STEAM-SASHA: a novel approach for blood- and fat-suppressed native T1 measurement in the right ventricular myocardium.

OBJECTIVE: The excellent blood and fat suppression of stimulated echo acquisition mode (STEAM) can be combined with saturation recovery single-shot acquisition (SASHA) in a novel STEAM-SASHA sequence for right ventricular (RV) native T1 mapping. MATERIALS AND METHODS: STEAM-SASHA splits magnetization preparation over two cardiac cycles, nulling blood signal and allowing fat signal to decay. Breath-hold T1 mapping was performed in a T1 phantom and twice in 10 volunteers using STEAM-SASHA and a modified Look-Locker sequence at peak systole at 3T. T1 was measured in 3 RV regions, the septum and left ventricle (LV). RESULTS: In phantoms, MOLLI under-estimated while STEAM-SASHA over-estimated T1, on average by 3.0% and 7.0% respectively, although at typical 3T myocardial T1 (T1 > 1200 ms) STEAM-SASHA was more accurate. In volunteers, T1 was higher using STEAM-SASHA than MOLLI in the LV and septum (p = 0.03, p = 0.006, respectively), but lower in RV regions (p > 0.05). Inter-study, inter-observer and intra-observer coefficients of variation in all regions were < 15%. Blood suppression was excellent with STEAM-SASHA and noise floor effects were minimal. DISCUSSION: STEAM-SASHA provides accurate and reproducible T1 in the RV with excellent blood and fat suppression. STEAM-SASHA has potential to provide new insights into pathological changes in the RV in future studies.

Cardiac MRI predictors of good long-term outcomes in patients with repaired TOF.

BACKGROUND: Risk stratification in patients with repaired tetralogy of Fallot (rTOF) have focused on poor clinical outcomes while predictors of a benign clinical course have not been characterized. OBJECTIVE: The goal of this study was to Identify cardiac magnetic resonance (CMR) markers of a good clinical course late after TOF repair. METHODS: Clinical and CMR data from the International Multicenter TOF Registry (INDICATOR) were analyzed. The primary outcome was time to the earliest occurrence of a composite of death, aborted sudden death, and sustained ventricular tachycardia (VT). The secondary outcome was time to the earliest occurrence of atrial arrhythmia, nonsustained VT, and NYHA class >II. Multinomial regression was used to identify predictors of the 3-category outcome: (a) good outcome, defined as freedom from the primary AND secondary outcomes at age 50 years; (b) poor outcome, defined as presence of the primary outcome before age 50 years; and (c) intermediate outcome, defined as not fulfilling criteria for good or poor outcomes. RESULTS: Among 1088 eligible patients, 96 had good outcome, 60 experienced poor outcome, and 932 had intermediate outcome. Patients were age 25.8±10.8 years at the time of the index CMR. Median follow-up was 5.8 years (IQR 3.0, 9.9) after CMR in event-free patients. By univariate analysis, smaller right ventricular (RV) end-systolic and end-diastolic volume index, smaller left ventricular end-systolic volume index, higher right and left ventricular ejection fraction, lower right and left ventricular mass index, and lower left ventricular mass/volume ratio were associated with good outcome. Multivariable modeling identified higher RV ejection fraction (OR 2.38 per 10% increase, P = .002) and lower RV mass index (OR 1.72, per 10 g/m2 decrease, P = .002) as independently associated with good outcome after adjusting for age at CMR. Classification and regression tree analysis identified important thresholds associated with good outcome that were specific to patients age ≥37 years at the time of CMR; these were RV ejection fraction ≥42% and RV mass index <39 g/m2. CONCLUSIONS: Adults with rTOF and no more than mild RV dysfunction combined with no significant RV hypertrophy are likely to be free from serious adverse clinical events into their sixth decade of life and may require less frequent cardiac testing.

Global prevalence of congenital heart disease in school-age children: a meta-analysis and systematic review.

