Fallot Patients Research Articles

Cardiac MRI risk factors predict atrial arrhythmia development in repaired tetralogy of Fallot patients

Abstract Background/Introduction Tetralogy of Fallot (TOF) patients with atrial arrhythmias (AA) experience greater morbidity and mortality than do their arrhythmia-free counterparts. Cardiac MRI (cMRI) has proven useful in elucidating risk factors for arrhythmia development in this population, but more work needs to be done to assess the efficacy of predicting AA onset. Purpose To evaluate demographic and clinical metrics, including those routinely assessed on cMRI, that predict AA onset in repaired TOF. Methods 175 repaired TOF patients ≥18 years of age and without prior AA undergoing initial cMRI between 2003 and 2020 were identified from a tertiary U.S. hospital database. Subsequent development of AA (specifically atrial fibrillation, atrial flutter, and atrial tachycardia) was evaluated by chart review and device checks (if present). Kaplan-Meier analysis was used to assess arrhythmia-free survival based on cMRI characteristics, and log-rank test used to compare differences in survival curves. Cutoff values for Kaplan-Meier analysis were the mean value (for the respective variable being measured) of our cohort at the time of their initial cMRI. Results Over a median follow-up of 3.3 years, 30 patients (17%) developed AA, including 16 with atrial fibrillation (53%), 20 with atrial flutter (67%), and 2 with atrial tachycardia (7%). Age at cMRI (p<0.01), history of hypertension (p=0.01), and time from birth to complete TOF repair (p<0.05) predicted AA. cMRI predictors included indexed right ventricular (RV) end diastolic and systolic volumes (both p<0.01), as well as indexed right atrial (RA) volume (p<0.05) and pulmonic regurgitation (PR) fraction (p<0.05). Indexed RV and RA volumes but not left sided chamber volumes predicted the development of atrial fibrillation. All Kaplan-Meier survival distributions were significantly different with the exception of those for right atrial volumes. Conclusions Our study suggests that RA and RV volumes may play a valuable role in predicting atrial arrhythmia onset in the repaired TOF population. Disease progression in a predominantly right-sided heart disease may play a role in predicting the onset of both “right sided” arrhythmias such as atrial flutter, as well as “left sided” arrhythmias such as atrial fibrillation. Additionally, the increased AA burden in patients with mild RV dilation seen in our study may suggest a potential benefit to early pulmonic valve replacement in this patient group. Funding Acknowledgement Type of funding sources: None. Clinical and cMRI CharacteristicsKaplan-Meier Survival Analysis

Risk Factors of Right Ventricular Dysfunction and Adverse Cardiac Events in Patients with Repaired Tetralogy of Fallot.

Aim: This study evaluates the risk factors associated with right ventricular (RV) dilation and dysfunction leading to pulmonary valve replacement (PVR) or adverse cardiac events in repaired Tetralogy of Fallot (rToF) patients. Methods: Data from all rToF patients who underwent magnetic resonance imaging (MRI) evaluation at our hospital between February 2007 and September 2020 were collected. Results: Three hundred and forty-two patients (60% males, 42% older than 18 years), with a median age of 16 years (IQR 13–24) at the time of MRI, were included. All patients underwent complete repair at a median age of 8 months (IQR 5–16), while palliation was performed in 56 patients (16%). One hundred and forty-four patients (42%) subsequently received pulmonary valve replacement (PVR). At the multivariate analysis, male gender was an independent predictor for significant RV dilation, RV and left ventricular (LV) dysfunction. Transventricular ventricular septal defect (VSD) closure and previous palliation significantly affected LV function and RV size, respectively. Male gender and the transventricular VSD closure were independent predictors for PVR. Conclusions: Male gender and surgical history (palliation, VSD closure approach) significantly affected the long-term outcomes in rToF patients and should be taken into consideration in the follow-up management and in PVR timing in this patient population.

Long-term assessment of clinical outcomes and disease progression in patients with corrected Tetralogy of Fallot.

