Background and AimsPatients with repaired tetralogy of Fallot remain at risk of life-threatening ventricular tachycardia related to slow-conducting anatomical isthmuses (SCAIs). Preventive ablation... Show moreBackground and AimsPatients with repaired tetralogy of Fallot remain at risk of life-threatening ventricular tachycardia related to slow-conducting anatomical isthmuses (SCAIs). Preventive ablation of SCAI identified by invasive electroanatomical mapping is increasingly performed. This study aimed to non-invasively identify SCAI using 3D late gadolinium enhancement cardiac magnetic resonance (3D-LGE-CMR).MethodsConsecutive tetralogy of Fallot patients who underwent right ventricular electroanatomical mapping (RV-EAM) and 3D-LGE-CMR were included. High signal intensity threshold for abnormal myocardium was determined based on direct comparison of bipolar voltages and signal intensity by co-registration of RV-EAM with 3D-LGE-CMR. The diagnostic performance of 3D-LGE-CMR to non-invasively identify SCAI was determined, validated in a second cohort, and compared with the discriminative ability of proposed risk scores.ResultsThe derivation cohort consisted of 48 (34 ± 16 years) and the validation cohort of 53 patients (36 ± 18 years). In the derivation cohort, 78 of 107 anatomical isthmuses (AIs) identified by EAM were normal-conducting AI, 22 were SCAI, and 7 blocked AI. High signal intensity threshold was 42% of the maximal signal intensity. The sensitivity and specificity of 3D-LGE-CMR for identifying SCAI or blocked AI were 100% and 90%, respectively. In the validation cohort, 85 of 124 AIs were normal-conducting AI, 36 were SCAI, and 3 blocked AI. The sensitivity and specificity of 3D-LGE-CMR were 95% and 91%, respectively. All risk scores showed an at best modest performance to identify SCAI (area under the curve ≤ .68).Conclusions3D late gadolinium enhancement cardiac magnetic resonance can identify SCAI with excellent accuracy and may refine non-invasive risk stratification and patient selection for invasive EAM in tetralogy of Fallot. Show less
AimsPatients with repaired tetralogy of Fallot (rTOF) have an increased risk of ventricular tachycardia (VT), with slow conducting anatomical isthmus (SCAI) 3 as dominant VT substrate. In patients... Show moreAimsPatients with repaired tetralogy of Fallot (rTOF) have an increased risk of ventricular tachycardia (VT), with slow conducting anatomical isthmus (SCAI) 3 as dominant VT substrate. In patients with right bundle branch block (RBBB), SCAI 3 leads to local activation delay with a shift of terminal RV activation towards the lateral RV outflow tract which may be detected by terminal QRS vector changes on sinus rhythm electrocardiogram (ECG).Methods and resultsConsecutive rTOF patients aged ≥16 years with RBBB who underwent electroanatomical mapping at our institution between 2017–2022 and 2010–2016 comprised the derivation and validation cohort, respectively. Forty-six patients were included in the derivation cohort (aged 40±15 years, QRS duration 165±23 ms). Among patients with SCAI 3 (n = 31, 67%), 17 (55%) had an R″ in V1, 18 (58%) had a negative terminal QRS portion (NTP) ≥80 ms in aVF, and 12 (39%) had both ECG characteristics, compared to only 1 (7%), 1 (7%), and 0 patient without SCAI, respectively.Combining R″ in V1 and/or NTP ≥80 ms in aVF into a diagnostic algorithm resulted in a sensitivity of 74% and specificity of 87% in detecting SCAI 3. The inter-observer agreement for the diagnostic algorithm was 0.875. In the validation cohort [n = 33, 18 (55%) with SCAI 3], the diagnostic algorithm had a sensitivity of 83% and specificity of 80% for identifying SCAI 3.ConclusionA sinus rhythm ECG-based algorithm including R″ in V1 and/or NTP ≥80 ms in aVF can identify rTOF patients with a SCAI 3 and may contribute to non-invasive risk stratification for VT. Show less