BACKGROUND: Congenital heart disease (CHD) is the commonest birth defect. Studies estimating the prevalence of CHD in school-age children could therefore contribute to quantifying unmet health needs for diagnosis and treatment, particularly in lower-income countries. Data at school age are considerably sparser, and individual studies have generally been of small size. We conducted a literature-based meta-analysis to investigate global trends over a 40-year period. METHODS AND RESULTS: Studies reporting on CHD prevalence in school-age children (4-18 years old) from 1970 to 2017 were identified from PubMed, EMBASE, Web of Science and Google Scholar. According to the inclusion criteria, 42 studies including 2,638,475 children, reporting the prevalence of unrepaired CHDs (both pre-school diagnoses and first-time school-age diagnoses), and nine studies including 395,571 children, specifically reporting the prevalence of CHD first diagnosed at school ages, were included. Data were combined using random-effects models. The prevalence of unrepaired CHD in school children during the entire period of study was 3.809 (95% confidence intervals 3.075-4.621)/1000. A lower proportion of male than female school children had unrepaired CHD (OR = 0.84 [95% CI 0.74-0.95]; p = 0.001). Between 1970-1974 and 1995-1999, there was no significant change in the prevalence of unrepaired CHD at school age; subsequently there was an approximately 2.5-fold increase from 1.985 (95% CI 1.074-3.173)/1000 in 1995-1999 to 4.832 (95% CI 3.425-6.480)/1000 in 2010-2014, (p = 0.009). Among all CHD conditions, atrial septal defects and ventricular septal defects chiefly accounted for this increasing trend. The summarised prevalence (1970-2017) of CHD diagnoses first made in childhood was 1.384 (0.955, 1.891)/1000; during this time there was a fall from 2.050 [1.362, 2.877]/1000 pre-1995 to 0.848 [0.626, 1.104]/1000 in 1995-2014 (p = 0.04). CONCLUSIONS: Globally, these data show an increased prevalence of CHD (mainly mild CHD conditions) recognised at birth/infancy or early childhood, but remaining unrepaired at school-age. In parallel there has been a decrease of first-time CHD diagnoses in school-age children. These together imply a favourable shift of CHD recognition time to earlier in the life course. Despite this, substantial inequalities between higher and lower income countries remain. Increased healthcare resources for people born with CHD, particularly in poorer countries, are required.

Machine learning algorithms estimating prognosis and guiding therapy in adult congenital heart disease: data from a single tertiary centre including 10 019 patients.

AIMS: To assess the utility of machine learning algorithms on estimating prognosis and guiding therapy in a large cohort of patients with adult congenital heart disease (ACHD) or pulmonary hypertension at a single, tertiary centre. METHODS AND RESULTS: We included 10 019 adult patients (age 36.3 ± 17.3 years) under follow-up at our institution between 2000 and 2018. Clinical and demographic data, ECG parameters, cardiopulmonary exercise testing, and selected laboratory markers where collected and included in deep learning (DL) algorithms. Specific DL-models were built based on raw data to categorize diagnostic group, disease complexity, and New York Heart Association (NYHA) class. In addition, models were developed to estimate need for discussion at multidisciplinary team (MDT) meetings and to gauge prognosis of individual patients. Overall, the DL-algorithms-based on over 44 000 medical records-categorized diagnosis, disease complexity, and NYHA class with an accuracy of 91.1%, 97.0%, and 90.6%, respectively in the test sample. Similarly, patient presentation at MDT-meetings was predicted with a test sample accuracy of 90.2%. During a median follow-up time of 8 years, 785 patients died. The automatically derived disease severity-score derived from clinical information was related to survival on Cox analysis independently of demographic, exercise, laboratory, and ECG parameters. CONCLUSION: We present herewith the utility of machine learning algorithms trained on large datasets to estimate prognosis and potentially to guide therapy in ACHD. Due to the largely automated process involved, these DL-algorithms can easily be scaled to multi-institutional datasets to further improve accuracy and ultimately serve as online based decision-making tools.

Preoperative Predictors of Death and Sustained Ventricular Tachycardia After Pulmonary Valve Replacement in Patients With Repaired Tetralogy of Fallot Enrolled in the INDICATOR Cohort.

