| 1. |
- Broberg, Olof, et al.
(författare)
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Characterization of Cardiac, Vascular, and Metabolic Changes in Young Childhood Cancer Survivors
- 2021
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood cancer survivors (CCS) are at an increased risk for cardiovascular diseases (CVD). It was the primary aim of this study to determine different measures of cardiac, carotid, lipid, and apolipoprotein status in young adult CCS and in healthy controls. Methods: Cardiac and common carotid artery (CCA) structure and function were measured by ultrasonography. Lipids and apolipoproteins were measured in the blood. Peripheral arterial endothelial vasomotor function was assessed by measuring digital reactive hyperemia index (PAT-RHI) using the Endo-PAT 2000. Results: Fifty-three CCS (20-30 years, 35 men) and 53 sex-matched controls were studied. The CCS cohort was divided by the median dose of anthracyclines into a low anthracycline dose (LAD) group (50-197 mg/m2, n = 26) and a high anthracycline dose (HAD) group (200-486 mg/m2, n = 27). Carotid distensibility index (DI) and endothelial function determined by PAT-RHI were both lower in the CCS groups compared with controls (p < 0.05 and p = 0.02). There was no difference in carotid intima media thickness. Atherogenic apolipoprotein-B (Apo-B) and the ratio between Apo-B and Apoliprotein-A1 (Apo-A1) were higher in the HAD group compared with controls (p < 0.01). Apo-B/Apo-A1-ratio was over reference limit in 29.6% of the HAD group, in 15.4% of LAD group, and in 7.5% of controls (p = 0.03). Measured lipid markers (low density lipoprotein and total cholesterol and triglycerides) were higher in both CCS groups compared with controls (p < 0.05). Systolic and diastolic function were measurably decreased in the HAD group, as evidenced by lower EF (p < 0.001) and lower é-wave (p < 0.005) compared with controls. CCA DI correlated with Apo-B/Apo-A1-ratio and Apo-A1. Follow-up time after treatment correlated with decreased left ventricular ejection fraction (p = 0.001). Conclusion: Young asymptomatic CCS exhibit cardiac, vascular, lipid, and apolipoprotein changes that could account for increased risk for CVD later in life. These findings emphasize the importance of cardiometabolic monitoring even in young CCS.
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| 2. |
- Elkinany, Sherif, et al.
(författare)
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Is Aortic Z-score an Appropriate Index of Beneficial Drug Effect in Clinical Trials in Aortic Aneurysm Disease?
- 2021
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- Aortic Z-score (Z-score) is utilized in clinical trials to monitor the effect of medications on aortic dilation rate in Marfan (MFS) patients. Z-scores are reported in relation to body surface area and therefore are a function of height and weight. However, an information void exists regarding natural, non-pharmacological changes in Z-scores as children age. We had concerns that Z-score decrease attributed to “therapeutic” effects of investigational drugs for Marfan disease connective tissue diseases might simply reflect normal changes (“filling out” of body contour) as children age. This investigation studies natural changes with age in Z-score in normal and untreated MFS children, teasing out normal effects that might erroneously be attributed to drug benefit. (1) We first compared body mass index (BMI) and Z-scores (Boston Children's Hospital calculator) in 361 children with “normal” single echo exams in four age ranges (0 to 1, 5 to 7, 10 to 12, 15 to 18 years). Regression analysis revealed that aging itself decreases ascending Z-score, but not root Z-score, and that increase in BMI with aging underlies the decreased Z-scores. (2) Next, we examined Z-score findings in both “normal” and Marfan children (all pharmacologically untreated) as determined on sequential echo exams over time. Of 27 children without aortic disease with sequential echos, 19 (70%) showed a natural decrease in root Z-score and 24 (89%) showed a natural decrease in ascending Z- score, over time. Of 25 untreated MFS children with sequential echos, 12 (40%) showed a natural decrease in root Z-score and 10 (33%) showed a natural decrease in ascending Z-score. Thus, Z-score is over time affected by natural factors even in the absence of any aneurysmal pathology or medical intervention. Specifically, Z-score decreases spontaneously as a natural phenomenon as children age and with fill out their BMI. Untreated Marfan patients often showed a spontaneous decrease in Z-score. In clinical drug trials in aneurysm disease, decreasing Z-score has been interpreted as a sign of beneficial drug effect. These data put such conclusions into doubt.
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| 3. |
- Jeremiasen, Ida, et al.
(författare)
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Vasodilator therapy for pulmonary hypertension in children : a national study of patient characteristics and current treatment strategies
- 2021
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Ingår i: Pulmonary Circulation. - : John Wiley & Sons. - 2045-8932 .- 2045-8940. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary vasodilator therapy is still often an off-label treatment for pulmonary hypertension in children. The aim of this nationwide register-based study was to assess patient characteristics and strategies for pulmonary vasodilator therapy in young Swedish children. Prescription information for all children below seven years of age at treatment initiation, between 2007 and 2017, was retrieved from the National Prescribed Drug Register, and medical information was obtained by linkage to other registers. All patients were categorized according to the WHO classification of pulmonary hypertension. In total, 233 patients had been prescribed pulmonary vasodilators. The treatment was initiated before one year of age in 61% (N = 143). Sildenafil was most common (N = 224 patients), followed by bosentan (N = 29), iloprost (N = 14), macitentan (N = 4), treprostinil (N = 2) and riociguat (N = 2). Over the study period, the prescription rate for sildenafil tripled. Monotherapy was most common, 87% (N = 203), while 13% (N = 20) had combination therapy. Bronchopulmonary dysplasia (N = 82, 35%) and/or congenital heart defects (N = 156, 67%) were the most common associated conditions. Eight percent (N = 18) of the patients had Down syndrome. Cardiac catheterization had been performed in 39% (N = 91). Overall mortality was 13% (N = 30) during the study period. This study provides an unbiased overview of national outpatient use of pulmonary vasodilator therapy in young children. Few cases of idiopathic pulmonary arterial hypertension were found, but a large proportion of pulmonary hypertension associated with congenital heart defects or bronchopulmonary dysplasia. Despite treatment, mortality was high, and additional pediatric studies are needed for a better understanding of underlying pathologies and evidence of treatment effects.