Understanding changes of right ventricular (RV) geometry and function in repaired Tetralogy of Fallot (rToF) patients can improve decision-making for pulmonary valve replacement. Therefore, we aimed to assess the magnitude and clinical correlations of RV changes in rToF patients. Clinical and MRI data of rToF patients who underwent repeated cardiac magnetic resonance imaging (MRI) at two centers between December 2003 and September 2020 were analyzed together with anatomical factors, including RV outflow tract obstruction, pulmonary artery branch stenosis, and tricuspidregurgitation. Adverse cardiac events and/or NYHA class worsening were documented and correlated with MRI changes. QRS length was reported at each MRI. Two-hundred-and-nineteen rToF patients (53% males, aged 20.2 ± 10.1 years) were enrolled. An increase of ventricular dimensions, except LVEDVi, and worsening of right and left ejection fractions were found over an average period of 5 years of follow-up. These changes were statistically significant but within 10% of the initial value. No significant changes were reported on a year-to-year basis, except in a small group of patients (6%) in whom no predictive factors were identified. Despite similar RV dimensions at the first examination, younger patients had a higher RV ejection fraction and a different annual rate of change of ventricular dimensions compared to older ones. Patients with arrhythmias (20%) were more frequently older and had larger RV dimensions but showed no significant correlations with MRI changes/years. Changes in RV dimensions and function occur rarely and very slowly in rToF patients. A small percentage of patients experience a significant worsening in a short time interval without any recognized risk factors. Arrhythmias appear to occur in a small percentage of cases in the late follow-up.

Prevention of infective endocarditis in dental procedures for tetralogy of fallot patients

Objectives: Tetralogy of Fallot (ToF) is a congenital heart defect that is often found in children. Complication that can occur is infective endocarditis caused by bacteria that are often found in the oral cavity. Children with ToF are in a high risk of caries, especially in primary dentition. Preparation of the oral cavity must be done before the cardiac surgery. A proper examination and diagnosis of caries is required in determining the dental treatment to reduce the risk of infective endocarditis.
 Case Report: A boy aged 4 years, weighing 20 kg came to the pediatric dentistry clinic in Surabaya on a referral from Kediri. The patient had ToF with high caries index and will undergo cardiac corrective surgery. Through a brief anamnesis, it was found that this patient's fingernails and lips easily turn blue (cyanosis) if the patient is in an anxious condition. The panoramic photo shows teeth 51, 52, 54, 61, 62, 74, 84 showing radiolucent images from the enamel to the pulp chamber.
 Conclusion: Prophylactic antibiotics should be given to ToF patients before procedures involving the gingiva and pulp. Radiographs are needed to help establish the diagnosis and plan treatment. Proper oral and dental care must be taken to prevent the occurrence of infective endocarditis. Errors in determining the diagnosis can lead to errors in the treatment plan and increase the risk of infective endocarditis.

Seven-year clinical and mechanical follow-up of a Tetralogy of Fallot patient with severe pulmonary regurgitation.

Seven-year clinical and mechanical follow-up of a Tetralogy of Fallot patient with severe pulmonary regurgitation.

Risk factors and long-term outcomes after tetralogy of Fallot repair at an Asian tertiary referral center.

Tetralogy of Fallot is the most common type of cyanotic congenital heart disease. More postoperative tetralogy of Fallot patients grow up than in the past, and these patients need to be followed-up. To investigate the survival and long-term outcomes of patients who underwent total repair of tetralogy of Fallot, and to identify the risk factors for reoperation with pulmonic valve replacement. A total of 403 patients who underwent total tetralogy of Fallot repair at our center during 1997 to 2016 were retrospectively included. Demographic, clinical, treatment, outcome, and follow-up data were collected and analyzed. Median age and body weight at the time of tetralogy of Fallot repair was 4.41 years (range: 0.85-55.28) and 13.58 kg (range: 5.5-68), respectively. The median follow-up was 9.0 years, and overall mortality was 3.2%. The actuarial survival rates at 10 and 20 years were 96.4% and 95.2%, respectively, and the freedom from pulmonic valve replacement was 93.4% and 57.4%, respectively. The median time to indicate pulmonic valve replacement was 13.9 years (range: 6.2-20.5). Multivariate analysis revealed transannular patch technique (hazard ratio: 3.023, 95% confidence interval: 1.34-6.83; p = 0.008) and palliative shunt (hazard ratio: 2.39, 95% confidence interval: 1.16-4.91; p = 0.018) to be independent risk factors for reoperation with pulmonic valve replacement. The rates of overall survival and freedom from pulmonic valve replacement were both high in this study, and both were comparable to the rates reported from other studies. Overall mortality was as low as 3.47%. The need for a transannular patch or palliative shunt should be considered risk factors for a consequent reoperation.

