The Pediatric Heart Network (PHN) trial showed similar efficacy of β-blockers (BB) and angiotensin receptor blockers (ARB) for aortic root dilation in Marfan syndrome, but the impact on prescription ...practices is unknown. We hypothesized BB and ARB prescriptions would increase after the trial results were published (2014). Prescription data (2007–2016) were obtained from outpatient encounters (IBM Marketscan) for Marfan syndrome patients (6 months–25 years old). Excluding 2014 as a washout period, we analyzed two intervals: 2007–2013 and 2015–2016. Medication categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug. Interrupted time-series analysis assessed immediate level change after publication and change in slope for the trend pre- and post-publication. Odds ratios (OR) and 95% confidence intervals from logistic regressions and generalized estimating equation methods accounted for correlation of prescriptions within patients. In 1499 patients (age 14.1 ± 6.1 years, 59% female) seen 2007–2013, BB trended lower OR 0.91 (0.89, 0.93),
p
< 0.001 and ARB trended higher OR 1.12 (1.07, 1.18),
p
< 0.001, while combination, ACEI, and no drug remained stable. This trend persisted, but was not significant, for BB OR 0.54 (0.27, 1.08),
p
= 0.37 and ARB OR 1.91 (0.55, 6.69),
p
= 0.31 in 2015–2016. Combination, ACEI, and no drug remained similar. In short term follow-up, changes in prescription practices following publication of the PHN trial were not statistically significant. This may be due to a change seen prior to publication with early adoption of ARBs that was maintained after confirmation of their effectiveness.
Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the ...current standard therapy in most centers.
We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events.
From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean ±SD age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups.
Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).
Objectives To test prospectively the reproducibility and feasibility of endothelial pulse amplitude testing (Endo-PAT), a novel Food and Drug Administration-approved technology, in healthy ...adolescents. Study design We performed Endo-PAT testing on 2 different days separated by no more than 7 days in 30 healthy fasting adolescents, ages 13 to 19 years, to assess reproducibility and feasibility. The reported level of discomfort, as measured on a pain scale of 1 to 5, was documented. Results The mean difference in paired Endo-PAT indices was 0.12 (95% CI, –0.09-0.33; P = .24; intraclass correlation coefficient, 0.78), and the within-subject variation of Endo-PAT index was 0.16. The Endo-PAT index on test days 1 and 2 were 1.91 ± 0.57 and 1.78 ± 0.51 (mean plus or minus SD), respectively. All attempted studies (100%) were completed (95% CI, 88%-100%), and all completed studies (100%) could be analyzed (95% CI, 88%-100%). The median pain score was 1 on both days. Conclusion In healthy adolescents, Endo-PAT is feasible and has excellent reproducibility. This technology may provide an easy and reliable means of assessing endothelial function in the pediatric population.
Objective Successful mitral valve replacement in young children is limited by the lack of small prosthetic valves. Supra-annular prosthesis implantation can facilitate mitral valve replacement with a ...larger prosthesis in children with a small annulus, but little is known about its effect on the outcomes of mitral valve replacement in young children. Methods One hundred eighteen children underwent mitral valve replacement at 5 years of age or younger from 1976–2006. Mitral valve replacement was supra-annular in 37 (32%) patients. Results Survival was 74% ± 4% at 1 year and 56% ± 5% at 10 years but improved over time (10-year survival of 83% ± 7% from 1994–2006). Factors associated with worse survival included earlier mitral valve replacement date, age less than 1 year, complete atrioventricular canal, and additional procedures at mitral valve replacement, but not supra-annular mitral valve replacement. As survival improved during our more recent experience, the risks of supra-annular mitral valve replacement became apparent; survival was worse among patients with a supra-annular prosthesis after 1991. A pacemaker was placed in 18 (15%) patients within 1 month of mitral valve replacement and was less likely in patients who had undergone supra-annular mitral valve replacement. Among early survivors, freedom from redo mitral valve replacement was 72% ± 5% at 5 years and 45% ± 7% at 10 years. Twenty-one patients with a supra-annular prosthesis underwent redo mitral valve replacement. The second prosthesis was annular in 15 of these patients and upsized in all but 1, but 5 required pacemaker placement for heart block. Conclusions Supra-annular mitral valve replacement was associated with worse survival than annular mitral valve replacement in our recent experience. Patients with supra-annular mitral valve replacement were less likely to have operative complete heart block but remained at risk when the prosthesis was subsequently replaced.
