RT In Patients Research Articles

Phenotypic clustering of repaired Tetralogy of Fallot using unsupervised machine learning

ObjectiveRepaired Tetralogy of Fallot (rTOF), a complex congenital heart disease, exhibits substantial clinical heterogeneity. Accurate prediction of disease progression and tailored patient management remain elusive. We aimed to categorize rTOF patients into distinct phenotypes based on clinical variables and variables obtained from cardiac magnetic resonance (CMR) imaging. MethodsA retrospective observational cohort study of rTOF patients with at least two CMR assessments between 2005 and 2022 was performed. From patient records, clinical variables, CMR measurements, and electrocardiogram data were collected and processed. Baseline and follow-up variables between subsequent CMR studies were used to assess both inter- and intrapatient disease heterogeneity. Subsequently, unsupervised machine learning was performed, involving dimensionality reduction using principal component analysis and K-means clustering to identify different phenotypic clusters. ResultsIn total, 155 patients (54.2 % male, median 14.9 years) were included and followed for a median duration of 9.9 years. A total of 459 CMR studies were included in analysis for the identification of phenotypic clusters. Following analysis, we identified four distinct rTOF phenotypes: (1) stable/slow deteriorating, (2) deteriorating, structural remodeling, (3) deteriorated indicated for pulmonary valve replacement, and lastly (4) younger patients with coexisting anomalies. These phenotypes exhibited differential clinical profiles (p < 0.01), cardiac remodeling patterns (p < 0.01), and intervention rates (p < 0.01). ConclusionsUnsupervised machine learning analysis unveiled four discrete phenotypes within the rTOF population, elucidating the substantial disease heterogeneity on both a population- and patient-level. Our study underscores the potential of unsupervised machine learning as a valuable tool for characterizing complex congenital heart disease and potentially tailoring interventions.

Long-term outcomes of ventricular tachycardia ablation in repaired tetralogy of Fallot: Systematic review and meta-analysis.

Ventricular tachycardia (VT) remains a risk in repaired Tetralogy of Fallot (rTOF); however, long-term benefits of VT ablation have not been established. This study compares the outcomes of rTOF patients with and without VT ablation. We searched multiple databases examining the outcomes of rTOF patients who had undergone VT ablation compared to those without ablation. Primary outcomes were VT recurrence, sudden cardiac death (SCD), and all-cause mortality. Subgroup analysis was conducted based on the type of ablation (catheter and surgical). Slow-conducting anatomical isthmus (SCAI)-based catheter ablation (CA) was also analyzed separately. The secondary outcome was the risk factors for the pre-ablation history of VT. Fifteen cohort studies with 1459 patients were included, 21.4% exhibited VTs. SCAI was found in 30.4% of the population, with 3.7% of non-inducible VT. Factors significantly associated with VT before ablation included a history of ventriculostomy, QRS duration ≥180 ms, fragmented QRS, moderate to severe pulmonary regurgitation, high premature ventricular contractions burden, late gadolinium enhancement, and SCAI. Ablation was only beneficial in reducing VTs recurrence in SCAI-based CA (risk ratio (RR) 0.11; 95% CI 0.03 to 0.33. p < 0.001; I2 = 0%) with no recurrence in patients with preventive ablation (mean follow-up time 91.14 ± 77.81 months). The outcomes of VT ablation indicated a favorable trend concerning SCD and all-cause mortality (RR 0.49 and 0.44, respectively); however, they were statistically insignificant. SCAI-based CA has significant advantages in reducing VT recurrence in rTOF patients. Risk stratification plays a key role in determining the decision to perform ablation.

Systematic right ventricular electrophysiologic evaluation in patients with repaired tetralogy of Fallot before pulmonary valve replacement