Pulmonary valve replacement may not restore ventricular volume and functional status in patients with pulmonary regurgitation after late tetralogy of Fallot repair

Abstract OBJECTIVES Clinically, tetralogy of Fallot (TOF) patients who underwent repair late (older than 2 years) appears to have worse outcomes after pulmonary valve replacement than patients who underwent repair early. We proceeded to review the clinical features of late-repaired TOF patients who required pulmonary valve replacement. METHODS Fifty patients who underwent pulmonary valve replacement after TOF repair over the age of 2 years from 2000 to 2018 were retrospectively reviewed. Pre- and postoperative cardiac magnetic resonance imaging, cardiopulmonary exercise tests, and cardiac catheterization were analysed. RESULTS The median age of patients at the time of TOF repair and pulmonary valve replacement was 3.6 and 23.4 years, respectively. The median interval from TOF repair to pulmonary valve replacement was 20.5 years. Cardiac magnetic resonance imaging and cardiopulmonary exercise tests were performed at a median of 5.9 and 3.7 years after pulmonary valve replacement, respectively. Cardiac magnetic resonance revealed that there were significant changes in the indexed values of the right ventricle end-diastolic volume (164.7–106.9 ml/m2, P < 0.001), end-systolic volume (101.4–64.9 ml/m2, P < 0.001), stroke volume (66.8–48.0 ml/m2, P = 0.007) and cardiac output (5.1–3.6 l/m2, P = 0.040). Twenty-eight percentage of patients achieved normalization of the right ventricular volume after pulmonary valve replacement. In the exercise test, the maximum rate of oxygen consumption (72.5–69.5%) and oxygen pulse (95.0–83.0%) changed without statistical significance. CONCLUSIONS Although pulmonary valve replacement after late TOF correction improves right ventricular volume status, only a minority of patients achieve normalization of right ventricular end systolic volume and a normal functional status.

Radiofrequency catheter ablation of ventricular tachycardia in patients post surgical repair of tetralogy of Fallot

Objective: To investigate the clinical and electrophysiological features of ventricular tachycardia (VT) in tetralogy of Fallot (TOF) patients post surgical repair (rTOF) and to analyze the therapeutic effect and prognosis of radiofrequency ablation of rTOF-VT. Methods: This is a retrospective study. Consecutive patients with rTOF-VT, who were treated in Fuwai Hospital from January 2015 to March 2020, were enrolled. All the patients underwent right ventricular voltage mapping following routine cardiac electrophysiological examination, followed by linear or homogenizing radiofrequency ablation based on the low-voltage substrate. The clinical features, 3-dimentional electrophysiological substrate mapping, radiofrequency ablation and long-term prognosis of the enrolled patients were analyzed. Acute ablation success was defined as completion of linear or homogenizing ablation or intraoperative evoked VT as destination of the procedure. Patients were followed up at 3 and 6 months post operation and every year thereafter. The endpoints were sudden cardiac death (SCD) and recurrence of ventricular tachycardia. Results: A total of 20 patients with rTOF-VT were enrolled including 14 males with an age of (35.8±11.8) years. The electrocardiogram identified 23 types of ventricular tachycardia, 19 of which were originated from right ventricular inflow tract outlet. The most common clinical manifestations were heart murmur (19 cases, 95%) and syncope (4 cases, 25%). Electroanatomical substrate mapping was performed in 20 patients and evidenced localized or diffuse scar or low-voltage area of right ventricle. Intraoperative electrophysiological tests provoked ventricular tachycardia in 6 patients (30%), including 5 patients with hemodynamics disturbance. The acute success rate of radiofrequency ablation was 95% (19/20). The follow-up time was (31.1±17.7) months and the recurrence rate of ventricular tachycardia was 30% during follow-up period and 5 cases received repeat radiofrequency ablation and there was no recurrent ventricular tachycardia during follow-up post repeat radiofrequency ablation. Conclusions: The voltage substrate mapping under sinus rhythm is a feasible mapping method for rTOF-VT. Linear or flaky radiofrequency ablation of the slow conduction zone is safe and effective treatment strategy, the recurrence rate after the first radiofrequency ablation is still high, and the effectiveness of repeat radiofrequency ablation is satisfactory in this patient cohort.

