Abstract
Aims
Our objective was to assess changes in the birth prevalence of CHD over a half-century in a high-resource, nationwide setting, as well as changes in the prevalence of cardiac ...interventions in this population.
Methods and results
The Swedish National Patient and Cause of Death registers were linked to estimate the annual rates of CHD and cardiac interventions among live-born infants from 1970 to 2017. Additionally, separate estimates were obtained by lesion complexity, from mild to the most complex forms of CHD. Overall, the numbers of live-born infants with a CHD identified varied from 624 to 2459 annual cases, with rates increasing steadily from 5.7 to an average of 20 per 1000 live births at the end of the study period, and with a more pronounced increase from 1996 to 2005. The largest increase over time was observed for mild CHD lesions. Overall, the proportion of cardiac interventions among patients with CHD declined from 40.7% in 1970 to below 15.0% after 2014. However, in the most complex CHD lesion groups, overall cardiac interventions increased from 57.1 to 76.8% in patients with conotruncal defects and from 32.8 to 39.5% in those with severe non-conotruncal defects.
Conclusion
The live-birth prevalence of CHD in Sweden more than tripled during the past half-century, most likely resulting from more accurate diagnostic capabilities. The largest increase over time was observed among patients with simple defects. During the same period, overall cardiac interventions decreased whereas interventions for the most complex CHD groups increased.
Graphical Abstract
Graphical Abstract
Summary of the method and main result for the study of prevalence of congenital heart disease in Sweden.
Background Hypoplastic left heart syndrome is associated with significant morbidity and mortality. We aimed to assess the influence of left ventricular morphology and choice of shunt on adverse ...outcome in patients with hypoplastic left heart syndrome and stage 1 palliation. Methods and Results This was a retrospective analysis of patients with hypoplastic left heart syndrome with stage 1 palliation between 1999 and 2018 in Sweden. Patients (n=167) were grouped based on the anatomic subtypes aortic-mitral atresia, aortic atresia-mitral stenosis (AA-MS), and aortic-mitral stenosis. The left ventricular phenotypes including globular left ventricle (Glob-LV), miniaturized and slit-like left ventricle (LV), and the incidence of major adverse events (MAEs) including mortality were assessed. The overall mortality and MAEs were 31% and 41%, respectively. AA-MS (35%) was associated with both mortality (all other subtypes versus AA-MS: interstage-I: hazard ratio HR, 2.7;
=0.006; overall: HR, 2.2;
=0.005) and MAEs (HR, 2.4;
=0.0009). Glob-LV (57%), noticed in all patients with AA-MS, 61% of patients with aortic stenosis-mitral stenosis, and 19% of patients with aortic atresia-mitral atresia, was associated with both mortality (all other left ventricular phenotypes versus Glob-LV: interstage-I: HR, 4.5;
=0.004; overall: HR, 3.4;
=0.0007) and MAEs (HR, 2.7;
=0.0007). There was no difference in mortality and MAEs between patients with AA-MS and without AA-MS with Glob-LV (
>0.15). Patients with AA-MS (35%) or Glob-LV (38%) palliated with a Blalock-Taussig shunt had higher overall mortality compared with those palliated with Sano shunts, irrespective of the stage 1 palliation year (AA-MS: HR, 2.6;
=0.04; Glob- LV: HR, 2.1;
=0.03). Conclusions Glob-LV and AA-MS are independent morphological risk factors for adverse short- and long- term outcome, especially if a Blalock-Taussig shunt is used as part of stage 1 palliation. These findings are important for the clinical management of patients with hypoplastic left heart syndrome.
Severe left-sided cardiac obstructions are associated with high morbidity and mortality if not detected in time. The correct prenatal diagnosis of coarctation of the aorta (CoA) is difficult. Fetal ...cardiac magnetic resonance imaging (CMR) may improve the prenatal diagnosis of complex congenital heart defects. Flow measurements in the ascending aorta could aid in predicting postnatal CoA, but its accurate visualization is challenging.
To compare the flow in the descending aorta (DAo) and umbilical vein (UV) in fetuses with suspected left-sided cardiac obstructions with and without the need for postnatal intervention and healthy controls by fetal phase-contrast CMR flow. A second objective was to determine if adding fetal CMR to echocardiography (echo) improves the fetal CoA diagnosis.
