Sudden cardiac arrest in infants and children: proposal for a diagnostic workup to identify the etiology. An 18-year multicenter evaluation in the Netherlands.

Sudden cardiac arrest (SCA) studies are often population-based, limited to sudden cardiac death, and excluding infants. To guide prevention opportunities, it is essential to be informed of pediatric SCA etiologies. Unfortunately, etiologies frequently remain unresolved. The objectives of this study were to determine paediatric SCA etiology, and to evaluate the extent of post-SCA investigations and to assess the performance of previous cardiac evaluation in detecting conditions predisposing to SCA. In a retrospective cohort (2002-2019), all children 0-18 years with out-of-hospital cardiac arrest (OHCA) referred to Erasmus MC Sophia Children's Hospital or the Amsterdam UMC (tertiary-care university hospitals), with cardiac or unresolved etiologies were eligible for inclusion. SCA etiologies, cardiac and family history and etiologic investigations in unresolved cases were assessed. The etiology of arrest could be determined in 52% of 172 cases. Predominant etiologies in children ≥ 1 year (n = 99) were primary arrhythmogenic disorders (34%), cardiomyopathies (22%) and unresolved (32%). Events in children < 1 year (n = 73) were largely unresolved (70%) or caused by cardiomyopathy (8%), congenital heart anomaly (8%) or myocarditis (7%). Of 83 children with unresolved etiology a family history was performed in 51%, an autopsy in 51% and genetic testing in 15%. Pre-existing cardiac conditions presumably causative for SCA were diagnosed in 9%, and remained unrecognized despite prior evaluation in 13%. CONCLUSION: SCA etiology remained unresolved in 83 of 172 cases (48%) and essential diagnostic investigations were often not performed. Over one-fifth of SCA patients underwent prior cardiac evaluation, which did not lead to recognition of a cardiac condition predisposing to SCA in all of them. The diagnostic post-SCA approach should be improved and the proposed standardized pediatric post-SCA diagnostics protocol may ensure a consistent and systematic evaluation process increasing the diagnostic yield. WHAT IS KNOWN: • Arrests in infants remain unresolved in most cases. In children > 1 year, predominant etiologies are primary arrhythmia disorders, cardiomyopathy and myocarditis. • Studies investigating sudden cardiac arrest are often limited to sudden cardiac death (SCD) in 1 to 40 year old persons, excluding infants and successfully resuscitated children. WHAT IS NEW: • In patients with unresolved SCA events, the diagnostic work up was often incompletely performed. • Over one fifth of victims had prior cardiac evaluation before the arrest, with either a diagnosed cardiac condition (9%) or an unrecognized cardiac condition (13%).

Sex-specific differences in outcome and risk stratification of ventricular arrhythmias in implantable cardioverter defibrillator patients.

AIMS: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women. METHODS AND RESULTS: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4-4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P < 0.001], as was time to mortality (HR 1.37, P = 0.003). In women, only secondary prevention ICD therapy (HR 1.82, P < 0.01) was associated with ADT, whereas higher age (HR 1.20, P < 0.001), absence of left bundle branch block (HR 0.72, P = 0.01), and secondary prevention therapy (HR 1.80, P < 0.001) were independently associated with ADT in men. None of the observed parameters showed a distinctive sex-specific pattern in ADT. CONCLUSIONS: Male ICD patients were at higher risk of ADT and death compared with female ICD patients, irrespective of an ischaemic or non-ischaemic underlying cardiomyopathy. Our study highlights the importance to stratify outcomes of ICD trials by sex, as study results differ between men and women. However, none of the available clinical parameters showed a clear sex-specific relation to ventricular arrhythmias. As a consequence, sex-specific risk stratification models of SCD using commonly available clinical parameters could not be derived.

Multiplane/3D transesophageal echocardiography monitoring to improve the safety and outcome of complex transvenous lead extractions.

Both transesophageal echocardiography (TEE) and intracardiac echocardiography have been used to assist transvenous lead extractions. The clinical utility of continuous echocardiographic monitoring during the procedure is still debated, with different reports supporting opposite findings. In cases where the procedure is expected to be difficult, we propose adding a continuous TEE monitoring using a static 3D/multiplane probe in mid-esophageal position, with digital remote manipulation of the field of view. This approach may improve the chances of a successful extraction, increase safety, or even guide the entire intervention. We present here a short case series where continuous monitoring by TEE played an important role.