BACKGROUND: Risk factors for adverse clinical outcomes have been identified in patients with repaired tetralogy of Fallot before pulmonary valve replacement (PVR). However, pre-PVR predictors for post-PVR sustained ventricular tachycardia and death have not been identified. METHODS: Patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort (International Multicenter TOF Registry), a 4-center international cohort study, who had a comprehensive preoperative evaluation and subsequently underwent PVR were included. Preprocedural clinical, ECG, cardiovascular magnetic resonance, and postoperative outcome data were analyzed. Cox proportional hazards multivariable regression analysis was used to evaluate factors associated with time from pre-PVR cardiovascular magnetic resonance until the primary outcome: death, aborted sudden cardiac death, or sustained ventricular tachycardia. RESULTS: Of the 452 eligible patients (median age at PVR, 25.8 years), 36 (8%) reached the primary outcome (27 deaths, 2 resuscitated death, and 7 sustained ventricular tachycardia) at a median time after PVR of 6.5 years. Cox proportional hazards regression identified pre-PVR right ventricular ejection fraction <40% (hazard ratio, 2.39; 95% CI, 1.18-4.85; P=0.02), right ventricular mass-to-volume ratio ≥0.45 g/mL (hazard ratio, 4.08; 95% CI, 1.57-10.6; P=0.004), and age at PVR ≥28 years (hazard ratio, 3.10; 95% CI, 1.42-6.78; P=0.005) as outcome predictors. In a subgroup analysis of 230 patients with Doppler data, predicted right ventricular systolic pressure ≥40 mm Hg was associated with the primary outcome (hazard ratio, 3.42; 95% CI, 1.09-10.7; P=0.04). Preoperative predictors of a composite secondary outcome, postoperative arrhythmias and heart failure, included older age at PVR, pre-PVR atrial tachyarrhythmias, and a higher left ventricular end-systolic volume index. CONCLUSIONS: In this observational investigation of patients with repaired tetralogy of Fallot, an older age at PVR and pre-PVR right ventricular hypertrophy and dysfunction were predictive of a shorter time to postoperative death and sustained ventricular tachycardia. These findings may inform the timing of PVR if confirmed by prospective clinical trials.

Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study.

BACKGROUND: Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot provides symptomatic benefit and right ventricular (RV) volume reduction. However, data on the rate of ventricular structural and functional adaptation are scarce. We aimed to assess immediate and midterm post-PVR changes and predictors of reverse remoeling. METHODS: Fifty-seven patients with repaired tetralogy of Fallot (age ≥16 y; mean age, 35.8±10.1 y; 38 male) undergoing PVR were prospectively recruited for cardiovascular magnetic resonance performed before PVR (pPVR), immediately after PVR (median, 6 d), and midterm after PVR (mPVR; median, 3 y). RESULTS: There were immediate and midterm reductions in indexed RV end-diastolic volumes and RV end-systolic volumes (RVESVi) (indexed RV end-diastolic volume pPVR versus immediately after PVR versus mPVR, 156.1±41.9 versus 104.9±28.4 versus 104.2±34.4 mL/m2; RVESVi pPVR versus immediately after PVR versus mPVR, 74.9±26.2 versus 57.4±22.7 versus 50.5±21.7 mL/m2; P<0.01). Normal postoperative diastolic and systolic RV volumes (the primary end point) achieved in 70% of patients were predicted by a preoperative indexed RV end-diastolic volume ≤158 mL/m2 and RVESVi ≤82 mL/m2. RVESVi showed a progressive decrease from baseline to immediate to midterm follow-up, indicating ongoing intrinsic RV functional improvement after PVR. Left ventricular ejection fraction improved (pPVR versus mPVR, 59.4±7.6% versus 61.9±6.8%; P<0.01), and right atrial reverse remodeling occurred (pPVR versus mPVR, 15.2±3.4 versus 13.8±3.6 cm2/m2; P<0.01). Larger preoperative RV outflow tract scar was associated with a smaller improvement in post-PVR RV/left ventricular ejection fraction. RV ejection fraction and peak oxygen uptake predicted mortality (P=0.03) over a median of 9.5 years of follow-up. CONCLUSIONS: Significant right heart structural reverse remodeling takes place immediately after PVR, followed by a continuing process of further biological remodeling manifested by further reduction in RVESVi. PVR before RVESVi reaches 82 mL/m2 confers optimal chances of normalization of RV function.