First the VG-RVPO as a monitoring for PAH in SSc patients was evaluated, here serial measurements of the VG-RVPO, can be used as a follow-up instrument to detect early changes in RV pressure over... Show moreFirst the VG-RVPO as a monitoring for PAH in SSc patients was evaluated, here serial measurements of the VG-RVPO, can be used as a follow-up instrument to detect early changes in RV pressure over time. Then we investigated the role of the VG-RVPO in improving the efficiency of the YEARS algorithm. Neither as a stand-alone diagnostic test nor when combined with the YEARS algorithm, it had any diagnostic value. Then the role of VG-RVPO in estimating the presence of PH, and the prognostic value of an abnormal VG-RVPO in PE patients was evaluated. There was an association between VG-RVPO and RV overload as measured by CTPA. In Chapter 5, the outcome of AAOCA patients is described and linked to pre-and postoperative symptoms. Overall, surgical correction significantly reduces symptoms. The CTOA on pre-and post-operative CTAs of patients with AAOCA was compared and related to anatomy and post-operative outcome. It suggests that CTA can be used to look at the anatomy of AAOCA patients before and after surgery. The last study re-evaluates the late clinical outcome and hemodynamics in patients with TOF. The findings shows, after 17.1 years there was a stabilization of RV function and an impressive durability of the homograft. Show less
Bosch, E. van den; Genuchten, W.J. van; Luijnenburg, S.E.; Duppen, N.; Kamphuis, V.P.; Roos-Hesselink, J.W.; ... ; Helbing, W.A. 2022
Background: To determine the potential prognostic value and clinical correlations of blood biomarkers in a cohort of patients with Tetralogy of Fallot (TOF). Methods: In the setting of multicenter... Show moreBackground: To determine the potential prognostic value and clinical correlations of blood biomarkers in a cohort of patients with Tetralogy of Fallot (TOF). Methods: In the setting of multicenter prospective research studies TOF patients underwent blood sampling, cardiopulmonary exercise testing and low-dose dobutamine stress cardiac magnetic resonance (CMR) imaging. In the blood sample NT-proBNP, GDF-15, Galectin-3, ST-2, DLK-1, FABP4, IGFBP-1, IGFBP-7, MMP-2, and vWF were assessed. During subsequent follow-up, patients were evaluated for reaching the study endpoint (cardiac death, arrhythmia-related hospitalization or cardioversion/ablation, VO2 max <= 65% of predicted). Regression analysis was used to explore the correlation between blood biomarkers (corrected for age and gender) and other clinical parameters. The potential predictive value of blood biomarkers and events were assessed with Kaplan-Meier analysis and Cox proportional hazard analysis. Results: We included 137 Fallot patients, median age 19.2 (interquartile range: 14.6-25.7) years, median age at TOF-repair 0.9 (0.5-1.9) years. After a median follow-up of 8.7 (6.3-10.7) years, 20 (14.6%) patients reached the composite endpoint. In a multivariable cox-regression analysis corrected for age at study baseline, elevated IGFBP-7 and MMP-2 levels were associated with the composite endpoint. We also noted a correlation between DLK-1 and relative change in right ventricular end systolic volume during dobutamine stress CMR (beta = 0.27, p = 0.010), a correlation between FABP4 and Max VO2 (beta = 0.41, p <= 0.001 and between MMP-2 and tricuspid valve E/A ratio (beta = 0.15, p = 0.037). Conclusions: IGFBP-7, MMP-2 and DLK-1 levels are related to cardiac function and long-term outcome in TOF patients. Show less
Background: Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and... Show moreBackground: Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and the effect of pharmaceutical treatment. This study aims to determine factors associated with aortic growth and investigate effects of losartan.Methods and results: We performed a prespedfied analysis from the 1:1 randomized, double-blind REDEFINE trial. Aortic root diameters were measured at baseline and after 2.0 = 0.3 years of follow-up using cardiovascular magnetic resonance (CMR) imaging. A total of 66 patients were included (68% men, age 40 +/- 12 years, baseline