Procedural and long-term outcome after catheter ablation of idiopathic outflow tract ventricular arrhythmias: comparing manual, contact force, and magnetic navigated ablation.

Aims: Currently, comparative data on procedural and long-term clinical outcome of outflow tract (OT) idiopathic ventricular arrhythmia (IVA) ablation with manual (MAN), contact force (CF), and magnetic navigation system (MNS) ablation are lacking. The aim of this study was to compare the procedural and long-term clinical outcome of MAN, CF, and MNS ablation of OT IVAs. Methods and results: Seventy-three patients (31 MAN, 17 CF, and 25 MNS patients; consecutive per group) with OT IVA, who underwent catheter ablation in our centre were analysed. Procedural success rates (success at the end of the procedure), procedural data and long-term follow-up data were compared. Baseline patient demographics were comparable. Procedural success rates were similar (MAN 81%, 71% CF, and MNS 92%; P = 0.20). Median fluoroscopy time was shorter in the MNS group: MAN 29 (16-38), CF 37 (21-46), and MNS 13 (10-20) min (P = 0.002 for MNS vs. CF and MAN). The overall complication rate was: MAN 10%, CF 0%, and MNS 0% (P = 0.12). Median follow-up was: MAN 2184 (1672-2802), CF 1721 (1404-1913), and MNS 3031 (2524-3286) days (P <0.001). Recurrences occurred in MAN 46%, CF 50%, and MNS 46% (P = 0.97). Repeat procedures were performed in MAN 20%, CF 40%, and MNS 33% (P = 0.32). Conclusion: Procedural and long-term clinical outcome of OT IVA ablation are equal for MAN, CF, and MNS. MNS has a favourable procedural safety profile due to the shorter fluoroscopy time compared with MAN and CF.

Comparative study of the failure rates among 3 implantable defibrillator leads.

BACKGROUND: After the introduction of the Biotronik Linox S/SD high-voltage lead, several cases of early failure have been observed. OBJECTIVE: The purpose of this article was to assess the performance of the Linox S/SD lead in comparison to 2 other contemporary leads. METHODS: We used the prospective Erasmus MC ICD registry to identify all implanted Linox S/SD (n = 408), Durata (St. Jude Medical, model 7122) (n = 340), and Endotak Reliance (Boston Scientific, models 0155, 0138, and 0158) (n = 343) leads. Lead failure was defined by low- or high-voltage impedance, failure to capture, sense or defibrillate, or the presence of nonphysiological signals not due to external interference. RESULTS: During a median follow-up of 5.1 years, 24 Linox (5.9%), 5 Endotak (1.5%), and 5 Durata (1.5%) leads failed. At 5-year follow-up, the cumulative failure rate of Linox leads (6.4%) was higher than that of Endotak (0.4%; P < .0001) and Durata (2.0%; P = .003) leads. The incidence rate was higher in Linox leads (1.3 per 100 patient-years) than in Endotak and Durata leads (0.2 and 0.3 per 100 patient-years, respectively; P < .001). A log-log analysis of the cumulative hazard for Linox leads functioning at 3-year follow-up revealed a stable failure rate of 3% per year. The majority of failures consisted of noise (62.5%) and abnormal impedance (33.3%). CONCLUSION: This study demonstrates a higher failure rate of Linox S/SD high-voltage leads compared to contemporary leads. Although the mechanism of lead failure is unclear, the majority presents with abnormal electrical parameters. Comprehensive monitoring of Linox S/SD high-voltage leads includes remote monitoring to facilitate early detection of lead failure.

Surgical outcome of discrete subaortic stenosis in adults: a multicenter study.