Imaging of congenital heart disease in adults.

Imaging is fundamental to the lifelong care of adult congenital heart disease (ACHD) patients. Echocardiography remains the first line imaging for inpatient, outpatient, or perioperative care. Cross-sectional imaging with cardiovascular magnetic resonance (CMR) or computed tomography (CT) provides complementary and invaluable information on cardiac and vascular anatomy and other intra-thoracic structures. Furthermore, CMR provides quantification of cardiac function and vascular flow. Cardiac catheterization is mostly reserved for assessment of pulmonary vascular resistance, ventricular end-diastolic pressure, and percutaneous interventions. There have been further advances in non-invasive imaging for ACHD including the application of advanced echocardiographic techniques, faster automated CMR imaging, and radiation dose reduction in CT. As a result ACHD, a heterogeneous population, benefit from appropriate application of multiple imaging modalities matched with tertiary ACHD expertise.

Depression requiring anti-depressant drug therapy in adult congenital heart disease: prevalence, risk factors, and prognostic value.

BACKGROUND: Depression is prevalent in adults with congenital heart disease (ACHD), but limited data on the frequency of anti-depressant drug (ADD) therapy and its impact on outcome are available. METHODS AND RESULTS: We identified all ACHD patients treated with ADDs between 2000 and 2011 at our centre. Of 6162 patients under follow-up, 204 (3.3%) patients were on ADD therapy. The majority of patients were treated with selective serotonin-reuptake inhibitors (67.4%), while only 17.0% of patients received tricyclic anti-depressants. Twice as many female patients used ADDs compared with males (4.4 vs. 2.2%, P < 0.0001). The percentage of patients on ADDs increased with disease complexity (P < 0.0001) and patient age (P < 0.0001). Over a median follow-up of 11.1 years, 507 (8.2%) patients died. After propensity score matching, ADD use was found to be significantly associated with worse outcome in male ACHD patients [hazard ratio 1.44 (95% confidence interval 1.17-1.84)]. There was no evidence that this excess mortality was directly related to ADD therapy, QT-prolongation, or malignant arrhythmias. However, males taking ADDs were also more likely to miss scheduled follow-up appointments compared with untreated counterparts, while no such difference in clinic attendance was seen in females. CONCLUSIONS: The use of ADD therapy in ACHD relates to gender, age, and disease complexity. Although, twice as many female patients were on ADDs, it were their male counterparts, who were at increased mortality risk on therapy. Furthermore, males on ADDs had worse adherence to scheduled appointments suggesting the need for special medical attention and possibly psychosocial intervention for this group of patients.

Fatal severe coronary artery stenosis in Williams syndrome: decision making using late gadolinium enhancement cardiovascular MRI.

Williams syndrome is a well-recognised congenital disorder characterised by cardiovascular, connective tissue, and central nervous system abnormalities. Coronary artery abnormalities are seen in patients with supravalvar aortic stenosis, but end-stage ischaemic heart disease is rare. We report a case of end-stage ischaemic heart disease due to severe coronary arterial stenosis, highlighting how cardiovascular MRI contributed to the management.

Magnetic resonance imaging phantoms for quality-control of myocardial T1 and ECV mapping: specific formulation, long-term stability and variation with heart rate and temperature.

BACKGROUND: Magnetic resonance imaging (MRI) phantoms are routinely used for quality assurance in MRI centres; however their long term stability for verification of myocardial T1/ extracellular volume fraction (ECV) mapping has never been investigated. METHODS: Nickel-chloride agarose gel phantoms were formulated in a reproducible laboratory procedure to mimic blood and myocardial T1 and T2 values, native and late after Gadolinium administration as used in T1/ECV mapping. The phantoms were imaged weekly with an 11 heart beat MOLLI sequence for T1 and long TR spin-echo sequences for T2, in a carefully controlled reproducible manner for 12 months. RESULTS: There were only small relative changes seen in all the native and post gadolinium T1 values (up to 9.0 % maximal relative change in T1 values) or phantom ECV (up to 8.3 % maximal relative change of ECV, up to 2.2 % maximal absolute change in ECV) during this period. All native and post gadolinium T2 values remained stable over time with <2 % change. Temperature sensitivity testing showed MOLLI T1 values in the long T1 phantoms increasing by 23.9 ms per degree increase and short T1 phantoms increasing by 0.3 ms per degree increase. There was a small absolute increase in ECV of 0.069 % (~0.22 % relative increase in ECV) per degree increase. Variation in heart rate testing showed a 0.13 % absolute increase in ECV (~0.45 % relative increase in ECV) per 10 heart rate increase. CONCLUSIONS: These are the first phantoms reported in the literature modeling T1 and T2 values for blood and myocardium specifically for the T1mapping/ECV mapping application, with stability tested rigorously over a 12 month period. This work has significant implications for the utility of such phantoms in improving the accuracy of serial scans for myocardial tissue characterisation by T1 mapping methods and in multicentre work.

