Holter study of heart rate variability in children and adolescents with long QT syndrome.

OBJECTIVES: This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta-blocker therapy (BB) and compare it to healthy controls. METHODS: Heart rate variability (HRV), using power spectrum analysis, was analyzed in 575 Holter recordings from 116 children with LQTS and in 69 healthy children. The data were categorized into four age-groups and four heart rate (HR) ranges. RESULTS: In LQT1 and LQT2, increasing HR corresponded to significantly lower low (LF) and high frequency (HF) compared to controls. Total power (PTOT) was lower in all LQT1 age-groups compared to controls at HR 120-140 bpm (1-15 years: p < .01; 15-18 years: p = .03). At HR 80-100, LQT1 patients aged 1-10 years had lower HF than LQT2 patients (1-5 years: p = .05; 5-10 years: p = .02), and LQT2 patients aged 15-18 years had lower HF than LQT1 patients (p < .01). Symptomatic patients aged 10-15 years had lower PTOT at HR 100-120 bpm than asymptomatic patients (p = .04). LQT1 girls aged 10-15 and 15-18 years had a lower PTOT (10-15 years: p = .04; 15-18 years: p = .02) than boys. CONCLUSION: This study shows a correlation between HR and changes in HRV parameters. At higher HRs, LQTS patients generally had lower HRV values than controls, suggesting an abnormal autonomic response. These results may strengthen the link between physical activity and arrhythmias in LQTS.

Endocardial pacing compared to epicardial left ventricle pacing and right ventricle pacing: A single-center long-term experience in a pediatric population.

BACKGROUND AND AIMS: Pediatric pacing is usually performed as epicardial pacing in small children in need of pacemaker therapy. Epicardial pacing compared with transvenous pacing for pediatric complete atrioventricular block (CAVB) has different strengths and weaknesses. The epicardial left ventricular wall position of the lead has been considered superior, in terms of contraction pattern, compared to a transvenous right ventricular stimulation. We aimed to compare QRS duration and cardiac function before and after the switch from epicardial to transvenous pacing in a pediatric population. METHODS: Pediatric patients with congenital or acquired CAVB, who underwent a switch from epicardial-to transvenous pacing at our center from 2005 to 2021, were identified through the national ICD- and Pacemaker Registry. Data regarding clinical status, ECG, and echocardiography before and after the switch and at last follow-up were collected. RESULTS: We included 15 children. The median age at the switch was 6.7 (4.4-11.7) years with a median weight of 21 (15-39) Kg. The median QRS duration with the transvenous systems was 136 (128-152) ms vs. a QRS duration during epicardial stimulation of 150 (144-170) ms with a median difference in QRS duration of 14 (6-20) ms. Children with a post-surgical AV block had a broader QRS duration, both with epicardial and endocardial stimulation. Before the switch, there was one patient with impaired left ventricular function (LVF) but with normal left ventricular end-diastolic diameters. After the switch, one patient developed symptomatic LV dysfunction with the recovery of LVF at the last follow-up after being implanted with a cardiac resynchronization therapy device. CONCLUSIONS: Our report of pediatric patients after switching from epicardial to transvenous pacing shows how transvenous pacing is not inferior to epicardial pacing in terms of QRS duration and no significant deterioration of cardiac function was detectable.

Cardiac response to water activities in children with Long QT syndrome type 1.

BACKGROUND: Swimming is a genotype-specific trigger in long QT syndrome type 1 (LQT1). OBJECTIVE: To examine the autonomic response to water activities in children and adolescents with LQT1. METHODS: In this cross-sectional study, LQT1 patients were age and sex matched to one healthy control subject. Electrocardiograms (ECGs) were recorded during face immersion (FI), swimming, diving, and whole-body submersion (WBS). Heart rate (HR) and heart rate variability (HRV) was measured. The high frequency (HF) component of HRV was interpreted to reflect parasympathetic activity, while the low frequency (LF) component was interpreted as reflecting the combined influence of sympathetic and parasympathetic activity on autonomic nervous modulation of the heart. RESULTS: Fifteen LQT1 patients (aged 7-19 years, all on beta-blocker therapy) and fifteen age and sex matched non-medicated controls were included. No significant ventricular arrhythmias were observed in the LQT1 population during the water activities. Out of these 15 matched pairs, 12 pairs managed to complete FI and WBS for more than 10 seconds and were subsequently included in HR and HRV analyses. In response to FI, the LQT1 group experienced a drop in HR of 48 bpm, compared to 67 bpm in the control group (p = 0.006). In response to WBS, HR decreased by 48 bpm in the LQT1 group and 70 bpm in the control group (p = 0.007). A significantly lower PTOT (p < 0.001) and HF (p = 0.011) component was observed before, during and after FI in LQT1 patients compared with the controls. Before, during and after WBS, a significantly lower total power (p < 0.001), LF (p = 0.002) and HF (p = 0.006) component was observed in the LQT1 patients. CONCLUSION: A significantly lower HR decrease in response to water activities was observed in LQT1 subjects on beta-blocker therapy, compared to matched non-medicated controls. The data suggests an impaired parasympathetic response in LQT1 children and adolescents. An aberrant autonomic nervous system (ANS) response may cause an autonomic imbalance in this patient group.

Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry.

AIMS: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. METHODS AND RESULTS: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. CONCLUSION: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator.

Pacing therapy in children with isolated complete atrioventricular block: a retrospective study of pacing system survival and pacing-related complications in a national cohort.

AIMS: To evaluate pacing system survival and complications to pacemaker (PM) therapy in children with isolated complete atrioventricular block (CAVB). METHODS AND RESULTS: We performed a nationwide retrospective study of children diagnosed before 15 years of age with isolated CAVB and PM treatment. Between 1983 and 2012, 127 patients underwent PM-implantations at 3.2 (0-17) [median (range)] years and were followed for 11 (0.6-19) years. An endocardial or epicardial PM system was implanted in 72 and 55 patients, respectively. A total of 306 pacing leads (76% steroid-eluting) were implanted. Pacing system survival was significantly affected by age, with a higher risk of a new intervention for children aged <1 month at first implantation. Lead survival of the steroid-eluting leads at 5 and 10 years was 90 and 81%, respectively, with no difference between epicardial and endocardial systems. Complications leading to revision of the pacing system occurred in 24% of the patients. Patients aged <1 month at first PM implantation had a five-fold increased risk for a complication to occur. Dividing the cohort according to year of first procedure showed that those who had their first implantation ≥2002 had fewer complications and also lead- and pacing system survival was better in the later cohort. CONCLUSION: Pacing system survival and complications to PM therapy in young patients with isolated CAVB were significantly affected by age, with low age at PM implantation constituting a risk factor. Endocardial and epicardial pacing systems showed no significant differences in performance.

Cardiac Troponin T in Healthy Full-Term Infants.

In this prospective cohort study of healthy full-term infants, we hypothesized that high-sensitivity cardiac troponin T (hs-cTnT) would be elevated in cord blood, compared with adult reference values, and that it would further increase over the first days of age. Cardiac troponin T has been shown to be significantly increased in healthy full-term newborns compared with adult reference values, but there is no established reference range. Most studies of cTnT in newborns have been performed before the introduction of high-sensitivity cTnT (hs-cTnT) assay. We conducted a study including 158 full-term newborns, at Stockholm South General Hospital. High-sensitivity cTnT was analyzed in umbilical cord blood and at 2-5 days of age. Median hs-cTnT (interquartile range) in cord blood was 34(26-44) ng/L; 99th percentile 88 ng/L. Median hs-cTnT at 2-5 days of age was 92(54-158) ng/L; 99th percentile 664 ng/L. We conclude that hs-cTnT is elevated in cord blood in healthy, full-term newborn infants compared with adult reference values, and that it increases significantly during the first days of life. Our findings further underline the need of caution when using hs-cTnT as a measurement of cardiac impact in newborns.

Sinus node dysfunction in patients with Fontan circulation: could heart rate variability be a predictor for pacemaker implantation?

Sinus node dysfunction (SND) causes significant morbidity in patients after Fontan surgery. Heart rate variability (HRV) reflects the autonomic regulation of the heart, and changes in HRV have been associated with SND in adults. We aimed to study whether changes in HRV could be detected in 24-h electrocardiographic (ECG) recordings in Fontan patients with SND. We compared HRV results from two patient groups; patients with Fontan circulation who later required a pacemaker due to severe SND (n = 12) and patients with Fontan circulation and SND, without indication for pacemaker treatment (n = 11), with two control groups; patients with Fontan circulation without SND (n = 90) and healthy controls (n = 66). The Poincaré plot index SD2 (representing changes in heart rate over 24-h) and the very low-frequency (VLF) HRV component were significantly higher in both SND groups, both compared with healthy controls and patients with Fontan circulation without SND. In SND patients with pacemakers, SD2 and VLF were slightly reduced compared to SND patients without pacemaker (p = 0.06). In conclusion, in Fontan patients with SND the HRV is significantly higher compared to healthy controls and Fontan patients without SND. However, in patients with severe SND requiring pacemaker, SD2 and VLF tended to be lower than in patients with SND without pacemaker, which could indicate a reduced diurnal HRV in addition to the severe bradycardia. This is a small study, but our results indicate that HRV analysis might be a useful method in the follow-up of Fontan patients regarding development of SND.