Prospective fetal CMR phase-contrast flow in the DAo and UV and echo studies were conducted between 2017 and 2022.
A total of 46 fetuses with suspected left-sided cardiac obstructions 11 hypoplastic left heart syndrome (HLHS), five critical aortic stenosis (cAS), and 30 CoA and five controls were included. Neonatal interventions for left-sided cardiac obstructions (
= 23) or comfort care (
= 1 with HLHS) were pursued in all 16 fetuses with suspected HLHS or cAS and in eight (27%) fetuses with true CoA. DAo or UV flow was not different in fetuses with and without need of intervention. However, DAo and UV flows were lower in fetuses with either retrograde isthmic systolic flow DAo flow 253 (72) vs. 261 (97) ml/kg/min,
= 0.035; UV flow 113 (75) vs. 161 (81) ml/kg/min,
= 0.04 or with suspected CoA and restrictive atrial septum DAo flow 200 (71) vs. 268 (94) ml/kg/min,
= 0.04; UV flow 89 vs. 159 (76) ml/kg/min,
= 0.04 as well as in those without these changes. Adding fetal CMR to fetal echo predictors for postnatal CoA did not improve the diagnosis of CoA.
Fetal CMR-derived DAo and UV flow measurements do not improve the prenatal diagnosis of left-sided cardiac obstructions, but they could be important in identifying fetuses with a more severe decrease in blood flow across the left side of the heart. The physiological explanation may be a markedly decreased left ventricular cardiac output with subsequent retrograde systolic isthmic flow and decreased total DAo flow.
Background Norwood surgery provides a palliative surgical option for hypoplastic left heart syndrome and has been available in Sweden since 1993. The practice of prenatal ultrasound screening was ...gradually implemented in the same era, resulting in an increased prenatal detection rate. Our primary aims were to study changes in the incidence of live births, prenatal detection rate, and the termination of pregnancies over time. The secondary aims were to study the proportion of live-borns undergoing surgery and to identify factors that influenced whether surgery was or was not performed. Methods and Results Neonates with hypoplastic left heart syndrome with aortic atresia born 1990-2010 were identified through national databases, surgical files, and medical records. The fetal incidence was estimated from the period when prenatal screening was rudimentary. The study period was divided into the presurgical, early surgical, and late surgical periods. The incidence was calculated as the overall yearly incidence for each time period and sex separately. Factors influencing whether surgery was performed were analyzed using Cox-logistic regression. The incidence at live birth decreased from 15.4 to 8.4 per 100 000. The prenatal detection rate increased from 27% to 63%, and terminations increased from 19% to 56%. The odds of having surgery was higher in the late period and higher in the group with prenatal diagnosis. Conclusions We observed a decrease in incidence of live-borns with hypoplastic left heart syndrome aortic atresia. There was in increase in prenatal detection rate and an increase in termination of pregnancy. The proportion of live-borns who underwent surgery increased between time periods.
ECG abnormalities have been linked to adverse changes in right ventricular (RV) morphology and poor clinical outcomes in repaired Tetralogy of Fallot (rTOF). Our aim was to describe how ECG changes ...progress in early and intermediate follow-up and whether types of surgical strategy at the time of primary repair affected these changes.
We studied patients with rTOF born 2000-2018 operated at our institution. Seven time points in relation to primary repair, follow-up, and pulmonary valve replacement (PVR) were identified. Patients correct with valve sparing repair (VSR), trans-annular patch (TAP) including with a monocusp valve (TAP + M) and with at least 3 ECGs were included. PQ interval, QRS duration, dispersion, and fragmentation, QTc duration and dispersion, JTc as well as presence of a right bundle branch block (RBBB) were analyzed. Medical records were reviewed for demographic and surgical data.