BACKGROUND: Discrete subaortic stenosis is notable for its unpredictable hemodynamic progression in childhood and high reoperation rate; however, data about adulthood are scarce. METHODS AND RESULTS: Adult patients who previously underwent surgery for discrete subaortic stenosis were included in this retrospective multicenter cohort study. Mixed-effects and joint models were used to assess the postoperative progression of discrete subaortic stenosis and aortic regurgitation, as well as reoperation. A total of 313 patients at 4 centers were included (age at baseline, 20.2 years [25th-75th percentile, 18.4-31.0 years]; 52% male). Median follow-up duration was 12.9 years (25th-75th percentile, 6.2-20.1 years), yielding 5617 patient-years. The peak instantaneous left ventricular outflow tract gradient decreased from 75.7±28.0 mm Hg preoperatively to 15.1±14.1 mm Hg postoperatively (P<0.001) and thereafter increased over time at a rate of 1.31±0.16 mm Hg/y (P=0.001). Mild aortic regurgitation was present in 68% but generally did not progress over time (P=0.76). A preoperative left ventricular outflow tract gradient ≥80 mm Hg was a predictor for progression to moderate aortic regurgitation postoperatively. Eighty patients required at least 1 reoperation (1.8% per patient-year). Predictors for reoperation included female sex (hazard ratio, 1.53; 95% confidence interval, 1.02-2.30) and left ventricular outflow tract gradient progression (hazard ratio, 1.45; 95% confidence interval, 1.31-1.62). Additional myectomy did not reduce the risk for reoperation (P=0.92) but significantly increased the risk of a complete heart block requiring pacemaker implantation (8.1% versus 1.7%; P=0.005). CONCLUSIONS: Survival is excellent after surgery for discrete subaortic stenosis; however, reoperation for recurrent discrete subaortic stenosis is not uncommon. Over time, the left ventricular outflow tract gradient slowly increases and mild aortic regurgitation is common, although generally nonprogressive over time. Myectomy does not show additional advantages, and because it is associated with an increased risk of complete heart block, it should not be performed routinely.

Ascending aortic diameters in congenital aortic stenosis: cardiac magnetic resonance versus transthoracic echocardiography.

OBJECTIVES/BACKGROUND: Congenital aortic stenosis (AS) is the most common obstructive left heart lesion in the young adult population and often complicated by aortic dilatation. Our objective was to evaluate accuracy of aortic imaging with transthoracic echocardiography (TTE) compared with cardiac magnetic resonance (CMR). METHODS: Aortic diameters were measured at 4 levels by CMR and TTE. Agreement and concordance were assessed by Pearson's correlation and Bland-Altman analysis. RESULTS: Fifty-nine patients (age 33 ± 8 years; 66% male) with congenital AS and a bicuspid aortic valve (BAV) were included. Aortic diameters were generally smaller with TTE than with CMR. The best correlation was found at the level of the sinotubular junction (R(2) = 0.78) with a bias of 1.46 mm (limits of agreement: -5.47 to +8.39 mm). In patients with an aortic aneurysm >40 mm (n = 29) the correlation and agreement between TTE and CMR were found to be less good when compared with patients with normal aortic diameters, especially at the level of the proximal ascending aorta. The correlation and agreement between both imaging modalities were better in patients with type 1 BAV compared with type 2 BAV. Intra- and interobserver variability was smaller with CMR (1.8-5.9%) compared with TTE (6.9-15.0%). CONCLUSIONS: CMR was found to be superior to TTE for imaging of the aorta in patients with congenital AS, especially at the level of the proximal ascending aorta when an aortic aneurysm is present. Therefore, ideally CMR should be performed at least once to ensure an ascending aortic aneurysm is not missed.

Natural history of discrete subaortic stenosisin adults: a multicentre study.