The impact of native Fallot anatomy on future therapeutic requirements and outcomes at follow-up

BackgroundIn patients with repaired Fallot, subsequent surgical or interventional procedures and adverse cardiac events are frequent. We aimed to evaluate the impact of a simple pre-operative anatomic classification based on the size of the pulmonary valve (PV) annulus and branches on future therapeutic requirements and outcomes.MethodThis is a single-center retrospective analysis of patients operated for Fallot before the age of 2 years, from January 1990. Pre-operative anatomy, surgical and interventional procedures and adverse events were extrapolated from clinical records.ResultsAmong the 312 patients, a description of the PV and pulmonary arteries (PAs) native anatomy was known in 239 patients (male:147, 61.5%), which were divided in the following 3 groups: group 1 (65 patients) with normal size of both PV and PAs; group 2 (108 patients) with PV hypoplasia but normal size PAs; group 3 (66 patients) with concomitant hypoplasia of the PV and PAs. During the 12.7 years (IQR 6.7–17) follow-up time, 23% of patients required at least one surgical or interventional procedure. At Kaplan–Meier analysis, there was a significant difference in requirement of future surgical or interventional procedures among the 3 groups (p < 0,001). At multivariate Cox regression analysis, hypoplasia of PV and PAs was an independent predictor of subsequent procedures (HR:3.1,CI:1.06–9.1, p = 0.03).ConclusionNative anatomy in Tetralogy of Fallot patients affects surgical strategy and follow-up. It would be therefore advisable to tailor patient’s counseling and follow-up according to native anatomy, rather than following a standardized protocol.

Mortality Risk Factors in Tetralogy of Fallot Patients Undergoing Total Correction

A total correction is a preferred treatment for Tetralogy of Fallot patients in every part of the world. However, the mortality in developing countries was as high as 6.9% to 15.3%. This was a retrospective analytic study that analyzed pre and post-operative risk factors that affected mortality on TOF patients that were performed total correction in Indonesia. A total of 47 TOF patients that were performed total correction from January 2016 to September 2019 were enrolled in this study based on the inclusion criteria. Preoperative and post-operative data were obtained from medical records. In this research, the majority of mortality was found in male patients (39.3%), while the female’s rate was lower (36.8%). Overall mortality was 38.3% and one operative death was found. The average age of patients was 84.12 months (12-210 months), whereas the average height (85.56 ± 36.17cm vs. 112.93 ± 21.73) and weight (17.22kg vs. 28.21kg) were lower for mortality patients. Some significant preoperative variables were identified as mortality risk factors such as: age below 60 months (p=0.047), smaller weight and height (p=0.008; p=0.002), abnormal hematocrit (p=0.002), and oxygen saturation below 75% (p=0.018). Significant post-operative risk factors included: temperature above 38.5⁰C (p=0.000), and ventilator time of more than 48 hours (p=0.033). In conclusion, the mortality of TOF patients undergoing a total correction in developing countries was quite high. It was associated with some risk factors, such as younger age, lower weight and height, low oxygen saturation, post-operative fever, and prolonged ventilator time.

Exercise training in patients with corrected tetralogy of Fallot: A protocol for systematic review and meta-analysis.