aortic root 37 +/- 6 mm, 32% aortic dilatation (>40 mm)). There was a trend towards slow aortic root growth (+0.6 +/- 2.3 mm after two years, p = 0.06) (n = 60). LV stroke volume was the only factor associated with both a larger baseline aortic root (beta: 0.09 mm/ml (95% C.I.:0.02, 0.15), p - 0.010) and with aortic growth during follow-up (beta: 0.04 rim/rill (95% C.L:0.005, 0.066), p = 0.024), after correction for age, sex, and body surface area using linear regression analysis. No treatment effect of losartan was found (p = 0.17).Conclusions: Aortic root dilatation was present in about one-third of rTOF patients. A larger LV stroke volume was associated with both a larger baseline aortic root and ongoing growth. Our findings provide no arguments for lower aortic diameter thresholds for prophylactic surgery compared to the general population. (C) 2020 Elsevier B.V. All rights reserved. Show less
Bosch, E. van den; Cuypers, J.A.A.E.; Luijnenburg, S.E.; Duppen, N.; Boersma, E.; Budde, R.P.J.; ... ; Helbing, W.A. 2020
Aims The aim of this study was to evaluate the possible value of dobutamine stress cardiac magnetic resonance imaging (CMR) to predict adverse outcome in Tetralogy of Fallot (TOF) patients.Methods... Show moreAims The aim of this study was to evaluate the possible value of dobutamine stress cardiac magnetic resonance imaging (CMR) to predict adverse outcome in Tetralogy of Fallot (TOF) patients.Methods and results In previous prospective multicentre studies, TOF patients underwent low-dose dobutamine stress CMR (7.5 mu g/kg/min). Subsequently, during regular-care patient follow-up, patients were assessed for reaching the composite endpoint (cardiac death, arrhythmia-related hospitalization, or cardioversion/ablation, VO2 max <= 65% of predicted). A normal stress response was defined as a decrease in end-systolic volume (ESV) and increase in ejection fraction. The relative parameter change during stress was calculated as relative parameter change= [(parameter(stress) - parameterrest)/parameter(rest)] * 100. The predictive value of dobutamine stress CMR for the composite endpoint was determined using time-to-event analyses (Kaplan-Meier) and Cox proportional hazard analysis. We studied 100 patients [67 (67%) male, median age at baseline CMR 17.8 years (interquartile range 13.5-34.0), age at TOF repair 0.9 years (0.6-2.1)]. After a median follow-up of 8.6 years (6.7-14.1), 10 patients reached the composite endpoint. An abnormal stress response (30% vs. 4.4%, P = 0.021) was more frequently observed in composite endpoint patients. Also in endpoint patients, the relative decrease in right ventricular ESV decreased less during stress compared with the patients without an endpoint (-17 +/- 15 vs. -26 +/- 13 %, P= 0.045). Multivariable analyses identified an abnormal stress response (hazard ratio 10.4; 95% confidence interval 2.5-43.7; P = 0.001) as predictor for the composite endpoint.Conclusion An abnormal ventricular response to dobutamine stress is associated with adverse outcome in patients with repaired TOF. Show less
Nevvazhay, T.; Zeppenfeld, K.; Brouwer, C.; Hazekamp, M. 2020
Ventricular tachyarrhythmia (VT) is a major cause of late morbidity and mortality in patients who underwent surgical repair of tetralogy of Fallot. The majority of VTs are monomorphic macro... Show moreVentricular tachyarrhythmia (VT) is a major cause of late morbidity and mortality in patients who underwent surgical repair of tetralogy of Fallot. The majority of VTs are monomorphic macro-reentrant VT (MVT) and depend on slow conducting areas of diseased myocardium bordered by unexcitable tissue (anatomical isthmuses). Myocardial fibrosis due to surgical incisions, patch material and valve annuli are typical boundaries of anatomical isthmuses (AI). The conducting myocardium between the pulmonary valve and ventricular septum defect patch is called isthmus 3, and the majority of MVTs originate from this area. During pulmonary valve replacement, there is excellent exposure of isthmus 