Comorbidity and long-term outcome in patients with congenital heart block and their siblings exposed to Ro/SSA autoantibodies in utero.

OBJECTIVE: Congenital heart block (CHB) may develop in fetuses of Ro/SSA autoantibody-positive women. Given the rarity of CHB, information on comorbidity and complications later in life is difficult to systematically collect for large groups of patients. We therefore used nation-wide healthcare registers to investigate comorbidity and outcomes in patients with CHB and their siblings. METHODS: Data from patients with CHB (n= 119) and their siblings (n= 128), all born to anti-Ro/SSA-positive mothers, and from matched healthy controls (n= 1,190) and their siblings (n= 1,071), were retrieved from the Swedish National Patient Register. Analyses were performed by Cox proportional hazard modelling. RESULTS: Individuals with CHB had a significantly increased risk of cardiovascular comorbidity, with cardiomyopathy and/or heart failure observed in 20 (16.8%) patients versus 3 (0.3%) controls, yielding a HR of 70.0 (95% CI 20.8 to 235.4), and with a HR for cerebral infarction of 39.9 (95% CI 4.5 to 357.3). Patients with CHB also had a higher risk of infections. Pacemaker treatment was associated with a decreased risk of cerebral infarction but increased risks of cardiomyopathy/heart failure and infection. The risk of systemic connective tissue disorder was also increased in patients with CHB (HR 11.8, 95% CI 4.0 to 11.8), and both patients with CHB and their siblings had an increased risk to develop any of 15 common autoimmune conditions (HR 5.7, 95% CI 2.83 to 11.69 and 3.6, 95% CI 1.7 to 8.0, respectively). CONCLUSIONS: The data indicate an increased risk of several cardiovascular, infectious and autoimmune diseases in patients with CHB, with the latter risk shared by their siblings.

Outcome in young patients with isolated complete atrioventricular block and permanent pacemaker treatment: A nationwide study of 127 patients.

BACKGROUND: Subgroups of pacemaker (PM)-treated children with isolated complete atrioventricular block are at risk of developing left ventricular (LV) dysfunction. OBJECTIVES: We aimed to compare the long-term outcome in anti-SSA-Ro/SSB-La antibody-exposed (AB+) and unexposed (AB-) patients and identify preimplantation variables associated with poor outcome. METHODS: In total, 127 PM-treated patients aged 0-17 years with isolated complete atrioventricular block were studied retrospectively. RESULTS: Sixty-three patients were diagnosed prenatally, of whom 92% were AB+. Before PM treatment, fractional shortening (FS) z-score was significantly lower in AB+ patients than in AB- patients (-0.14 ± 3.6 vs 2.03 ± 2.3). Before PM implantation, there were sex differences (male/female) in median time from diagnosis to PM implantation (0.2 years vs 1.0 years), median neonatal heart rate (50 beats/min vs 60 beats/min), left ventricular end-diastolic dimension (LVEDD) z-score (2.68 ± 1.41 vs 1.74 ± 1.40), and FS (-0.19 ± 3.38 vs 1.42 ± 2.98). The median age at PM implantation was 3.2 years, and median follow-up was 8.7 years. At follow-up, LVEDD and FS did not differ significantly between AB+ and AB- patients, but LVEDD was higher in patients diagnosed before 1 month of age. Nine patients (8%) developed LV dysfunction, and 4 died. LV dysfunction was associated with diagnosis before 1 month of age and abnormal LV function before PM implantation. CONCLUSION: LV dysfunction at follow-up was seen only in cases diagnosed before 1 month, with abnormal echocardiography before PM implantation. Boys had a more compromised cardiac status and were paced at an earlier age than girls. Fetal AB exposure and male sex were related to abnormal LV function before PM therapy, but not at follow-up.

Long-term growth of children with autoantibody-mediated congenital heart block.