Abstract Introduction Adults with repaired tetralogy of Fallot (rToF) are prone to develop ventricular tachycardia (VT) in adulthood, due to reentry related to slowly conducting anatomical isthmuses (SCAI). Pulmonary valve replacement (PVR) in patients without history of VT, may lead to obliteration of unrecognized SCAI with subsequent catheter ablation failure; electrophysiologic study is thus recommended before PVR. A systematic evaluation of the topology of SCAI in this population is, however, scant. Methods Consecutive rToF patients undergoing PVR with native right ventricular outflow tract were studied with pre-PVR EPS. Electroanatomical mapping with systematic evaluation of all possible anatomical isthmuses (AI) with pacemapping, activation mapping in sinus/paced rhythm and bipolar voltage mapping was performed (AI1: anterior scar/patch to tricuspid annulus; AI2: anterior scar to pulmonary annulus; AI3: pulmonary annulus to ventricular septal defect – VSD- patch; AI4: VSD to tricuspid annulus). Conduction velocity (CV) across all documented AI was calculated (ratio between the distance among the nearest point with bipolar voltage &amp;gt;1.5 mV and their difference in activation timing). Ventricular programmed stimulation was performed at 2 sites (apex and outflow tract) with drive train ad 600/400 ms, up to three extrastimuli until refractoriness or induction, during baseline and isoproterenol infusion. Radiofrequency catheter ablation (RFCA) was performed in all patients with inducible VT and/or SCAI, aiming at conduction block across the SCAI validated with differential pacing. Results Between May 2023 and November 2023, 10 patients with rToF and 1 double outlet right ventricle were studied (73% males, age 46±10 years; 54% with a previous shunt, 46% with a previous transannular patch, 27% pulmonary valvotomy and infundibular boring; median age at surgery 4 years, interquartile range 3-6). EPS was positive for inducible VT in 4 patients (mean cycle length 297 ms, 3 with left bundle branch morphology and 1 right bundle branch morphology, all inferior axis) and polymorphic VT in 1. AI1 was present in 5 patients, AI2 in 5, AI3 in 7, AI 4 in 2. At least 1 SCAI was present in 7 patients (64%), 2 SCAI in 3 patients (43% of patients with SCAI; in every patient SCAI3+SCAI2 in 2 and SCAI 4 in 1 patient). There were no SCAI1; there were 3 SCAI 2 (mean CV 0.43 m/s), 4 SCAI 3 (mean CV 0.3 m/s), 1 SCAI 4 (CV 0.4 m/s). RFCA was performed in 8 patients; acute success was achieved in all patients, achieving bidirectional conduction block across treated SCAI and non-inducibility of VT. Conclusions SCAI are often present in rToF candidate to PVR and without clinical history of spontaneous VT, involving prevalently SCAI3 and SCAI2. Inducible VT is not sufficient as a marker of arrhythmic risk and SCAI should be better sought for. RFCA of SCAI with bidirectional conduction block is acutely highly efficacious.

Tetralogy of Fallot regurgitation energetics and kinetics: an intracardiac flow analysis of the right ventricle using computational fluid dynamics.

Repaired Tetralogy of Fallot (rTOF) patients suffer from pulmonary regurgitation and may require pulmonary valve replacement (PVR). Cardiac magnetic resonance imaging (cMRI) guides therapy, but conventional measurements do not quantify the intracardiac flow effects from pulmonary regurgitation or PVR. This study investigates intracardiac flow parameters of the right ventricle (RV) of rTOF by computational fluid dynamics (CFD). cMRI of rTOF patients and controls were retrospectively included. Feature-tracking captured RV endocardial contours from long-axis/short-axis cine. Ventricular motion was reconstructed via diffeomorphic mapping, serving as domain boundary for CFD simulations. Vorticity (1/s), viscous energy loss (ELoss, mJ/L) and turbulent kinetic energy (TKE, mJ/L) were quantified in RV outflow tract (RVOT) and RV inflow. These parameters were normalized against total RV kinetic energy (KE) and RV inflow vorticity to derive dimensionless metrics. Vorticity contours by Q-criterion were qualitatively compared. rTOF patients (n = 15) had mean regurgitant fraction 38 ± 12% and RV size 162 ± 35mL/m2. Compared to controls (n = 12), rTOF had increased RVOT vorticity (142.6 ± 75.6/s vs. 40.4 ± 11.8/s, p < 0.0001), Eloss (55.6 ± 42.5 vs. 5.2 ± 4.4mJ/L, p = 0.0004), and TKE (5.7 ± 5.9 vs. 0.84 ± 0.46mJ/L, p = 0.0003). After PVR, there was decrease in normalized RVOT Eloss/TKE (p = 0.0009, p = 0.029) and increase in normalized tricuspid inflow vorticity/KE (p = 0.0136, p = 0.043), corresponding to reorganization of the "donut"-shaped tricuspid ring-vortex. The intracardiac flow in rTOF patients can be simulated to determine the impact of PVR and improve the clinical indications guided by cardiac imaging.