AIMS: Discrete subaortic stenosis (DSS) is often diagnosed early in life and known for its sometimes rapid haemodynamic progression in childhood and strong association with aortic regurgitation (AR). However, data about the evolution of DSS in adulthood are scarce. Therefore, we aimed to evaluate the natural history of DSS, and identify risk factors for the progression of DSS, AR, and intervention-free survival. METHODS AND RESULTS: Conservatively managed adult DSS patients were included in this retrospective multicentre cohort study. Mixed-effects and joint models were used to assess the progression of DSS and AR, and intervention-free survival. Longitudinal natural history data were available for 149 patients [age 20 (IQR: 18-34) years, 48% male]. Sixty patients (40.3%) had associated congenital heart defects (CHDs). The median follow-up duration was 6.3 (IQR: 3.0-12.4) years. The baseline peak left ventricular outflow tract (LVOT) gradient was 32.3 ± 17.0 mmHg and increased by 0.8 ± 0.1 mmHg/year. While the baseline LVOT gradient (P = 0.891) or age (P = 0.421) did not influence the progression rate, the presence of associated CHD was associated with faster progression (P = 0.005). Mild AR was common (58%), but did not significantly progress over time (P = 0.701). The median intervention-free survival was 16 years and associated with the baseline LVOT gradient [hazard ratio (HR) = 3.9 (95% CI: 2.0-7.6)], DSS progression [HR = 2.6 (95% CI: 2.0-3.5)], and AR [HR = 6.4 (95% CI 2.6-15.6)]. CONCLUSION: In contrast to children, DSS progresses slowly in adulthood. In particular, patients with associated CHD are at risk for faster progression and should be monitored cautiously. Discrete subaortic stenosis progression is not influenced by the baseline LVOT gradient or age. Mild AR is common, but non-progressive over time.

Effects of rosuvastatin on progression of stenosis in adult patients with congenital aortic stenosis (PROCAS Trial).

Recent trials have failed to show that statin therapy halts the progression of calcific aortic stenosis (AS). We hypothesized that statin therapy in younger patients with congenital AS would be more beneficial, because the valve is less calcified. In the present double-blind, placebo-controlled trial, 63 patients with congenital AS (age 18 to 45 years) were randomly assigned to receive either 10 mg of rosuvastatin daily (n = 30) or matched placebo (n = 33). The primary end point was the progression of peak aortic valve velocity. The secondary end points were temporal changes in the left ventricular mass, ascending aortic diameter, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The median follow-up was 2.4 years (interquartile range 1.9 to 3.0). The mean increase in peak velocity was 0.05 ± 0.21 m/s annually in the rosuvastatin group and 0.09 ± 0.24 m/s annually in the placebo group (p = 0.435). The annualized change in the ascending aorta diameter (0.4 ± 1.7 mm with rosuvastatin vs 0.5 ± 1.6 mm with placebo; p = 0.826) and left ventricular mass (1.1 ± 15.8 g with rosuvastatin vs -3.7 ± 30.9 g with placebo; p = 0.476) were not significantly different between the 2 groups. Within the statin group, the NT-proBNP level was 50 pg/ml (range 19 to 98) at baseline and 21 pg/ml (interquartile range 12 to 65) at follow-up (p = 0.638). NT-proBNP increased from 40 pg/ml (interquartile range 20 to 92) to 56 pg/ml (range 26 to 130) within the placebo group (p = 0.008). In conclusion, lipid-lowering therapy with rosuvastatin 10 mg did not reduce the progression of congenital AS in asymptomatic young adult patients. Interestingly, statins halted the increase in NT-proBNP, suggesting a potential positive effect of statins on cardiac function in young patients with congenital AS.

Predictors of pregnancy complications in women with congenital heart disease.

AIMS: Data regarding pregnancy outcome in women with congenital heart disease (CHD) are limited. METHODS AND RESULTS: In 1802 women with CHD, 1302 completed pregnancies were observed. Independent predictors of cardiac, obstetric, and neonatal complications were calculated using logistic regression. The most prevalent cardiac complications during pregnancy were arrhythmias (4.7%) and heart failure (1.6%). Factors independently associated with maternal cardiac complications were the presence of cyanotic heart disease (corrected/uncorrected) (P < 0.0001), the use of cardiac medication before pregnancy (P < 0.0001), and left heart obstruction (P < 0.0001). New characteristics were mechanical valve replacement (P = 0.0014), and systemic (P = 0.04) or pulmonary atrioventricular valve regurgitation related with the underlying (moderately) complex CHD (P = 0.03). A new risk score for cardiac complications is proposed. The most prevalent obstetric complications were hypertensive complications (12.2%). No correlation of maternal characteristics with adverse obstetric outcome was found. The most prevalent neonatal complications were premature birth (12%), small for gestational age (14%), and mortality (4%). Cyanotic heart disease (corrected/uncorrected) (P = 0.0003), mechanical valve replacement (P = 0.03), maternal smoking (P = 0.007), multiple gestation (P = 0.0014), and the use of cardiac medication (P = 0.0009) correlated with adverse neonatal outcome. CONCLUSION: In our tertiary CHD cohort, cardiac, obstetric, and neonatal complications were frequently encountered, and (new) correlations of maternal baseline data with adverse outcome are reported. A new risk score for adverse cardiac complications is proposed, although prospective validation remains necessary.