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| 4. |
- Weismann, Constance G., et al.
(författare)
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Echocardiographic predictors of recoarctation following surgical repair – a Swedish national study
- 2021
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975. ; 111:4, s. 1380-1386
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Tidskriftsartikel (refereegranskat)abstract
- Background Following surgical repair of aortic coarctation (CoA) there is a risk for restenosis (reCoA), particularly in the first year of life. It was the aim of this study to identify reCoA risk factors by analyzing postoperative pre-discharge echocardiograms. Methods Retrospective analysis of echocardiograms of children born operated for CoA in Sweden 2011-2017. Results 253 children were included; median age at surgery 10 days; median follow-up 4.6 years. ReCoA occurred in 34 patients (13%; 74% by 6 months, 91% by 12 months). We generated two reCoA risk models applying a) aortic dimensions and b) the respective Z-scores combined with surgical and demographic factors. We defined reCoA risk categories as low (≤10%), moderate (11-29%), moderate-high (30-49%) and high (≥50%). Patients with a) isthmus ≤3.3mm (1- and 5-year event free survival 38 and 32%) or b) isthmus Z-score ≤-2.8 with a weight at surgery <4.4kg (1- and 5-year event free survival 21 and 16%) were at highest risk for reCoA. Conversely, patients at low risk had a) isthmus >3.7mm and distal aortic arch >3.5mm (1- and 5-year event free survival 97 and 97%), and b) isthmus and proximal aortic arch Z-score >-2.8 or operative weight >4.4kg with an isthmus Z-score <=-2.8 with (1- and 5-year event free survival 97 and 97%). Conclusion ReCoA risk can be predicted based on postoperative pre-discharge echocardiographic variables in combination with surgical and demographic factors. We suggest tailoring follow-up intervals individually according to the predicted reCoA risk.
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| 5. |
- Weismann, Constance G., et al.
(författare)
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Multimodal Assessment of Vascular and Ventricular Function in Children and Adults With Bicuspid Aortic Valve Disease
- 2021
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Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media SA. - 2297-055X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bicuspid aortic valve (BAV), the most common congenital cardiac anomaly, has been associated with an aortopathy, increased aortic stiffness and diastolic dysfunction. The involved mechanisms and impact of age remain unclear. It was the aim of this study to characterize arterial and cardiac function, their correlation, and the effect of age in children and adults with a history of BAV. Methods: Multimodal cardiovascular assessment included echocardiography, ascending aortic distensibility, common carotid intima media thickness [cIMT], parameters of wave reflection [central (cAIx75) and peripheral (pAIx75) augmentation index corrected to a heart rate of 75/min, aging index (AI)], carotid-femoral pulse wave velocity [cfPWV], and endothelial function (EndoPAT). Multivariable linear regression and correlation analyses were performed. Results: We included 47 BAV patients and 84 controls (age 8–65 years). Ascending aortic stiffness, pulse wave reflection (cAIx75, pAIx75, and AI) and central blood pressure were significantly increased in patients with BAV. However, PWV, cIMT, and endothelial function were not significantly different from controls. BAV patients had marginally reduced diastolic (E': β = −1.5, p < 0.001) but not systolic function compared to controls. Overall, all parameters of arterial stiffness had moderate-strong correlations with diastolic dysfunction and age. In the BAV group, ascending aortic distensibility had the strongest correlation with diastolic dysfunction. Conclusions: BAV is associated with increased proximal arterial stiffness and wave reflection. However, PWV and cIMT are not increased, and endothelial function is preserved. This suggests that the mechanism of arterial and cardiac stiffening is different from patients with acquired heart diseases.
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| 6. |
- Weismann, Constance G., et al.
(författare)
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Multimodal assessment of vascular and ventricular function in children and adults with repaired aortic coarctation
- 2021
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 323, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coarctation of the Aorta (CoA) is associated with increased aortic stiffness and diastolic left ventricular dysfunction. The mechanisms involved and impact of age remain unclear. It was the aim of this study to characterize arterial and cardiac function, their correlation, and the effect of age in children and adults with repaired CoA. Methods: Multimodal cardiovascular assessment from the ascending aorta to microcirculation and endothelial function was performed prospectively. Statistical analyses included multivariable linear regression and correlation of vascular parameters with age and diastolic function. Results: Fifty-seven patients with well-repaired CoA and 77 healthy controls were included (age 8–59). There was no significant difference in age, gender, body surface area and BMI between the groups. Ascending aortic distensibility was decreased while common carotid intima media thickness, central augmentation index corrected to a heart rate of 75/min [Aix75], peripheral Aix75 and aging index were increased in the CoA group. Interestingly, in a subgroup analysis of CoA patients with tricuspid vs. bicuspid aortic valves (BAV), only the latter had increased Aix75. Carotid-femoral pulse wave velocity [cfPWV], reactive hyperemia index and microcirculation were not significantly different between CoA and control patients. Diastolic function was impaired in the CoA group relative to controls. Both diastolic function and age correlated moderate-strongly with arterial parameters. Conclusions: Patients with well repaired CoA have increased proximal arterial stiffness which correlates with diastolic function and age. Increased Aix75 may be attributed to a high prevalence of associated BAV. Neither cfPWV nor peripheral endothelial or microcirculatory function are impaired.
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