Two hundred nineteen patients with 882 ECGs were analyzed with a median follow-up time of 12.3 years (8.4, 17) with 41 (19%) needing PVR during the study period. QRS duration increased at time of primary repair to discharge from 66 msec (IQR 12) to 129 msec (IQR 27) (
< 0.0001) and at 1- and 6- year follow-up but showed only a modest and temporary decrease after PVR. QTc increased at the time of primary repair as well as prior to PVR. PQ interval showed a small increase at the time of primary repair, was at its highest prior to PVR and decreased with PVR. Type of surgical repair affected mainly QTc and JTc and was consistently longer in the TAP + M group until PVR. In VSR, QTc and JTc were prolonged initially compared to TAP but were similar after 1 year. After PVR, there were no differences in adverse ECG changes between surgical groups.
PQ interval and QRS duration best correspond to the assumed volume load whereas the relationship with QTc and JTc is more complex, suggesting that these represent more complex remodeling of the myocardium. Before PVR, QTc and JTc are longer in the TAP + M group which may be due to a longer surgical incision.
The aim of the study was to explore what adolescents with congenital heart disease (CHD) view as important in the preparation for the transfer to adult care. We performed interviews in four focus ...groups with adolescents (14–18 years old) at four university hospitals in Sweden. Data was analysed using qualitative content analysis. The analysis revealed one main category;
Becoming a manager of the condition
and four subcategories;
Sufficient knowledge about the health, Be a participant in the care, Parental support,
and
Communicate with others about the health.
The adolescents’ ages differentiated the discussion in the groups. The older adolescents seemed to have more interest in transition planning, information and transfer. The younger described more frustrations about communication and handling the disease.
Conclusion
: To become a manager of the CHD in daily life, the adolescents want disease specific knowledge, which should be communicated in a developmentally appropriate way. Adolescents want to participate and be involved in the transition process. They need support and guidance in how to communicate their CHD. Parental support is fundamental but it change over time. Moreover, peer-support is becoming more significant during the transition process.
What is Known:
• Transition during adolescence and transfer to adult care for adolescents with CHD is complex, and there is a shift in roles.
• Adolescents often have poor knowledge and understanding about their heart condition and the consequences.
What is New:
• Adolescents call for disease specific information regarding health issues of importance for them in daily life.
• Communicating the disease with other is a challenge- peer support from other adolescents with CHD could be a facilitator.
Arrhythmia is related to heart rate variability (HRV), which reflects the autonomic nervous regulation of the heart. We hypothesized that autonomic nervous ganglia, located at the junction of the ...superior vena cava’s entrance to the heart, may be affected during the bidirectional Glenn procedure (BDG), resulting in reduced HRV. We aimed to investigate changes in heart rate and HRV in a cohort of children with univentricular heart defects, undergoing stepwise surgery towards total cavopulmonary connection (TCPC), and compare these results with healthy controls. Twenty four hours Holter-ECG recordings were obtained before BDG (
n
= 47), after BDG (
n
= 47), and after total cavopulmonary connection (TCPC) (
n
= 45) in patients and in 38 healthy controls. HRV was analyzed by spectral and Poincaré methods. Age-related
z
scores were calculated and compared using linear mixed effects modeling. Total HRV was significantly lower in patients before BDG when compared to healthy controls. The mean heart rate was significantly reduced in patients after BDG compared to before BDG. Compared to healthy controls, patients operated with BDG had significantly reduced heart rate and reduced total HRV. Patients with TCPC showed reduced heart rate and HRV compared with healthy controls. In patients after TCPC, total HRV was decreased compared to before TCPC. Heart rate was reduced after BDG procedure, and further reductions of HRV were seen post-TCPC. Our results indicate that autonomic regulation of cardiac rhythm is affected both after BDG and again after TCPC. This may be reflected as, and contribute to, postoperative arrhythmic events.