Clinical outcomes of surgical pulmonary valve replacement after repair of tetralogy of Fallot and potential prognostic value of preoperative cardiopulmonary exercise testing.

BACKGROUND: Indications for surgical pulmonary valve replacement (PVR) after repair of tetralogy of Fallot have recently been broadened to include asymptomatic patients. METHODS AND RESULTS: The outcomes of PVR in adults after repair of tetralogy of Fallot at a single tertiary center were retrospectively studied. Preoperative cardiopulmonary exercise testing was included. Mortality was the primary outcome measure. In total, 221 PVRs were performed in 220 patients (130 male patients; median age, 32 years; range, 16-64 years). Homografts were used in 117 patients, xenografts in 103 patients, and a mechanical valve in 1 patient. Early (30-day) mortality was 2%. Overall survival was 97% at 1 year, 96% at 3 years, and 92% at 10 years. Survival after PVR in the later era (2005-2010; n=156) was significantly better compared with survival in the earlier era (1993-2004; n=65; 99% versus 94% at 1 year and 98% versus 92% at 3 years, respectively; P=0.019). Earlier era patients were more symptomatic preoperatively (P=0.036) with a lower preoperative peak oxygen consumption (peak Vo2; P<0.001). Freedom from redo surgical or transcatheter PVR was 98% at 5 years and 96% at 10 years for the whole cohort. Peak Vo2, E/CO2 slope (ratio of minute ventilation to carbon dioxide production), and heart rate reserve during cardiopulmonary exercise testing predicted risk of early mortality when analyzed with logistic regression analysis; peak Vo2 emerged as the strongest predictor on multivariable analysis (odds ratio, 0.65 per 1 mL·kg⁻¹·min⁻¹; P=0.041). CONCLUSIONS: PVR after repair of tetralogy of Fallot has a low and improving mortality, with a low need for reintervention. Preoperative cardiopulmonary exercise testing predicts surgical outcome and should therefore be included in the routine assessment of these patients.

Dynamic inversion time for improved 3D late gadolinium enhancement imaging in patients with atrial fibrillation.

PURPOSE: High resolution three-dimensional (3D) late gadolinium enhancement (LGE) imaging is performed with single R-wave gating to minimize lengthy acquisition durations. In patients with atrial fibrillation (AF), heart rate variability results in variable magnetization recovery between sequence repeats, and image quality is often poor. In this study, we implemented and tested a dynamic inversion time (dynamic-TI) scheme designed to reduce sequence sensitivity to heart rate variations. METHODS: An inversion-prepared 3D segmented gradient echo sequence was modified so that the TI varied automatically from beat-to-beat (dynamic-TI) based on the time since the last sequence repeat. 3D LGE acquisitions were performed in 17 patients prior to radio frequency ablation of persistent AF both with and without dynamic-TI. Qualitative image quality scores, blood signal-to-ghosting ratios (SGRs). and blood-myocardium contrast-to-ghosting ratios (CGRs) were compared. RESULTS: Image quality scores were higher with dynamic-TI than without dynamic-TI (2.2 ± 0.9 vs. 1.8 ± 1.1, P = 0.008), as were blood-myocardium CGRs (13.8 ± 7.6 vs. 8.3 ± 6.1, P = 0.003) and blood SGRs (19.6 ± 8.5 vs. 13.1 ± 8.0, P = 0.003). CONCLUSION: The dynamic-TI algorithm improves image quality of 3D LGE imaging in this difficult patient population by reducing the sequence sensitivity to RR interval variations

Improved respiratory efficiency of 3D late gadolinium enhancement imaging using the continuously adaptive windowing strategy (CLAWS).