Background:The arrival of transcatheter mitral valve therapies has provided feasible and safe alternatives to medical and surgical treatments for mitral regurgitation. The aim of this study is to estimate the relative efficacy and safety of exercise training in patients with corrected tetralogy of Fallot through meta-analysis.Methods: A systematic search will be performed using PubMed, EMBASE, the Cochrane Library, Web of Science, CBM, CNKI, WanFang Data, and VIP to include random controlled trials or nonrandom controlled trials comparing the efficacy and safety of exercise training in corrected tetralogy of Fallot patients. The risk of bias for the included nonrandom controlled studies will be evaluated according to Risk of Bias in Nonrandomized Studies of Interventions. We will use the Cochrane Collaboration's tool (version 2 of the Cochrane risk of bias tool for randomized trials) to assess risk of bias of included random controlled trials. Revman 5.4 and STATA 15.0 will be used to complete the meta-analysis and generate forest plots. Grading of recommendations assessment, development, and evaluation will be used to assess the quality of evidence.Results: The results of this systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion: This study will provide broad evidence of efficacy and safety of exercise training in patients with corrected tetralogy of Fallot and provide suggestions for clinical practice and future research.Protocol registration number:INPLASY202150006.

Dexmedetomidine Protects Human Cardiomyocytes Against Ischemia-Reperfusion Injury Through α2-Adrenergic Receptor/AMPK-Dependent Autophagy.

Background: Ischemia-reperfusion injury (I/R) strongly affects the prognosis of children with complicated congenital heart diseases (CHDs) who undergo long-term cardiac surgical processes. Recently, the α2-adrenergic receptor agonist Dexmedetomidine (Dex) has been reported to protect cardiomyocytes (CMs) from I/R in cellular models and adult rodent models. However, whether and how Dex may protect human CMs in young children remains largely unknown. Methods and Results: Human ventricular tissue from tetralogy of Fallot (TOF) patients and CMs derived from human-induced pluripotent stem cells (iPSC-CMs) were used to assess whether and how Dex protects human CMs from I/R. The results showed that when pretreated with Dex, the apoptosis marker-TUNEL and cleaved caspase 3 in the ventricular tissue were significantly reduced. In addition, the autophagy marker LC3II was significantly increased compared with that of the control group. When exposed to the hypoxia/reoxygenation process, iPSC-CMs pretreated with Dex also showed reduced TUNEL and cleaved caspase 3 and increased LC3II. When the autophagy inhibitor (3-methyladenine, 3-MA) was applied to the iPSC-CMs, the protective effect of Dex on the CMs was largely blocked. In addition, when the fusion of autophagosomes with lysosomes was blocked by Bafilomycin A1, the degradation of p62 induced by Dex during the autophagy process was suspended. Moreover, when pretreated with Dex, both the human ventricle and the iPSC-CMs expressed more AMP-activated protein kinase (AMPK) and phospho AMPK (pAMPK) during the I/R process. After AMPK knockout or the use of an α2-adrenergic receptor antagonist-yohimbine, the protection of Dex and its enhancement of autophagy were inhibited. Conclusion: Dex protects young human CMs from I/R injury, and α2-adrenergic receptor/AMPK-dependent autophagy plays an important role during this process. Dex may have a therapeutic effect for children with CHD who undergo long-term cardiac surgical processes.

Exercise capacity in patients with repaired Tetralogy of Fallot aged 6 to 63 years

ObjectivesThis study aimed to provide a perspective for the interpretation of exercise capacity (peakVO2) in patients with repaired Tetralogy of Fallot (patients with rTOF) by describing the course of peakVO2...

Right ventricular diastolic function in post-surgical Tetralogy of Fallot patients: A pilot study to make a comparison between echocardiography and cardiac MRI

Background: right ventricular (RV) systolic dysfunction is associated with poor outcomes in Tetralogy of Fallot (ToF) patients. Conversely, the influence of diastolic dysfunction in this setting is poorly known. In addition, evaluation of RV diastolic function by cardiac MRI is rarely performed.Materials and methods: twenty-four surgically treated ToF patients were enrolled in the study (54% males; median age at study: 28 (18–50) years; median age at surgery: 1.9 (0.4–8.2) years. They were studied by echocardiography to assess RV diastolic function in terms of traditional and TDI-derived parameters. At cardiac MRI, RV diastolic function was assessed by using phase-contrast analysis of flow through the tricuspid valve in short axis view. Diastolic dysfunction was graded as impaired relaxation, pseudo-normal, or restrictive physiology.Results: fifteen (62.5%) ToF subjects had echocardiographic evidence of diastolic dysfunction and eleven (45.8%) at cardiac MRI. Statistically significant correlation between echocardiographic and cardiac MRI parameters of diastolic dysfunction was weak (p < 0.05). The degree of RV diastolic dysfunction (expressed as E/E’ at TDI) was associated with right atrial volume indexed for body surface area at cardiac MRI (p < 0.0001). Greater number of interim palliative procedures was associated with higher E/E' (RV diastolic dysfunction) at echocardiography (p < 0.0003).Conclusions: diastolic dysfunction, as determined by echocardiography and cardiac MRI-derived measures, is prevalent in ToF. These measures are weakly associated with each other. Notwithstanding the limitations of this pilot study, the development of cardiac MRI parameters capable of correlating with RV relaxation is needed in ToF setting.

