Improved Outcomes After Pulmonary Valve Replacement in Repaired Tetralogy of Fallot.

BACKGROUND: The impact of pulmonary valve replacement (PVR) on major adverse clinical outcomes in patients with repaired tetralogy of Fallot (rTOF) is unknown. OBJECTIVES: The purpose of this study was to determine whether PVR is associated with improved survival and freedom from sustained ventricular tachycardia (VT) in rTOF. METHODS: A PVR propensity score was created to adjust for baseline differences between PVR and non-PVR patients enrolled in INDICATOR (International Multicenter TOF Registry). The primary outcome was time to the earliest occurrence of death or sustained VT. PVR and non-PVR patients were matched 1:1 on PVR propensity score (matched cohort) and in the full cohort, modeling was performed with propensity score as a covariate adjustment. RESULTS: Among 1,143 patients with rTOF (age 27 ± 14 years, 47% PVR, follow-up 8.3 ± 5.2 years), the primary outcome occurred in 82. The adjusted HR for the primary outcome for PVR vs no-PVR (matched cohort n = 524) was 0.41 (95% CI: 0.21-0.81; multivariable model P = 0.010). Full cohort analysis revealed similar results. Subgroup analysis suggested beneficial effects in patients with advanced right ventricular (RV) dilatation (interaction P = 0.046; full cohort). In patients with RV end-systolic volume index >80 mL/m2, PVR was associated with a lower primary outcome risk (HR: 0.32; 95% CI: 0.16-0.62; P < 0.001). There was no association between PVR and the primary outcome in patients with RV end-systolic volume index ≤80 mL/m2 (HR: 0.86; 95% CI: 0.38-1.92; P = 0.70). CONCLUSIONS: Compared with rTOF patients who did not receive PVR, propensity score-matched individuals receiving PVR had lower risk of a composite endpoint of death or sustained VT.

A comparison of ECG-based home monitoring devices in adults with CHD.

BACKGROUND: Various electrocardiogram (ECG)-based devices are available for home monitoring, but the reliability in adults with CHD is unknown. Therefore, we determined the accuracy of different ECG-based devices compared to the standard 12-lead ECG in adult CHD. METHODS AND RESULTS: This is a single-centre, prospective, cross-sectional study in 176 consecutive adults with CHD (54% male, age 40 ± 16.6 years, 24% severe CHD, 84% previous surgery, 3% atrial fibrillation (AF), 24% right bundle branch block). Diagnostic accuracy of the Withings Scanwatch (lead I), Eko DUO (precordial lead), and Kardia 6L (six leads) was determined in comparison to the standard 12-lead ECG on several tasks: 1) AF classification (percentage correct), 2) QRS-morphology classification (percentage correct), and 3) ECG intervals calculation (QTc time ≤ 40 ms difference). Both tested AF algorithms had high accuracy (Withings: 100%, Kardia 6L: 97%) in ECGs that were classified. However, the Withings algorithm classified fewer ECGs as inconclusive (5%) compared to 31% of Kardia (p < 0.001). Physician evaluation of Kardia correctly classified QRS morphology more frequently (90% accuracy) compared to Eko DUO (84% accuracy) (p = 0.03). QTc was underestimated on all ECG-based devices (p < 0.01). QTc duration accuracy was acceptable in only 51% of Withings versus 70% Eko and 74% Kardia (p < 0.001 for both comparisons). CONCLUSIONS: Although all devices demonstrated high accuracy in AF detection, the Withings automatic algorithm had fewest uninterpretable results. Kardia 6L was most accurate in overall evaluation such as QRS morphology and QTc duration. These findings can inform both patients and caregivers for optimal choice of home monitoring.

Six-lead device superior to single-lead smartwatch ECG in atrial fibrillation detection.

This was a head-to-head comparative study on different electrocardiogram (ECG)-based smartwatches and devices for atrial fibrillation detection. We prospectively included 220 patients scheduled for electrical cardioversion and recorded ECGs with 3 different devices (Withings Move ECG, Apple Watch 5, Kardia Mobile 6-leads) as well as the standard 12-lead ECG (gold standard), both before and after cardioversion. All atrial fibrillation detection algorithms had high accuracy (sensitivity and specificity: 91-99%) but were hampered by uninterpretable recordings (20-24%). In cardiologists' interpretation, the 6-lead device was superior (sensitivity 99%, specificity 97%) to both single-lead smartwatches (P < .05) for atrial fibrillation detection.