Abstract Background Exercise intolerance is frequent among Fontan patients and an important determinant for quality of life. This study investigated the hemodynamic causes of impaired exercise ...capacity in Fontan patients with particular focus on the influence of stroke volume index (SVI) and heart rate (HR). Methods and results In 38 Fontan patients, peak oxygen consumption (VO2 ), SVI and HR were recorded during incremental load exercise test and compared with 19 age and gender matched controls. SVI (ml/m2 ) was lower in patients than controls during warm-up (2826–31 vs. 3530–39, p = 0.0093), at submaximal (4037–43 vs. 5551–59, p < 0.0001) and at maximal exercise (3835–40 vs. 5451–58, p < 0.0001). Similarly, HR (% of expected maximum) was lower in patients at warm-up (4543–48% vs. 6457–64%, p < 0.0001), submaximal (7168–75% vs 8582–88%, p < 0.0001) and maximal exercise (8480–88% vs. 9795–99%, p < 0.0001). Furthermore, SVI dropped 14% (from 4441–48 to 3835–40 ml/m2 ) in Fontan patients from the peak plateau to maximal exercise vs. 5% (from 5753–61 to 5451–58 ml/m2 ) in controls, p < 0.0001. The low SVI and HR explained 67% and 20% of the difference in peak VO2 between Fontan patients and controls respectively. Conclusion SVI decreased significantly in Fontan patients near the end of maximal effort exercise. The low SVI at maximal exercise was the most important hemodynamic factor limiting exercise capacity in Fontan patients, whereas chronotropic impairment had a smaller impact. The low SVI and HR at maximal exercise accounted for the difference in peak VO2 between Fontan patients and controls in this study. Clinical trial registration http://www.cvk.sum.dk/CVK/Home/English.aspx (protocol nr: H-3-2010-045).
Purpose
Numerous studies have investigated causes of warfarin dose variability in adults, whereas studies in children are limited both in numbers and size. Mechanism-based population modelling ...provides an opportunity to condense and propagate prior knowledge from one population to another. The main objectives with this study were to evaluate the predictive performance of a theoretically bridged adult warfarin model in children, and to compare accuracy in dose prediction relative to published warfarin algorithms for children.
Method
An adult population pharmacokinetic/pharmacodynamic (PK/PD) model for warfarin, with
CYP2C9
and
VKORC1
genotype, age and target international normalized ratio (INR) as dose predictors, was bridged to children using allometric scaling methods. Its predictive properties were evaluated in an external data set of children 0–18 years old, including comparison of dose prediction accuracy with three pharmacogenetics-based algorithms for children.
Results
Overall, the bridged model predicted INR response well in 64 warfarin-treated Swedish children (median age 4.3 years), but with a tendency to overpredict INR in children ≤2 years old. The bridged model predicted 20 of 49 children (41 %) within ± 20 % of actual maintenance dose (median age 7.2 years). In comparison, the published dosing algorithms predicted 33–41 % of the children within ±20 % of actual dose. Dose optimization with the bridged model based on up to three individual INR observations increased the proportion within ±20 % of actual dose to 70 %.
Conclusion
A mechanism-based population model developed on adult data provides a promising first step towards more individualized warfarin therapy in children.
BACKGROUND—The Fontan procedure has improved survival in children with functionally univentricular hearts. With time, however, complications such as reduced exercise capacity are seen more ...frequently. Exercise intolerance is multifactorial, but pulmonary vascular resistance probably plays a crucial role. Elevated pulmonary vascular resistance has been associated with raised levels of endothelin-1, which are common both before and after Fontan operations. Treatment with endothelin-1 receptor antagonists could theoretically improve cardiopulmonary hemodynamics and exercise capacity. The aim of this study was therefore to examine the efficacy and safety of bosentan in Fontan patients.
METHODS AND RESULTS—Seventy-five adolescents and adults were randomized 1:1 to 14 weeks of treatment with bosentan or placebo. Cardiopulmonary exercise test, functional class, blood samples, and quality-of-life questionnaires were evaluated at baseline and at the end of treatment. Sixty-nine patients (92%) completed the study. Peak oxygen consumption increased 2.0 mL·kg·min (from 28.7 to 30.7 mL·kg·min) in the bosentan group compared with 0.6 mL·kg·min (from 28.4 to 29.0 mL·kg·min) in the placebo group (P=0.02). Cardiopulmonary exercise test time increased by 0.48 minute (from 6.79 to 7.27 minutes) versus 0.08 minute (from 6.94 to 7.02 minutes; P=0.04). Nine bosentan-treated patients improved 1 functional class, whereas none improved in the placebo group (P=0.0085). Side effects were mild and occurred equally in both groups. No serious adverse effects were seen, and no patients had liver enzyme levels above the 3-fold upper limit.
CONCLUSIONS—Bosentan improves exercise capacity, exercise time, and functional class in Fontan patients without serious adverse events or hepatotoxicity.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01292551.
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