The role of exercise testing in congenital heart disease patients after coronary artery reimplantation

IntroductionThe Ross procedure requires like the arterial switch operation (ASO) coronary artery reimplantation. There is no information on coronary artery stenosis at the site of the reimplantation in Ross patients as has been described for ASO patients. This study assessed therefore the prevalence of positive exercise tests (pETs) suggesting myocardial ischemia in Ross and ASO patients in comparison to tetralogy of Fallot patients (TOF), the latter not undergoing coronary artery reimplantation. The study evaluated further, whether a coronary artery complication was confirmed by a supplementary non- and/or invasive evaluation. MethodsResults of exercise tests, echocardiography, coronary computed tomography (CCT) and coronary angiography (CA) were retrospectively reviewed in 30 Ross, 14 ASO and 30 TOF patients. ResultsExercise capacity did not differ between groups. There was a trend to more frequent pETs in Ross patients (Ross vs. ASO vs. TOF, N, %): 8 (27) vs. 1 (7) vs. 2 (7) p = 0.062. CCT was performed in 30% Ross, 21% ASO, 3% TOF (p = 0.023); CA in 20% Ross, 21% ASO and 13% TOF patients (p = 0.727). None of these investigations revealed a coronary artery stenosis. Patients with pET showed a higher right ventricular outflow tract (RVOT) gradient (44 ± 30 vs. 22 ± 13 mmHg, p = 0.004) and more frequently a severe RVOT stenosis (27 vs. 0%, p < 0.006). ConclusionspETs are rather related to RVOT stenosis than to coronary artery complications after Ross procedure, ASO and TOF repair. The role of exercise testing for detection of myocardial ischemia is limited and should be restricted to evaluation of exercise capacity.

The Effect of Geometric and Hemodynamic Parameters on Blood Flow Efficiency in Repaired Tetralogy of Fallot Patients.

Surgical repair of Tetralogy of Fallot (TOF) involves a series of steps to remove right ventricular outflow tract and pulmonary artery obstruction. However, the large degree of anatomic variability among preoperative TOF patients may impact the effectiveness of different repair strategies and, subsequently, different geometric modifications for different patients. This study investigates the relationships between geometric and hemodynamic parameters and mechanical energy efficiency for a patient-specific dataset of 16 postoperative TOF repairs, using morphometric and statistical shape analyses, as well as computational fluid dynamics simulations with physiologically-relevant inlet and outlet boundary conditions. Quantitatively, negative correlations were found between the right and left pulmonary artery centerline tract cumulative torsion and energy efficiency (r = -0.65, p = 0.01, for both). A positive correlation was also found for a statistical shape mode associated with skewing of the geometric sub-regions (r = 0.61, p = 0.01). Qualitatively, medium- and low-efficiency geometries exhibit disturbed flow and much more proximal vortex formation as compared to a high-efficiency geometry. Thus, it is recommended, as much as possible, to both relieve and avoid the introduction of torsion into the patient's anatomy during surgical repair of TOF.