PURPOSE: Acquisition durations of navigator-gated high-resolution three-dimensional late gadolinium enhancement studies may typically be up to 10 min, depending on the respiratory efficiency and heart rate. Implementation of the continuously adaptive windowing strategy (CLAWS) could increase respiratory efficiency, but the resulting non-smooth k-space acquisition order during gadolinium wash-out could result in increased artifact. METHODS: Navigator-gated three-dimensional late gadolinium enhancement acquisitions were performed in 18 patients using tracking end-expiratory accept/reject (EE-ARA) and CLAWS algorithms in random order. RESULTS: Retrospective analysis of the stored navigator data shows that CLAWS scan times are very close to (within 1%) or equal to the fastest achievable scan times while EE-ARA significantly extends the acquisition duration (P < 0.0001). EE-ARA acquisitions are 26% longer than CLAWS acquisitions (378 ± 104 s compared to 301 ± 85 s, P = 0.002). Image quality scores for CLAWS and EE-ARA acquisitions are not significantly different (4.1 ± 0.6 compared to 4.3 ± 0.6, P = ns). Numerical phantom simulations show that the non-uniform k-space ordering introduced by CLAWS results in slight, but not statistically significant, reductions in both blood signal-to-noise ratio (10%) and blood-myocardium contrast-to-noise ratio (12%). CONCLUSIONS: CLAWS results in markedly reduced acquisition durations compared to EE-ARA without significant detriment to the image quality.

Myocardial fibrosis in Eisenmenger syndrome: a descriptive cohort study exploring associations of late gadolinium enhancement with clinical status and survival.

BACKGROUND: A relationship between myocardial fibrosis and ventricular dysfunction has been demonstrated using late gadolinium enhancement (LGE) in the pressure-loaded right ventricle from congenital heart defects. In patients with Eisenmenger syndrome (ES), the presence of LGE has not been investigated. The aims of this study were to detect any myocardial fibrosis in ES and describe major clinical variables associated with the finding. METHODS: From 45 subjects screened, 30 subjects (age 43 ± 13 years, 20 female) underwent prospective cardiovascular magnetic resonance with LGE to quantify biventricular volume and function as well as maximal and submaximal exercise during a single visit. Standard cine acquisitions were obtained for ventricular volume and function. Further imaging was performed after administration of 0.1 mmol/kg gadolinium contrast. Regions of LGE were evaluated qualitatively and quantitatively by manual contouring of identified areas, with total area expressed as a percentage of mass. Patients were followed prospectively (mean follow up 7.4 ± 0.4 years) and any deaths recorded. Patients with LGE findings were compared to those without. RESULTS: LGE was present in 22/30 (73%) patients, specifically in RV myocardium (70%), RV trabeculae (60%), LV myocardium (33%) or LV papillary muscles (30%), though in small amounts (mean 1.4% of total ventricular mass, range 0.16 - 6.0%). Those with any LGE were not different in age, history of arrhythmia, desaturation, nor hemoglobin, nor ventricular size, mass, or function. Exercise capacity was low, but also not different between those with and without LGE. Similarly no significant associations were found with amount of fibrosis. There were five deaths among patients with LGE, versus two in patients without, but no difference in survival (log rank =0.03, P = 0.85). CONCLUSIONS: Myocardial fibrosis by LGE is common in ES, though not extensive. The presence and quantity of LGE did not correlate with ventricular size, function, degree of cyanosis, exercise capacity, or survival in this pilot study. More data are clearly required before recommendations for routine use of LGE in these patients can be made.

Development and Validation of a Mortality Risk Score for Repaired Tetralogy of Fallot.