Risk Factors for Mortality and Ventricular Tachycardia in Patients With Repaired Tetralogy of Fallot: A Systematic Review and Meta-analysis.

BACKGROUND: Patients with repaired tetralogy of Fallot (rTOF) have increased risk for mortality, sudden cardiac death, and ventricular tachycardia (VT). The aim of this systematic review and meta-analysis is to offer an updated analysis of risk factors following significant changes in surgical and perioperative management. METHODS: A meta-analysis based on the published literature between 2008 and 2018 was conducted. Endpoints were VT, cardiac mortality/VT, and all-cause mortality/VT. Studies with ≥100 patients and ≥10 events were included. RESULTS: Fifteen studies including 7218 patients (average age 27.5 years) were analyzed. Risk factors for VT included older age (per 1 year, odds ratio [OR]: 1.039; 95% confidence interval [CI]: 1.025-1.053), older age at corrective surgery (per 1 year, OR: 1.034; CI: 1.017-1.051), previous palliative shunt (OR: 3.063; CI: 1.525-6.151), number of thoracotomies (OR: 1.416; CI: 1.249-1.604), longer QRS duration (per 1 ms, OR: 1.031; CI: 1.008-1.055), and at least moderate right-ventricular dysfunction (OR: 2.160; CI_ 1.311-3.560). Additional risk factors for cardiac death/VT were previous ventriculotomy (OR: 2.269; CI: 1.226-4.198), lower left-ventricular ejection fraction (per 1%, OR: 1.049; CI: 1.029-1.071), and higher right-ventricular end diastolic volume (per 1 mL/m2, OR: 1.009; CI: 1.002-1.016). Supraventricular tachycardia/atrial fibrillation was an additional risk factor for all-cause mortality/VT (OR: 1.939; CI: 1.088-3.457). CONCLUSIONS: The study highlights the importance of preservation of biventricular systolic function on late outcomes. Ventricular function appears to have a greater impact on outcomes than the severity of pulmonary regurgitation alone in this patient population.

Risk of coronary artery disease in adults with congenital heart disease: A comparison with the general population.

BACKGROUND: Coronary artery disease (CAD) will increasingly determine outcome in the aging adult congenital heart disease (CHD) population. We aimed to determine sex-specific incidence of CAD in adult CHD patients throughout adulthood, compared to the general population. METHODS AND RESULTS: We followed 11,723 adult CHD patients (median age 33 years; 49% male; 57% mild, 34% moderate, 9% severe CHD) from the Dutch CONCOR registry, and two age-sex-matched persons per patient from the general population for first CAD event in national registers (period 2002-2012). Incidence rates were estimated using smoothed hazard functions. CAD risk during follow-up, stratified by CHD severity, was compared using proportional subdistribution hazards regression. In ACHD patients, 103 CAD events (43 women) occurred over 60,456 person-years. Rates per 1000person-years increased from 0.3(95% confidence interval: 0.1-0.6) at age 20 to 5.8(3.7-8.9) at 70 years in female, and from 0.5(0.3-1.0) to 7.8(5.1-11.8) in male patients. Compared to the general population, relative risk was 12.0(2.5-56.3) in women and 4.6(1.7-12.1) in men aged 20 years. Relative risk declined with age, remaining significant up to age ~65 years in women and ~50 years in men. In patients with mild, moderate and severe CHD, CAD risk was 1.3(0.9-1.9), 1.6(1.0-2.5) and 2.9(1.3-6.9) times increased compared to the general population, respectively. CONCLUSIONS: We found increased CAD risk in adult CHD patients, with greater relative risk at younger age, in women and those with more severe CHD. These results underline the importance of screening for and treatment of CAD risk factors in these patients.

Learning strategies among adult CHD fellows.