Computational Analysis of Blood Flow in Healthy Pulmonary Arteries in Comparison to Repaired Tetralogy of Fallot Results: A Small Cohort Study

Characterization of the physiological hemodynamic environment in normal pulmonary arteries is a key factor in understanding pathological conditions. This study aimed to analyze the morphology and hemodynamics in the healthy adult pulmonary bifurcation in comparison to age-matched repaired Tetralogy of Fallot (rTOF) geometries. The pulmonary trunk of five healthy volunteers was reconstructed from 4D Flow-MRI data and was compared to rTOF results. Subject-specific boundary conditions were assigned in both the inlet and outlets of the models, and flow characteristics were analyzed computationally. The morphological and flow features were consistent among the healthy geometries, highlighting the ability of an averaged geometry derived from this small cohort to capture the main flow characteristics. A slightly higher mean time-averaged wall shear stress (TAWSS) was found in the right pulmonary artery, which was also the branch with a higher mean curvature and local Reynolds number. Compared to rTOF results, the averaged healthy geometry demonstrated more than an 8-fold lower value in TAWSS, with the individual patient-specific healthy volunteers showing further reduced TAWSS than the rTOF patients. These observations could be useful in clinical assessment and decision making based on hemodynamic indices.

Correlation of ECG and cardiac MRI for assessment of ventricular hypertrophy and dilatation in adults with repaired tetralogy of Fallot

BackgroundSurgically repaired Tetralogy of Fallot (rTOF) is associated with progressive right ventricular hypertrophy (RVH) and dilation (RVD). Accurate estimation of RVH/RVD is vital for the ongoing management of this patient population. The utility of the ECG in evaluating patients with rTOF with pre-existing right bundle branch block (RBBB) has not been studied. We aimed to determine the sensitivity/specificity of currently established ECG criteria in detecting RVH/RVD in this patient population. MethodsWe included consecutive patients diagnosed with rTOF who underwent CMR performed at our regional referral centre between January 2012 and December 2019. Each CMR was assessed for LVH, LVD, RVH and or RVD. The ECG corresponding to the CMR was then used to determine RVH/LVH for specificity and sensitivity analysis. ResultsOur study included 163 consecutive rTOF patients. The specificity for ECG-based criteria for LVH was 100.00% (95% C.I. (87.75, 100.00)), and the sensitivity was 7.19% (95% C.I. (3.15, 12.83)). When RBBB was present, specificity for RVH was 100.00% (95% C.I. (84.56, 100.00)), and sensitivity was 7.69% (95% C.I. (3.75, 13.69)). When RBBB was absent, specificity for RVH was 100.00% (95% C.I. (15.81, 100.00)), and sensitivity was 0.00% (95% C.I. (0.00, 33.63)). A regression model with the entire group of 163 ToF patients, based on the Sokolow-Lyon criterion (sum of R in V1 + S in V5/V6), produced a new suggested criterion for the diagnosis of RVH in patients with rTOF, which was a sum of R in V1 + S in V5/V6 greater than 13.25 mm. This model's sensitivity for RVH detection was 69.1%, and specificity was 36.8%. ConclusionsStandard ECG voltage criteria have poor sensitivity for detecting right and left ventricular chamber hypertrophy and dilatation in patients with rTOF, so current ECG criteria should not be used to monitor RVH/RVD in this patient population.

Cardiopulmonary Exercise Testing after Surgical Repair of Tetralogy of Fallot-Does Modality Matter?

Despite a successful repair of tetralogy of Fallot (rToF) in childhood, residual lesions are common and can contribute to impaired exercise capacity. Although both cycle ergometer and treadmill protocols are often used interchangeably these approaches have not been directly compared. In this study we examined cardiopulmonary exercise test (CPET) measurements in rToF. Inclusion criteria were clinically stable rToF patients able to perform a cardiac magnetic resonance imaging (CMR) and two CPET studies, one on the treadmill (incremental Bruce protocol) and one on the cycle ergometer (ramped protocol), within 12 months. Demographic, surgical and clinical data; functional class; QRS duration; CMR measures; CPET data and international physical activity questionnaire (IPAQ) scores of patients were collected. Fifty-seven patients were enrolled (53% male, 20.5 ± 7.8 years at CPET). CMR measurements included a right ventricle (RV) end-diastolic volume index of 119 ± 22 mL/m2, a RV ejection fraction (EF) of 55 ± 6% and a left ventricular (LV) EF of 56 ± 5%. Peak oxygen consumption (VO2)/Kg (25.5 ± 5.5 vs. 31.7 ± 6.9; p < 0.0001), VO2 at anaerobic threshold (AT) (15.3 ± 3.9 vs. 22.0 ± 4.5; p < 0.0001), peak O2 pulse (10.6 ± 3.0 vs. 12.1± 3.4; p = 0.0061) and oxygen uptake efficiency slope (OUES) (1932.2 ± 623.6 vs. 2292.0 ± 639.4; p < 0.001) were significantly lower on the cycle ergometer compared with the treadmill, differently from ventilatory efficiency (VE/VCO2) max which was significantly higher on the cycle ergometer (32.2 ± 4.5 vs. 30.4 ± 5.4; p < 0.001). Only the VE/VCO2 slope at the respiratory compensation point (RCP) was similar between the two methodologies (p = 0.150). The majority of CPET measurements differed according to the modality of testing, with the exception being the VE/VCO2 slope at RCP. Our data suggest that CPET parameters should be interpreted according to test type; however, these findings should be validated in larger populations and in a variety of institutions.