AIM: To analyse growth of children with and without congenital heart block (CHB) born to anti-Ro/SSA positive mothers from birth to 18 years of age, using a population-based cohort of Swedish CHB patients. METHODS: Medical records for siblings with (n = 72) and without (n = 60) CHB born 1973-2009 to anti-Ro/SSA positive mothers were retrieved from child healthcare centres and school health services and used to extract data on growth from birth to 18 years. RESULTS: Compared with reference standards, children with CHB were retarded in weight by 0.75-1.0 SD from birth to 2-3 years of age. Thereafter, the CHB children started to catch up, reaching the reference standards at 9-11 years of age. Pacemaker treatment was not correlated with the catch-up in growth. Individuals with CHB were retarded in both weight and height from birth to 9-11 years of age when compared to siblings without CHB, who did not demonstrate restriction in these measurements. CONCLUSION: Presence of CHB is a more important predictor of growth restriction than maternal rheumatic disease and foetal anti-Ro/SSA exposure. The restriction persists for several years after birth, despite pacemaker treatment, which highlights the importance of follow-up of children with CHB regarding nutrition and growth.

Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern.

OBJECTIVE: Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. METHODS: The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. RESULTS: There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (p<0.05).Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (p<0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. CONCLUSION: This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.

Progression to first-degree heart block in preschool children exposed in utero to maternal anti-SSA/Ro52 autoantibodies.

AIMS: To study the children exposed in utero to maternal anti-SSA/Ro52 antibodies in terms of impaired atrioventricular (AV) conduction or disturbed myocardial performance, and to investigate the ability of prenatal Doppler to predict conduction abnormalities during childhood. METHODS: Fifty-seven children exposed in utero to anti-SSA/Ro52 antibodies were grouped in accordance with (A) prolonged AV time intervals in utero by Doppler or (B) normal findings and examined by ECG, 24-hour ECG and echocardiography. RESULTS: PR interval on ECG was longer in group A (n = 16) compared with that of group B (n = 41), 140 ± 24 ms vs. 121 ± 13 ms (p < 0.01). Six cases of 1°Atrioventricular block (AVB) developed in group A, giving an estimated prevalence of 10.5%, (95% confidence interval; 4.4-22.2%), progressing from normal sinus rhythm at 1 month of age. Prenatal Doppler predicted development of 1°AVB at follow-up with a sensitivity of 100%, Positive predictive value (PPV) 37.5%, LR+ 5.1, and Negative predictive value (NPV) 100%. Children in group A had a slightly higher myocardial performance index in flow and tissue Doppler imaging recordings. CONCLUSIONS: Ten per cent of children exposed in utero to anti-SSA/Ro52, with a normal ECG at birth or 1 month of age, progressed to 1°AVB during preschool years. Cases at risk can be identified by prenatal Doppler echocardiography.

Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients.

BACKGROUND: Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome. METHODS AND RESULTS: We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000-2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1-21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age < 20 weeks, ventricular rate ≤ 50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥ 1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4 ± 2.9 versus 24.9 ± 4.9 weeks; P=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy. CONCLUSIONS: Risk factors associated with a poor outcome were gestation < 20 weeks, ventricular rate ≤ 50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.

[Tricuspid valve stenosis--an serious complication to Port-a-cath]. / Trikuspidalisstenos--en allvarlig komplikation till Port-a-cath.

Tricuspid valve stenosis and occlusion of superior vena cava are severe complications to Port-a-cath. In a child with SLE, symptoms started to develop about five to seven years after Port-a-cath insertion and cyclophosphamid injections. The patient developed hepatomegaly with abdominal and venous distension. Open heart surgery was necessary to remove the catheter. At operation it was found that the catheter was placed adjacent and through the tricuspid valve. The valve was severely stenosed with thrombus formation. The catheter and thrombus were removed, commissurotomy and bicuspidization of the valve and chordeal replacement performed to achieve an acceptable functional result. The superior vena cava was repaired with a pericardial patch. Retrospective analyses of the echocardiograms and chest x-rays show that the catheter was nearly related to the tricuspid valve and with the tip in the right ventricle. In such circumstances it is recommended with early withdrawal of the catheter, and in patients with immunological disease the indwelling time should be considered and limited.

Redundant pacing in a child.

A 4-year-old boy with congenital complete atrioventricular block (CCAVB) and pacemaker (PM) dependency, received a redundant pacemaker. Two separate leads were implanted in the right ventricle, and connected to a dual chamber PM. The two pacing channels were both programmed so that each lead could compensate for the other in case of threshold elevation. The follow-up was uneventful despite exit block on one of the leads.