BACKGROUND: Robust risk assessment is crucial for the growing repaired tetralogy of Fallot population at risk of major adverse clinical outcomes; however, current tools are hindered by lack of validation. This study aims to develop and validate a risk prediction model for death in the repaired tetralogy of Fallot population. METHODS AND RESULTS: Patients with repaired tetralogy of Fallot enrolled in the INDICATOR (International Multicenter Tetralogy of Fallot Registry) cohort with clinical, arrhythmia, cardiac magnetic resonance, and outcome data were included. Patients from London, Amsterdam, and Boston sites were placed in the development cohort; patients from the Toronto site were used for external validation. Multivariable Cox regression was used to evaluate factors associated with time from cardiac magnetic resonance until the primary outcome: all-cause death. Of 1552 eligible patients (n=1221 in development, n=331 in validation; median age at cardiac magnetic resonance 23.4 [interquartile range, 15.6-35.6] years; median follow up 9.5 years), 102 (6.6%) experienced the primary outcome. The multivariable Cox model performed similarly during development (concordance index, 0.83 [95% CI, 0.78-0.88]) and external validation (concordance index, 0.80 [95% CI, 0.71-0.90]) and identified older age at cardiac magnetic resonance, obesity, type of tetralogy of Fallot repair, higher right ventricular end-systolic volume index, and lower biventricular global function index as independent predictors of death. A risk-scoring algorithm dividing patients into low-risk (score ≤4) versus high-risk (score >4) groups was validated to effectively discriminate risk of death (15-year survival of 95% versus 74%, respectively; P<0.001). CONCLUSIONS: This externally validated mortality risk prediction algorithm can help identify vulnerable patients with repaired tetralogy of Fallot who may benefit from targeted interventions.

Magnetic navigation in adults with atrial isomerism (heterotaxy syndrome) and supraventricular arrhythmias.

AIMS: We analysed the type and mechanism of supraventricular arrhythmias encountered in a series of symptomatic adults with atrial isomerism undergoing catheter ablation procedures. METHODS AND RESULTS: The study population included consecutive adults with atrial isomerism who had previously undergone surgical repair or palliation of the associated anomalies. Patients underwent electrophysiological study for symptomatic arrhythmia in our institution between 2010 and 2012 using magnetic navigation in conjunction with CARTO RMT and three-dimensional (3D) image integration. Eight patients (five females) with a median age of 33 years [interquartile range (IQR) 24-39] were studied. Access to the cardiac chambers of interest was obtained retrogradely via the aorta using remotely navigated magnetic catheters in six patients. Radiofrequency ablation successfully targeted twin atrioventricular (AV) nodal reentrant tachycardia in two patients, atrial fibrillation (AF) in three, focal atrial tachycardia (AT) mainly originating in the left-sided atrium in four patients, and macro-reentrant AT dependent on a right-sided inferior isthmus in three patients. The median fluoroscopy time was 3.0 min (IQR 2-11). After a median follow-up of 10 months (IQR 6-21), five of the ablated patients are free from arrhythmia; two patients experienced episodes of self-terminated AF and AT, respectively, within one month post-ablation; the remaining patient had only non-sustained AT during the electrophysiological study and was managed medically. CONCLUSION: Various supraventricular tachycardia mechanisms are possible in adults with heterotaxy syndrome, all potentially amenable to radiofrequency ablation. The use of remote magnetic navigation along with 3D mapping facilitated the procedures and resulted in a short radiation time.

Rationale and design of an International Multicenter Registry of patients with repaired tetralogy of Fallot to define risk factors for late adverse outcomes: the INDICATOR cohort.