3. Importantly, after pulmonary valve replacement, the homograft may cover important parts of isthmus 3, which makes percutaneous catheter ablation at a later stage impossible. In all patients who need pulmonary valve replacement late after tetralogy of Fallot repair, preoperative electrophysiology study and electroanatomical mapping can identify patients with inducible MVT or slow conduction carrying high risk of MVT. In these patients, intraoperative cryoablation of isthmus 3 should be performed and bidirectional conduction block across the cryoablation line should be demonstrated by intraoperative differential pacing. Show less
Background: An anomalous coronary artery is reported in 2% to 23% of patients with tetralogy of Fallot (TOF). Knowledge of coronary anatomy prior to corrective surgery is vital to avoid damage to... Show moreBackground: An anomalous coronary artery is reported in 2% to 23% of patients with tetralogy of Fallot (TOF). Knowledge of coronary anatomy prior to corrective surgery is vital to avoid damage to vessels crossing the right ventricular outflow tract (RVOT). A meta-analysis on the prevalence of anomalous coronary arteries in TOF is lacking to date. Here, an overview of coronary anomalies in TOF is provided and implications for patient management are discussed.Methods: PubMed, Embase and Web of Science were searched. Analysis was done using Revman 5.3 (Cochrane Community, London). The primary analysis focused on the origin and proximal course of the right and left coronary arteries. In addition, the prevalence of large conus arteries and coronary arteriovenous fistulas (CAVF) was calculated.Results: Twenty-eight studies, encompassing 6956 patients, were included; 6% of TOF patients have an anomalous coronary artery. Hereof, 72% cross the RVOT; the majority of the remaining 28% courses behind the aorta. Six percent of patients have a large conus artery and 4% a CAVF. Other coronary anomalies include a left or right coronary artery from the pulmonary trunk or left or right pulmonary artery, coronary tree hypoplasia and anastomoses between coronary and bronchial arteries.Conclusions: The prevalence of coronary anomalies in TOF is 4-6%. In patients with an anomalous coronary artery, 72% cross the RVOT. The combined risk of encountering an anomalous coronary artery or a large conus artery crossing the RVOT is 10.3%. Coronary anatomy should be defined before surgery and the surgical approach adapted accordingly. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Ventricular tachycardia in repaired Tetralogy of Fallot is associated with significant morbidity and mortality. The dominant substrate of ventricular tachycardia in repaired Tetralogy of Fallot are... Show moreVentricular tachycardia in repaired Tetralogy of Fallot is associated with significant morbidity and mortality. The dominant substrate of ventricular tachycardia in repaired Tetralogy of Fallot are slow conducting anatomical isthmuses in the right ventricular outflow tract. The anatomical isthmuses in repaired Tetralogy of Fallot are the result of the malformation itself or the result of the correction. In this thesis is demonstrated that radiofrequency catheter ablation of anatomical isthmus related ventricular tachycardia can be considered curative and prevent ICD implantation in patients with a preserved cardiac function. Risk stratification for ventricular tachycardia in patients with repaired Tetralogy of Fallot has been difficult. In this thesis is demonstrated that electroanatomical mapping in patients with repaired Tetralogy of Fallot can be used to assess the presence and properties of the anatomical isthmuses in order to perform individualized risk stratification. Further, in this thesis, patients with repaired Tetralogy of Fallot and a right bundle branch block with a QRS duration of ≥150 milliseconds have a blocked or slow conducting anatomical isthmus and should undergo invasive electroanatomical mapping to differentiate between a slow conducting or blocked anatomical isthmus. Show less