The Pediatric Heart Network randomized trial of atenolol versus losartan in the Marfan syndrome showed no treatment differences in the rates of aortic-root growth or clinical outcomes. In this report ...we present treatment effects on aortic stiffness and determine whether baseline aortic stiffness predicts aortic-root growth and clinical outcomes. Echocardiograms at 0, 6, 12, 24, and 36 months from 608 subjects (6 months to 25 years) who met original Ghent criteria and had a maximum aortic-root z-score (ARz) >3 were centrally reviewed. Stiffness index (SI) and elastic modulus (EM) were calculated for aortic root and ascending aorta. Data were analyzed using multivariable mixed effects modeling and Cox regression. Heart rate–corrected aortic-root SI over 3 years decreased with atenolol but did not change with losartan (−0.298 ± 0.139 vs 0.141 ± 0.139/year, p = 0.01). In the entire cohort, above-median aortic-root SI (>9.1) and EM (>618 mm Hg) predicted a smaller annual decrease in ARz (p ≤0.001). Upper-quartile aortic-root EM (>914 mm Hg) predicted the composite outcome of aortic-root surgery, dissection, or death (hazard ratio 2.17, 95% confidence interval 1.02 to 4.63, p = 0.04). Crude 3-year event rates were 10.4% versus 3.2% for higher versus lower EM groups. In conclusion, atenolol was associated with a decrease in aortic-root SI, whereas losartan was not. Higher baseline aortic-root SI and EM were associated with a smaller decrease in ARz and increased risk for clinical outcomes. These data suggest that noninvasive aortic stiffness measures may identify patients at higher risk of progressive aortic enlargement and adverse clinical outcomes, potentially allowing for closer monitoring and more aggressive therapy.
Background Optimally treated patients with coarctation of the aorta remain at risk for late vascular dysfunction. The effect of treatment modality on vascular function is unknown. The LOVE-COARCT ...(Long-term Outcomes and Vascular Evaluation After Successful Coarctation of the Aorta Treatment) study was done to compare vascular function in patients with coarctation of the aorta treated with surgery, balloon dilation (BD), or stent implantation. Methods and Results In treated coarctation of the aorta patients without residual coarctation, we prospectively compared aortic stiffness by applanation tonometry and cardiac magnetic resonance; endothelial function by endothelial pulse amplitude testing; blood pressure ( BP ) phenotype by office BP , ambulatory BP monitoring, and BP response to exercise; left ventricular mass by cardiac magnetic resonance; and blood biomarkers of endothelial function, inflammation, vascular wall function, and extracellular matrix. Participants included 75 patients treated with surgery (n=28), BD (n=23), or stent (n=24). Groups had similar age at enrollment, coarctation of the aorta severity, residual gradient, and metabolic profile, but differed by age at treatment. Prevalence of systemic hypertension, aortic stiffness, endothelial function, and left ventricular mass were similar among treatment groups. However, BD patients had more-distensible ascending aortas, lower peak systolic BP during exercise, less impairment in diurnal BP variation, and lower inflammatory biomarkers. Results were unchanged after adjustment for potential confounders, including age at treatment. Conclusions In our cohort of patients without residual coarctation, treatment modality was not associated with major vascular outcomes, even though there were some favorable vascular characteristics in the BD patients. Although this suggests that choice of treatment modality should continue to be driven by likelihood of achieving a good anatomical result, more long-term studies are required to assess the clinical significance of the more-optimal results of secondary markers of vascular function in BD patients. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 03262753.