OBJECTIVE: Subspecialisation is increasingly a fundamental part of the contemporary practice of medicine. However, little is known about how medical trainees learn in the modern era, and particularly in growing and relatively new subspecialties, such as adult CHD. The purpose of this study was to assess institutional-led and self-directed learning strategies of adult CHD fellows. METHODS: This international, cross-sectional online survey was conducted by the International Society for Adult Congenital Heart Disease and consisted primarily of categorical questions and Likert rating scales. All current or recent (i.e., those within 2 years of training) fellows who reported training in adult CHD (within adult/paediatric cardiology training or within subspecialty fellowships) were eligible. RESULTS: A total of 75 fellows participated in the survey: mean age: 34 ± 5; 35 (47%) female. Most adult CHD subspecialty fellows considered case-based teaching (58%) as "very helpful", while topic-based teaching was considered "helpful" (67%); p = 0.003 (favouring case-based). When facing a non-urgent clinical dilemma, fellows reported that they were more likely to search for information online (58%) than consult a faculty member (29%) or textbook (3%). Many (69%) fellows use their smartphones at least once daily to search for information during regular clinical work. CONCLUSIONS: Fellows receiving adult CHD training reported a preference for case-based learning and frequent use of online material and smartphones. These findings may be incorporated into the design and enhancement of fellowships and development of online training resources.

Factors associated with coronary artery disease and stroke in adults with congenital heart disease.

OBJECTIVE: To determine factors associated with coronary artery disease (CAD) and ischaemic stroke in ageing adult congenital heart disease (ACHD) patients. METHODS: We performed a multicentre case-control study, using data from the national CONgenital CORvitia (CONCOR) registry to identify ACHD patients within five participating centres. Patients with CAD were matched (1:2 ratio) with ACHD patients without CAD on age, CHD defect group and gender. Patients with ischaemic stroke (or transient ischaemic attack) were matched similarly. Medical charts were reviewed and a standardised questionnaire was used to determine presence of risk factors. RESULTS: Of 6904 ACHD patients, a total of 55 cases with CAD (80% male, mean age 55.1±12.4 years) and 56 cases with stroke (46% male, mean age 46.9±15.2) were included and matched with control patients. In multivariable logistic regression analysis, traditional atherosclerotic risk factors (hypertension (OR 2.45; 95% CI 1.15 to 5.23), hypercholesterolaemia (OR 3.99; 95% CI 1.62 to 9.83) and smoking (OR 2.25; 95% CI 1.09 to 4.66)) were associated with CAD. In contrast, these risk factors were not associated with ischaemic stroke. In multivariable analysis, stroke was associated with previous shunt operations (OR 4.20; 95% CI 1.36 to 12.9), residual/unclosed septal defects (OR 2.38; 95% CI 1.03 to 5.51) and left-sided mechanical valves (OR 2.67; 95% CI 1.09 to 6.50). CONCLUSIONS: Traditional atherosclerotic risk factors were associated with CAD in ACHD patients. In contrast, ischaemic stroke was related to factors (previous shunts, septal defects, mechanical valves) suggesting a cardioembolic aetiology. These findings may inform surveillance and prevention strategies.

A propensity score-adjusted analysis of clinical outcomes after pulmonary valve replacement in tetralogy of Fallot.

OBJECTIVE: To determine the association of pulmonary valve replacement (PVR) with death and sustained ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot (rTOF). METHODS: Subjects with rTOF and cardiac magnetic resonance from an international registry were included. A PVR propensity score was created to adjust for baseline differences. PVR consensus criteria were predefined as pulmonary regurgitation >25% and ≥2 of the following criteria: right ventricular (RV) end-diastolic volume >160 mL/m2, RV end-systolic volume >80 mL/m2, RV ejection fraction (EF) <47%, left ventricular EF <55% and QRS duration >160 ms. The primary outcome included (aborted) death and sustained VT. The secondary outcome included heart failure, non-sustained VT and sustained supraventricular tachycardia. RESULTS: In 977 rTOF subjects (age 26±15 years, 45% PVR, follow-up 5.3±3.1 years), the primary and secondary outcomes occurred in 41 and 88 subjects, respectively. The HR for subjects with versus without PVR (time-varying covariate) was 0.65 (95% CI 0.31 to 1.36; P=0.25) for the primary outcome and 1.43 (95% CI 0.83 to 2.46; P=0.19) for the secondary outcome after adjusting for propensity and other factors. In subjects (n=426) not meeting consensus criteria, the HR for subjects with (n=132) versus without (n=294) PVR was 2.53 (95% CI 0.79 to 8.06; P=0.12) for the primary outcome and 2.31 (95% CI 1.07 to 4.97; P=0.03) for the secondary outcome. CONCLUSION: In this large multicentre rTOF cohort, PVR was not associated with a reduced rate of death and sustained VT at an average follow-up of 5.3 years. Additionally, there were more events after PVR compared with no PVR in subjects not meeting consensus criteria.

Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot.

BACKGROUND: The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. METHODS: The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] <50%) but without severe valvular dysfunction were eligible. Patients were randomly assigned between losartan (150 mg daily) and placebo with target treatment duration between 18 and 24 months. The primary outcome was RV EF change, determined by cardiovascular MRI in intention-to-treat analysis. RESULTS: Of 95 included patients, 47 patients received 150 mg losartan daily (age, 38.0±12.4 years; 74% male), and 48 patients received placebo (age, 40.6±11.4 years; 63% male). Overall, RV EF did not change in patients allocated to losartan (n=42) (44.4±5.1% to 45.2±5.0%) and placebo (n=46) (43.2±6.3% to 43.6±6.9%). Losartan did not significantly improve RV EF in comparison with placebo (+0.51%; 95% confidence interval, -1.0 to +2.0; P=0.50). No significant treatment effects were found on secondary outcomes: left ventricular EF, peak aerobic exercise capacity, and N-terminal pro-brain natriuretic peptide (P>0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EF<40%, pulmonary valve replacement, or QRS fragmentation. However, in a post hoc analysis, losartan was associated with improved RV EF in a subgroup (n=30) with nonrestrictive RV and incomplete remodeling (QRS fragmentation and previous pulmonary valve replacement) (+2.7%; 95% confidence interval, +0.1 to +5.4; P=0.045). CONCLUSIONS: Losartan had no significant effect on RV dysfunction or secondary outcome parameters in repaired tetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905.

Sudden cardiac death in adults with congenital heart disease: does QRS-complex fragmentation discriminate in structurally abnormal hearts?

Aims: Sudden cardiac death (SCD) causes a large portion of all mortality in adult congenital heart disease (ACHD) patients. However, identification of high-risk patients remains challenging. Fragmented QRS-complexes (fQRS) are a marker for SCD in patients with acquired heart disease but data in ACHD patients are lacking. We therefore aim to evaluate the prognostic value of fQRS for SCD in ACHD patients. Methods and results: From a multicentre cohort of 25 790 ACHD patients, we included tachyarrhythmic SCD cases (n = 147), and controls (n = 266) matched by age, gender, congenital defect and (surgical) intervention. fQRS was defined as ≥1 discontinuous deflection in narrow QRS-complexes, and ≥2 in wide QRS-complexes (>120 ms), in two contiguous ECG leads. We calculated odds ratios (OR) using univariable and multivariable conditional logistic regression models correcting for impaired systemic ventricular function, heart failure and QRS duration >120 ms. ECGs of 147 SCD cases (65% male, median age of death 34 years) and of 266 controls were assessed. fQRS was present in 51% of cases and 34% of controls (OR 2.0, P = 0.003). In multivariable analysis, fQRS was independently associated with SCD (OR 1.9, P = 0.01). The most common diagnose of SCD cases was tetralogy of Fallot (ToF, 34 cases). In ToF, fQRS was present in 71% of cases vs. 43% of controls (OR for SCD 2.8, P = 0.03). Conclusions: fQRS was independently associated with SCD in ACHD patients in a cohort of SCD patients and matched controls. fQRS may therefore contribute to the decision when evaluating ACHD patients for primary prevention of SCD.

Origins and consequences of congenital heart defects affecting the right ventricle.

Congenital heart disease is a major health issue, accounting for a third of all congenital defects. Improved early surgical management has led to a growing population of adults with congenital heart disease, including patients with defects affecting the right ventricle, which are often classified as severe. Defects affecting the right ventricle often cause right ventricular volume or pressure overload and affected patients are at high risk for complications such as heart failure and sudden death. Recent insights into the developmental mechanisms and distinct developmental origins of the left ventricle, right ventricle, and the outflow tract have shed light on the common features and distinct problems arising in specific defects. Here, we provide a comprehensive overview of the current knowledge on the development into the normal and congenitally malformed right heart and the clinical consequences of several congenital heart defects affecting the right ventricle.