Screening of NKX2.5 gene in Moroccan Tetralogy of Fallot (TOF) patients: worldwide mutation rate comparisons show a significant association between R25C variant and TOF phenotype

BackgroundTetralogy of Fallot is the most prevalent cyanotic congenital heart disease, occurring in 1/3 600 live births. This disorder comprises ventricular septal defect, right ventricular outflow obstruction, over-riding aorta, and right ventricular hypertrophy. The present study aims to reveal the spectrum of Nk2 homeobox 5 (NKX2-5) variants identified in a Moroccan non-syndromic tetralogy of Fallot cohort and to compare mutation rate with different studies from all over the world. Thirty-one patients with non-syndromic tetralogy of Fallot were recruited in this cross-sectional study. DNAs were extracted, and coding regions of NKX2.5 were PCR-amplified and sequenced. The obtained sequences were analyzed using different bioinformatics tools. Statistical comparisons were carried out using the R software.ResultsR25C mutation was found in two patients, in association with the E21E variant. The latter variant was frequently observed in the population and seems to have a potential altering effect on the splicing process. The NKX2.5 mutation rate in our tetralogy of Fallot population is around 6.4%, and no significant difference was noticed in comparison with previous studies. At the same time, a comparison of R25C mutation rate between atrial septal defect and tetralogy of Fallot worldwide populations shows a particular association of R25C mutation with tetralogy of Fallot phenotype.ConclusionsThis study reveals a consistency between our NKX2.5 mutation rate and those of different tetralogy of Fallot populations around the world. Our findings suggest a possible combined effect of R25C mutation and E21E variant on the carriers and emphasize particularly the significant association of R25C mutation with tetralogy of Fallot, which highlights the importance of an anticipative screening for TOF phenotype among the carriers’ offspring at the perinatal period.

Moving beyond size: vorticity and energy loss are correlated with right ventricular dysfunction and exercise intolerance in repaired Tetralogy of Fallot

BackgroundThe global effect of chronic pulmonary regurgitation (PR) on right ventricular (RV) dilation and dysfunction in repaired Tetralogy of Fallot (rTOF) patients is well studied by cardiovascular magnetic resonance (CMR). However, the links between PR in the RV outflow tract (RVOT), RV dysfunction and exercise intolerance are not clarified by conventional measurements. Not all patients with RV dilation share the same intracardiac flow characteristics, now measurable by time resolved three-dimensional phase contrast imaging (4D flow). In our study, we quantified regional vorticity and energy loss in rTOF patients and correlated these parameters with RV dysfunction and exercise capacity.MethodsrTOF patients with 4D flow datasets were retrospectively analyzed, including those with transannular/infundibular repair and conduit repair. Normal controls and RV dilation patients with atrial-level shunts (Qp:Qs > 1.2:1) were included for comparison. 4D flow was post-processed using IT Flow (Cardioflow, Japan). Systolic/diastolic vorticity (ω, 1/s) and viscous energy loss (VEL, mW) in the RVOT and RV inflow were measured. To characterize the relative influence of diastolic vorticity in the two regions, an RV Diastolic Vorticity Quotient (ωRVOT-Diastole/ωRV Inflow-Diastole, RV-DVQ) was calculated. Additionally, RVOT Vorticity Quotient (ωRVOT-Diastole/ωRVOT-Systole, RVOT-VQ) and RVOT Energy Quotient (VELRVOT-Diastole/VELRVOT-Systole, RVOT-EQ) was calculated. In rTOF, measurements were correlated against conventional CMR and exercise stress test results.Results58 rTOF patients, 28 RV dilation patients and 12 controls were included. RV-DVQ, RVOT-VQ, and RVOT-EQ were highest in rTOF patients with severe PR compared to rTOF patients with non-severe PR, RV dilation and controls (p < 0.001). RV-DVQ positively correlated with RV end-diastolic volume (0.683, p < 0.001), PR fraction (0.774, p < 0.001) and negatively with RV ejection fraction (− 0.521, p = 0.003). Both RVOT-VQ, RVOT-EQ negatively correlated with VO2-max (− 0.587, p = 0.008 and − 0.617, p = 0.005) and % predicted VO2-max (− 0.678, p = 0.016 and − 0.690, p = 0.001).ConclusionsIn rTOF patients, vorticity and energy loss dominate the RVOT compared to tricuspid inflow, correlating with RV dysfunction and exercise intolerance. These 4D flow-based measurements may be sensitive biomarkers to guide surgical management of rTOF patients.

Coronary artery anomalies in tetralogy of Fallot patients evaluated by multi slice computed tomography; myocardial bridge is not a rare finding.