Objective To evaluate adherence of overweight and obese adolescents to a live video lifestyle intervention. The impact on vascular and functional health was also assessed. Study design Twenty ...adolescents 14.5 ± 2.1 years of age with body mass index z-score 1.94 ± 0.43 were enrolled. The 12-week intervention included 3-times-weekly videoconference sessions with a trainer and weekly diet consultations. Adherence was evaluated by completion rate and percentage of sessions attended. Vascular health indices and traditional cardiovascular risk factors were obtained at baseline and study end. Results Seventeen participants (85%) completed the intervention. The participants attended 93 ± 11% of scheduled sessions. Reasons for absences included illness/injury (23%), school activities (21%), holidays (18%), forgetting the appointment (8%), Internet connectivity issues (7%), and family emergency (7%). Significant changes were observed in waist-hip ratio (0.87 ± 0.08 vs 0.84 ± 0.08, P = .03), total (159 ± 27 vs 147 ± 23 mg/dL, P = .004) and low-density lipoprotein cholesterol levels (91 ± 20 vs 81 ± 18 mg/dL, P = .004), volume of inspired oxygen per heartbeat at peak exercise (69 ± 16 vs 72 ± 15%, P = .01), and functional movement score (13 ± 2 vs 17 ± 1, P < .001). Participants with abnormal vascular function at baseline showed improvement in endothelial function and arterial stiffness indices ( P = .01 and P = .04, respectively). Conclusions A 12-week live video intervention promotes adherence among overweight and obese adolescents and shows promise for improving vascular and functional health. Integrating telehealth into preventive care has the potential to improve cardiovascular health in the youth at risk.
Background
Pediatric heart transplant (PedHtx) patients have increased cardiovascular risk profiles that affect their long‐term outcomes and quality of life. We designed a 12‐ to 16‐week diet and ...exercise intervention delivered via live video conferencing to improve cardiovascular health. Our methodology and baseline assessment of the first 13 enrolled patients are reported.
Methods
Inclusion criteria are as follows: (a) 8‐19 years old; (b) heart transplant >12 months; (c) ability to fast overnight; (d) cardiac clearance by cardiologist; and (e) presence of an adult at home during exercise sessions for patients <14 years old. Exclusion criteria are as follows: (a) acute illness; (b) latex allergy; (c) transplant rejection <3 months ago; and (d) multi‐organ transplantation. The intervention consists of one diet and three exercise sessions weekly via live video conferencing. Study visits are conducted at baseline, intervention completion, and end of maintenance period.
Results
A total of 13 participants (15.2 2.3 years) have been enrolled. Median percent‐predicted VO2 max was 56.8 20.7% (10 patients <70%). Ten patients had abnormal endothelial function (reactive hyperemia index <1.9; 1.4 0.325) and 11 patients had stiff arteries (pulse wave velocity ≧5.5 m/s for 15‐19 years, ≧4.5 m/s for 8‐14 years; 5.6 0.7 m/s). Patients had suboptimal diets (saturated fat: 22.7 23.8 g/d, sodium: 2771 1557 mg/d) and were sedentary at a median of 67.5 13.8% of their time.
Conclusions
Baseline assessment confirms that PedHtx patients have abnormal cardiac, vascular, and functional health indices, poor dietary habits, and are sedentary. These results support the rationale to test the feasibility and impact of a non‐pharmacologic lifestyle intervention in this patient population.
BACKGROUND
Aortic pulse wave velocity (PWV) and augmentation index (AIx) are markers of vascular health and have recently been used in pediatric clinical trials. However, there are limited data on ...standardization of these measurements in pediatrics. The objective of this study was to prospectively test the feasibility and reproducibility of PWV and AIx in children and adolescents.
METHODS
We performed arterial tonometry on 2 different days within 2 weeks in 40 healthy subjects aged 10-19 years. PWV and AIx were measured in triplicate on each visit.
RESULTS
The visits were separated by a mean of 3.08±3.7 days. We obtained PWV in 77 of 80 (96%) visits and AIx in 76 of 80 (95%) visits in triplicate. Intraclass correlation coefficients (ICCs) for PWV were 0.61 (95% confidence interval (CI) = 0-0.86) when at least 2 measurements and 0.92 (95% CI = 0-1) when 3 measurements were obtained at each visit that met the quality criteria established for adults by the manufacturer (n = 17 and 3 paired visits, respectively). For AIx, ICCs were 0.78 (95% CI = 0.58-0.88) and 0.81 (95% CI = 0.63-0.90) when measurements with an operator index ≥80, a measure of the quality of the waveform, were included (n = 39 and 36 paired visits, respectively).
CONCLUSIONS
Arterial applanation tonometry is feasible and reproducible in healthy children and adolescents. AIx has excellent intervisit reproducibility, whereas the intervisit reproducibility of PWV relies on acquisition of multiple measurements that meet quality criteria established for adults. These results have implications for the methodology of future pediatric clinical trials in a population at increasingly higher risk for premature atherosclerosis.
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