS: This was a retrospective cohort study. The study cohort was composed of 42 patients with KD (mean age, 9.7 ± 2.0 years) and 44 age-matched control subjects. The primary measure was aortic PWV. Secondary measures included characteristic impedance (Zc), input impedance (Zi), elastic pressure-strain modulus (Ep), and ß stiffness index and the following measures of left ventricular size and function: end-diastolic and end-systolic dimensions, wall thickness in diastole and systole, mass, shortening and ejection fractions, mean velocity of circumferential fiber shortening, and stress at peak systole. The appropriate measures were indexed to body surface area. The aortic stiffness and impedance indexes were derived using an echocardiography-Doppler method. RESULTS: Height, weight, body mass index, and body surface area were similar between the groups. PWV was higher in patients with KD compared with controls (495 vs 370 cm/sec, P = .0008). Zc, Ep, and ß stiffness index were higher in patients with KD, but the difference was not statistically significant. Left ventricular dimensions were all within normal limits, with no differences between the groups. Patients with KD had lower stress at peak systole compared with controls (55 vs 64 g/cm(2), P = .01). There was a significant association between the length of time between the initial diagnosis and testing with PWV (r = 0.32, P = .04) and Zi (r = -0.38, P = .01) in patients with KD. There was no significant association between the arterial stiffness indexes (PWV, Zi, Zc, Ep, and ß stiffness index) and length of fever, age at KD diagnosis, or heart rate. Logistic regression analysis revealed no association between coronary artery lesion classification and length of fever, day of illness at first treatment, age at KD diagnosis, or any of the arterial stiffness indexes. In the control group, there were significant associations between age and heart rate (r = -0.48, P = .001), Zi (r = -0.55, P < .0001), Zc (r = -0.66, P < .0001), and ß stiffness index (r = -0.31, P = .04). There was an association between heart rate and Zc (r = 0.44, P = .003) but no association between heart rate and PWV, Zi, Ep, or ß stiffness index. CONCLUSIONS: Arterial stiffness was increased in children with KD. There was no association between acute-phase KD coronary involvement and PWV. This implies that patients with KD may be at increased cardiovascular risk in the future.

Echo-Doppler assessment of the biophysical properties of the aorta in children with chronic kidney disease.

Chronic kidney disease (CKD) is known to cause increased arterial stiffness, which is an important independent risk factor for adverse cardiovascular events. The purpose of this study was to assess the vascular properties of the aorta (AO) in a group of children with CKD using a noninvasive echocardiography (echo)-Doppler method. We studied 24 children with stages 2 through 5 CKD and 48 age-matched controls. Detailed echocardiographic assessment and echo-Doppler pulse wave velocity (PWV) was performed. Indices of arterial stiffness, including characteristic (Zc) and input (Zi) impedances, elastic pressure-strain modulus (Ep), and arterial wall stiffness index, were calculated. CKD patients underwent full nephrology assessment, and an iohexol glomerular filtration rate was performed, which allowed for accurate assignment of the CKD stage. CKD patients had greater median systolic blood pressure (114 vs. 110 mmHg; p < 0.04) and pulse pressure (51 vs. 40 mmHg; p < 0.001) compared with controls. PWV was similar between groups (358 vs. 344 cm s(-1); p = 0.759), whereas Zi (182 vs. 131 dyne s cm(-5); p < 0.001), Zc (146 vs. 138 dyne s cm(-5); p = 0.05), and Ep (280 vs. 230 mmHg; p < 0.02) were significantly greater in CKD than in controls. Although load-dependent measures of arterial stiffness were greater in non-dialysis dependent CKD patients, PWV was not increased compared with controls. This suggests that the increased arterial stiffness may not be permanent in these pediatric patients with kidney disease.

Economic evaluation of palivizumab in children with congenital heart disease: a Canadian perspective.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants. In children with congenital heart disease (CHD), it is associated with significant morbidity and mortality. Palivizumab is a monoclonal antibody that reduces the number of RSV-associated hospitalizations in children with CHD. We sought to assess cost savings and cost-effectiveness of palivizumab in children < 2 years old with hemodynamically significant CHD in a provincially administered RSV prophylaxis program. METHODS: A cohort of children who received palivizumab (N = 292) from 2003-2007 was compared to a historical cohort of children (N = 412) from 1998-2003 who met the eligibility criteria for palivizumab prior to initiation of the prophylaxis program. Direct and indirect costs and benefits were determined. RESULTS: The direct and indirect costs in the historical cohort were $838 per patient season compared to $9130 per patient season in the palivizumab cohort. Risk of admission was reduced by 42%, and days in hospital were reduced by 83%. The incremental cost of the RSV prophylaxis program was $8292 per patient for 1 RSV season. The incremental cost to prevent 1 day of hospitalization was $15,514. The cost of palivizumab accounted for 87.9% of the cost of prophylaxis. CONCLUSIONS: Palivizumab is clinically effective; however, the cost was exceptionally high relative to the outcomes in this population. Given the financial constraints in a public health care setting, more strict criteria for patient selection or reduced drug costs would improve the cost-effectiveness of RSV prophylaxis.

Echocardiographic Doppler assessment of the biophysical properties of the aorta in pediatric patients with the Marfan syndrome.

In the Marfan syndrome (MS), aortic root involvement is usually clinically monitored according to the aortic sinus of Valsalva dilation. Using an echocardiographic Doppler method in this cross-sectional study, abnormal biophysical properties of the ascending aorta were found in pediatric patients with MS compared with healthy controls but not consistently in association with the aortic sinus of Valsalva dilation.