Fertility, pregnancy and delivery in women after biventricular repair for double outlet right ventricle.

OBJECTIVES: To investigate outcome of pregnancy and fertility in women with double outlet right ventricle (DORV). METHODS: Using 2 congenital heart disease registries, 21 female patients with DORV (aged 18-39 years) were retrospectively identified. Detailed recordings of each patient and their completed (>20 weeks gestation) pregnancies were recorded. RESULTS: Overall, 10 patients had 19 pregnancies, including 3 spontaneous miscarriages (16%). During the 16 live birth pregnancies, primarily (serious) noncardiac complications were observed, e.g. premature labor/delivery (n = 7 and n = 3, respectively), small for gestational age (n = 4), preeclampsia (n = 2) and recurrence of congenital heart disease (n = 2). Except for postpartum endocarditis and deterioration of subpulmonary obstruction, only mild cardiac complication pregnancies were recorded. Two women with children reported secondary female infertility. Several menstrual cycle disorders were reported: secondary amenorrhea (n = 4), primary amenorrhea (n = 3) and oligomenorrhea (n = 2). CONCLUSION: Successful pregnancy in women with DORV is possible. Primarily noncardiac complications were observed and only few (minor) cardiac complications. Infertility and menstrual cycle disorders appear to be more prevalent.

Smoking and its effects on mortality in adults with congenital heart disease.

AIMS: To describe smoking habits in adults with congenital heart disease (ACHD) and to assess the relationship between smoking exposure and cardiovascular mortality. METHODS: Data on smoking history and cardiovascular mortality were extracted from the Euro Heart Survey on adult congenital heart disease - a retrospective cohort study, that included patients diagnosed with 1 of 8 subgroups of ACHD (Atrial Septal Defects, Ventricular Septal Defects, Marfan Syndrome, Aortic Coarctation, Tetralogy of Fallot (ToF), Transposition of the Great Arteries (TGA), Fontan circulation, and Cyanotic disease). RESULTS: Complete data of 3375 ACHD patients (median age 28 years) were available for analysis. At inclusion, 9.3% (n=314) were current smokers and 4.2% (n=142) of the patients had smoked in the past. During a median follow-up of 5.1 years, 101 patients (3%) died. In the majority of cases the cause of death was cardiovascular (n=81; 80%). Kaplan-Meier and Cox survival analysis for each of the defects separately showed a significantly increased age and sex-adjusted cardiovascular mortality associated with smoking exposure in TGA patients (Hazard ratio 4.2 (95% CI 1.0-16.8); P=0.044). Also in ToF mortality was higher amongst smokers, though not significantly (HR 3.4 (95% CI 0.6-18.5); P=0.15). In the remaining defects no relationship between smoking and cardiovascular mortality was observed. CONCLUSION: The prevalence of smoking amongst ACHD patients is relatively low. Smoking exposure is associated with increased cardiovascular mortality in patients with TGA. Prospective long-term follow-up studies are necessary.

Outcome of pregnancy in women with congenital heart disease: a literature review.

A search of peer-reviewed literature was conducted to identify reports that provide data on complications associated with pregnancy in women with structural congenital heart disease (CHD). This review describes the outcome of 2,491 pregnancies, including 377 miscarriages (15%) and 114 elective abortions (5%). Important cardiac complications were seen in 11% of the pregnancies. Obstetric complications do not appear to be more prevalent. In complex CHD, premature delivery rates are high, and more children are small for gestational age. The offspring mortality was high throughout the spectrum and was related to the relatively high rate of premature delivery and recurrence of CHD.