Although early survival after tetralogy of Fallot (TOF) repair in the modern era is excellent, studies on late outcomes have shown increasing rates of mortality and morbidity. Despite multiple publications on factors associated with late complications, risk factors for major outcomes (death and sustained ventricular tachycardia [VT]) remain poorly defined. Consequently, the International Multicenter TOF Registry (INDICATOR) was established. This article describes the development, structure, and goals of this registry and characterizes the initial cohort derived from four large congenital heart centers in the United States, Canada, and Europe. A data coordinating center with a core cardiac magnetic resonance (CMR) laboratory and statistical core was established. Subjects with repaired TOF who had CMR imaging performed between 1997 and 2010 and ≥ 1 year follow-up were included. Clinical end points were death and sustained VT. Demographic, electrophysiologic, exercise, and outcome data were collected. A total of 873 subjects fulfilled inclusion criteria (median age at repair 2.9 years and at CMR imaging 22.8 years). Of these, 9 % had QRS duration >180 ms on electrocardiogram (ECG). On CMR imaging, 38 % had severe right-ventricular (RV) dilatation (≥ 160 mL/m(2)), and 6 % had severe RV dysfunction (ejection fraction < 35 %). Of the 551 subjects with exercise testing available, 28 % had severely decreased exercise capacity with <50 % predicted peak oxygen consumption. The INDICATOR cohort allows robust statistical analysis to evaluate major clinical outcomes in patients with repaired TOF. Continued follow-up and further expansion of the registry may provide new insights into innovative therapeutic strategies to improve late outcomes.

Use of Cardiovascular Magnetic Resonance for Risk Stratification in Repaired Tetralogy of Fallot.

The risk of premature death in adult patients with repaired tetralogy of Fallot is real and not inconsiderable. From the third decade of life, the incidence of malignant ventricular arrhythmia (VA) is known to exponentially rise. Progressive adverse mechanoelectrical modelling because of years of volume and/or pressure overload from residual pulmonary valve dysfunction and ventricular scar creates the perfect catalyst for VA. Although potentially lifesaving, implantable cardiac defibrillators are associated with substantial psychological and physical morbidity. Better selection of patients most at risk of VA, so that implantable cardiac defibrillators are not inflicted on patients who will never need them, is therefore crucial and has inspired research on this topic for several decades. Cardiovascular magnetic resonance (CMR) enables noninvasive, radiation-free clinical assessment of anatomy and function, making it ideal for the lifelong surveillance of patients with congenital heart disease. Gold standard measurements of ventricular volumes and systolic function can be derived from CMR. Tissue characterization using CMR can identify a VA substrate and provides insight into myocardial disease. We detail risk factors for VA identified using currently available CMR techniques. We also discuss emerging and advanced CMR techniques that have not all yet translated into routine clinical practice. We review how CMR-defined predictors of VA in repaired tetralogy of Fallot can be incorporated into risk scores with other clinical factors to improve the accuracy of risk prediction and to allow for pragmatic clinical application. Finally, we discuss what the future may hold.

Le risque de décès prématuré chez les patients adultes présentant une tétralogie de Fallot réparée (TFr) est bien réel et doit être pris en considération. À partir de la trentaine, l'incidence de l'arythmie ventriculaire (AV) maligne augmente exponentiellement chez ces patients. Le remodelage mécanoélectrique défavorable causé sur de nombreuses années par une surcharge de volume ou de pression liée à la dysfonction de la valve pulmonaire et à la cicatrice ventriculaire constitue un catalyseur de l'AV. Les défibrillateurs implantables peuvent sauver la vie des patients, mais ils sont également associés à des taux de morbidité psychologique et physique importants. Il est donc crucial de mieux cerner les patients les plus susceptibles de présenter une AV pour éviter d'implanter un défibrillateur à ceux qui n'en auront jamais besoin. Plusieurs études ont d'ailleurs porté sur cette question au cours des dernières décennies. La résonance magnétique cardiovasculaire (RMC) permet une évaluation clinique non invasive et sans radiation de l'anatomie et la physiologie, ce qui en fait une technique idéale pour la surveillance à vie des patients atteints de cardiopathies congénitales. Des mesures de référence du volume ventriculaire et de la fonction systolique peuvent être obtenues par RMC. La caractérisation des tissus par RMC peut permettre de repérer le substrat de l'AV et de renseigner sur la maladie myocardique. Nous décrivons les facteurs de risque de l'AV pouvant être repérés par les techniques de RMC actuelles, et nous présentons des techniques de pointe et en émergence qui n'ont pas encore trouvé leur place dans la pratique clinique courante. Nous examinons la façon dont les facteurs de prédiction de l'AV définis par RMC chez les patients atteints de TFr peuvent être intégrés aux indices de risque et conjugués à d'autres facteurs cliniques pour améliorer l'exactitude des prédictions et connaître une application clinique pratique. Nous évoquons enfin les possibilités futures.