Based on coronary angiography and interoperative inspection, anomalous origin of coronary artery crossing the right ventricular outflow tract (RVOT) is common in tetralogy of Fallot (TOF) patients. However, other coronary anomalies may be underestimated due to the overlying myocardium, epicardial fat, or adhesions due to previous palliative surgery. Currently, coronary artery visibility dramatically improved by multislice computed tomography (MSCT). We performed this study to assess the coronary arteries anatomy in TOF patients using MSCT.All TOF patients underwent MSCT examination at our centre from 2013 till 2019 were included. Assessment of the coronary arteries’ origin and course were performed. Presence of myocardial bridge were assessed, and indexed RV mass was calculated.318 TOF patients were included, median age 2 years (range 1 month–46 years), 175 males (55%). The abnormal coronary artery origin and course were detected in 20 patients (6%); coronary artery crossed RVOT in 13 patients (65%), 5 patients (25%) had a retro-aortic course and 2 patient (10%) had inter-arterial course. Myocardial bridges of left anterior descending artery or/and right coronary artery were reported in 100 patients (36%), no myocardial bridge of left circumflex was reported. RV mass was 29.0 ± 21.1 g/m2. There was no correlation between RV mass and presence of myocardial bridges.MSCT is a useful imaging modality for detection of coronary arteries anomalies in TOF patients. Coronary artery crossing RVOT is not the only abnormal course and myocardial bridging is not a rare finding. Further studies are needed to demonstrate the clinical significance of these observations.

Serial MRI-based right ventricular mechanical wall stress measurements and their association with right ventricle function in patients with repaired Tetralogy of Fallot

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Stichting Hartekind en Thorax Foundation Background Optimal timing of pulmonary valve replacement (PVR) in Tetralogy of Fallot (TOF) patients remains challenging. Wall stress is considered to be a possible early marker of right ventricular (RV) dysfunction. With patient-specific computational models, wall stress can be determined regionally and with high accuracy, especially in complex shaped ventricles such as in TOF patients. We aimed to 1) develop patient-specific computational models to assess RV diastolic wall stresses and 2) investigate the association of wall stresses and their change over time with functional parameters in TOF patients. Methods Repaired TOF patients with at least moderate pulmonary regurgitation (PR) and prior to PVR were included. MRI-based patient-specific computational ventricular models were created (figure). The ventricular geometry was created by stacking endo- and epicardial contours traced on short axis SSFP cine images. Pressure in the right ventricle was estimated from echocardiography. Mid-diastolic wall stress in the RV free wall was analysed globally and regionally (basal, mid, apical, anterior, lateral and posterior) at two time points. RV ejection fraction (RVEF), NT-proBNP and exercise tests (% maximum predicted workload) were used as outcomes for RV function. Associations between wall stresses and outcomes were investigated using linear mixed models adjusted for follow-up duration. Results Five males and five females were included with an age at baseline of 24 (IQR 16-28) years and RV end-diastolic volume of 140 (IQR 127-144) ml/m2. The period between the two time points was 7.0 (IQR 5.8-7.3) years. Global wall stress of the RV free wall combining both time points was 5.8 kPa (IQR 5.2-7.2). There was no statistical difference between baseline and follow-up global wall stress. The mean wall stresses in the mid region was 1.69 kPa (p &amp;lt; 0.01) higher than in the basal region and was 1.05 kPa (p = 0.03) higher than in the apical region cross-sectionally. The wall stress also increased more in the mid region compared to basal and apical region, corrected for duration of follow-up. Patients with more severe PR at baseline demonstrated a higher increase of global wall stress over time (p = 0.02), especially in lateral free wall. Higher global free wall stresses were cross-sectionally independently associated with lower RVEF, adjusted for LVEF and RVEDV (β=-1.29 % RVEF per kPa increase in wall stress, p = 0.01). This association was most prominent in the anterior, basal and mid part. No statistically significant association was found between wall stress, NT-proBNP, and exercise capacity. Conclusions This study generated a novel MRI-based method to calculate wall stress in geometrically complex ventricles. Wall stress associated negatively with RVEF in patients with TOF and PR. This promising tool for RV wall stress analysis can be used in future larger studies to validate these preliminary findings and to assess the predictive value of wall stress in TOF. Abstract Figure.