Predicting long-term mortality after Fontan procedures: A risk score based on 6707 patients from 28 studies.

BACKGROUND: Reported long-term outcome measures vary greatly between studies in Fontan patients making comprehensive appraisal of mortality hazard challenging. We sought to create a clinical risk score to assist monitoring of Fontan patients in the outpatient setting. METHODS: A systematic review was conducted to evaluate risk factors for long-term (beyond the first postoperative year) mortality in Fontan patients. Studies were eligible for inclusion if ≥90 patients were included or ≥20 long-term mortalities we reported. Risk factors for long-term mortality were determined. The pooled hazard ratios were used to create components of a clinical score for long-term mortality using meta-analysis techniques. RESULTS: Twenty-eight studies were included. The total number of patients was 6707 with an average follow-up of 8.23 ± 5.42 years. There were 1000 deaths. Thirty-five risk factors for late mortality were identified and classified into 9 categories and their relative hazards were used to derive the initial components of a weighted, practical and clinically based Fontan risk score (ranging from 0 to 100). The final score included 8 risk factors: anatomic risk factors, elevated preoperative pulmonary artery pressure, atriopulmonary Fontan, heart failure symptoms, arrhythmia, moderate/severe ventricular dysfunction or atrioventricular valve regurgitation, protein losing enteropathy, and end organ disease (cirrhosis or renal insufficiency). CONCLUSION: In patients with Fontan circulation, the influence of readily available risk factors can be quantified in an integer score to predict long-term mortality. Prospective validation and refinement of this risk score will be undertaken.

Right vEntricular Dysfunction in tEtralogy of Fallot: INhibition of the rEnin-angiotensin-aldosterone system (REDEFINE) trial: Rationale and design of a randomized, double-blind, placebo-controlled clinical trial.

Renin-angiotensin-aldosterone system (RAAS) inhibition with angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors is beneficial in patients with acquired left ventricular dysfunction. Adult patients with tetralogy of Fallot (TOF) with right ventricular (RV) dysfunction are at high risk for heart failure, arrhythmias, and sudden cardiac death. However, the efficacy of RAAS inhibition has not been established in these patients. METHODS: The REDEFINE is an investigator-initiated, multicenter, prospective, randomized, double-blind, placebo-controlled trial to study the effects of the angiotensin II receptor blocker losartan (target dosage of 150 mg once daily) in adult patients with TOF. Patients with RV dysfunction in the absence of severe valvular dysfunction are eligible for inclusion. The primary end point is the change in RV ejection fraction after 18 to 24 months, as measured by cardiovascular magnetic resonance imaging. In addition, laboratory measurements, echocardiography, and cardiopulmonary exercise testing are performed. CONCLUSION: The REDEFINE trial will study the effects of RAAS inhibition with losartan in TOF patients with RV dysfunction.

Value of Cardiovascular Magnetic Resonance Imaging in Noninvasive Risk Stratification in Tetralogy of Fallot.

Importance: Adults late after total correction of tetralogy of Fallot (TOF) are at risk for major complications. Cardiovascular magnetic resonance (CMR) imaging is recommended to quantify right ventricular (RV) and left ventricular (LV) function. However, a commonly used risk model by Khairy et al requires invasive investigations and lacks CMR imaging to identify high-risk patients. Objective: To implement CMR imaging in noninvasive risk stratification to predict major adverse clinical outcomes. Design, Setting, and Participants: This multicenter study included 575 adult patients with TOF (4.083 patient-years at risk) from a prospective nationwide registry in whom CMR was performed. This study involved 5 tertiary referral centers with a specialized adult congenital heart disease unit. Multivariable Cox hazards regression analysis was performed to determine factors associated with the primary end point. The CMR variables were combined with the noninvasive components of the Khairy et al risk model, and the C statistic of the final noninvasive risk model was determined using bootstrap sampling. The data analysis was conducted from January to December 2016. Main Outcomes and Measures: The composite primary outcome was defined as all-cause mortality or ventricular arrhythmia, defined as aborted cardiac arrest or documented ventricular fibrillation and ventricular tachycardia (lasting ≥30 seconds or recurrent symptomatic). Results: Of the 575 patients with TOF, 57% were male, and the mean (SD) age was 31 (11) years. During a mean (SD) follow-up of 7.1 (3.5) years, the primary composite end point occurred in 35 patients, including all-cause mortality in 13 patients. Mean (SD) RV ejection fraction (EF) was 44% (10%), and mean (SD) LV EF was 53% (8%). There was a correlation between RV EF and LV EF (R, 0.36; 95% CI, 0.29-0.44; P < .001). Optimal thresholds for ventricular function (RV EF <30%: hazard ratio, 3.90; 95% CI, 1.84-8.26; P < .001 and LV EF <45%: hazard ratio, 3.23; 95% CI, 1.57-6.65; P = .001) were independently predictive in multivariable analysis. Both thresholds were included in a point-based noninvasive risk model (C statistic, 0.75; 95% CI, 0.63-0.85) and combined with the noninvasive components of the Khairy et al risk model. Conclusions and Relevance: In patients with repaired TOF, biventricular dysfunction on CMR imaging was associated with major adverse clinical outcomes. The quantified thresholds (RV EF <30% and LV EF <45%) may be implemented in noninvasive risk stratification.

Factors associated with long-term mortality after Fontan procedures: a systematic review.

BACKGROUND: Despite an ageing Fontan population, data on late outcomes are still scarce. Reported outcome measures and determinants vary greatly between studies making comprehensive appraisal of mortality hazard challenging. METHODS: We conducted a systematic review to evaluate causes and factors associated with late mortality in patients with Fontan circulation. Late mortality was defined as mortality beyond the first postoperative year. Studies were included if they had ≥90 patients or ≥20 late mortalities and/or transplants. Studies with overlapping patients were rationalised to include only the most recent studies to avoid duplication. RESULTS: From 28 studies, a total of 6707 patients with an average follow-up time of 8.23±5.42 years was identified. There were 1000 deaths. Causes of late death were reported in 697 cases. The five most common causes were heart/Fontan failure (22%), arrhythmia (16%), respiratory failure (15%), renal disease (12%) and thrombosis/bleeding (10%). Factors associated with late mortality were evaluated and classified into 9 categories. CONCLUSIONS: Causes and factors associated with late mortality after the Fontan operation are summarised in this study. The presented information will aid in identifying patients at highest risk for mortality and guide our risk stratification efforts in this patient population.

QRS fragmentation is superior to QRS duration in predicting mortality in adults with tetralogy of Fallot.

BACKGROUND: Although QRS duration >180 ms has prognostic value in adults with tetralogy of Fallot (TOF), its sensitivity to predict mortality is low. Fragmented QRS complexes, a simple measurement on ECG, are related to myocardial fibrosis and dysfunction in patients with TOF. Our objective was to determine whether QRS fragmentation predicts major outcomes in TOF. METHODS: This multicentre study included adult patients with TOF from a prospective registry. Notches in the QRS complex in ≥2 contiguous leads on a 12-lead ECG, not related to bundle branch block, were defined as QRS fragmentation, which was classified as none, moderate (≤4 leads) or severe (≥5 leads). The primary and secondary outcomes were all-cause mortality and clinical ventricular arrhythmia, respectively. RESULTS: A total of 794 adult patients with TOF (median age 27 years, 55% male; 52% no QRS fragmentation, 32% moderate, 16% severe) were included. During long-term (median 10.4 years) follow-up, 46 (6%) patients died and 35 (4%) patients had ventricular arrhythmias. Overall, 10-year survival was 98% in patients without fragmented QRS complexes, 93% in patients with moderate QRS fragmentation and 81% in patients with severe QRS fragmentation. In multivariable Cox hazards regression analysis, extent of QRS fragmentation (HR: 2.24/class, 95% CI 1.48 to 3.40, p<0.001) remained independently predictive for mortality, whereas QRS duration was not predictive (p=0.85). The extent of QRS fragmentation was also independently predictive for ventricular arrhythmia (HR: 2.00/class, 95% CI 1.26 to 3.16, p=0.003). CONCLUSIONS: The extent of QRS fragmentation is superior to QRS duration in predicting mortality in adult patients with TOF and may be used in risk stratification.