Morphometrics predicts the differential regurgitant fraction in bilateral pulmonary arteries of patients with repaired tetralogy of fallot.

In patients with repaired tetralogy of Fallot (rTOF), the regurgitant fraction (RF) in left pulmonary artery (LPA) and right pulmonary artery (RPA) is usually unequal. The morphometrics may play a crucial role in this RF discrepancy. Cardiovascular MR of 79 rTOF patients and 20 healthy controls were retrospectively enrolled. Forty-four from the 79 patients were matched in age, sex and body surface areato the 20 controls andwere investigated for: (1) phase-contrast flow of main pulmonary artery (MPA), LPA, and RPA; (2) vascular angles: the angles between the thoracic anterior-posterior line (TAPL) with MPA (θM-AP), MPA with RPA (θM-R), and MPA with LPA (θM-L); (3) cardiac angle, the angle between TAPL and the interventricular septum; (4) area ratio of bilateral lung and hemithorax regions. Compared with the 20 controls, the 44 rTOF patients exhibited wider θM-AP, sharper θM-L angle, and a smaller θM-L/θM-R ratio. In the 79 rTOF patients, LPA showed lower forward, backward, and net flow, and greater RF as compared with RPA. Multivariate analysis showed that the RF of LPA was negatively associated with the θM-L/θM-R ratio and the age at surgery (R2 = 0.255). Conversely, the RF of RPA was negatively associated with the left lung/left hemithorax area ratio and cross-sectional area (CSA) of LPA, and positively associated with CSA of RPA and MPA (R2 = 0.366). In rTOF patients, the RF of LPA is more severe than that of RPA, which may be related to the vascular morphometrics. Different morphometric parameters areindependently associated with the RF of LPA or RPA, which may offer potential insights for surgical strategies.

Impact of pulmonary stenosis on right ventricular global longitudinal strain in repaired tetralogy of Fallot patients post transcatheter pulmonary valve replacement.

Mixed pulmonary disease with pulmonary regurgitation (PR) and stenosis (PS) in repaired tetralogy of Fallot (rTOF) can negatively impact ventricular health. Myocardial strain has been shown to be more sensitive at detecting occult ventricular dysfunction compared to right ventricular ejection fraction (RV EF). We hypothesize that rTOF patients with predominant PS will have lower RV global longitudinal strain (RV GLS) prior to and post-transcatheter pulmonary valve replacement (TPVR). A retrospective cohort of rTOF patients who underwent cardiac magnetic resonance (CMR) and cardiac catheterization for right ventricular pressure (RVSP) measurement were analyzed at three time points: before valve implantation, at discharge and within 18 months post-TPVR. Patients were dichotomized into three groups based on RVSP: 0%-49%, 50%-74%, and >75%. RV GLS and left ventricular (LV) GLS by speckle tracking echocardiography (STE) were obtained from the apical 4-chamber using TomTec software (TOMTEC IS, Germany). Forty-eight patients were included. Every 14.3% increase in preimplantation RVSP above 28% was associated with an absolute magnitude 1% lower RV GLS (p=.001). Preimplantation RVSP when 75% or higher had 3.36% worse RV GLS than the lowest bin (p=.014). Overall, average RV strain magnitude was higher when preimplantation RVSP was less than 50% and had greater improvement over the three time points. Higher post implantation RVSP correlated with lower strain magnitude. Patients with significant PS (>50%) may benefit from earlier PVR and not depend solely on RV size and EF. Myocardial strain may be a more sensitive marker of function; however, larger, prospective studies are needed.

Biventricular interaction and aortic function in adult patients with repaired tetralogy of Fallot: a two-dimensional-three-dimensional speckle-tracking echocardiographic study.

In patients late after correction of tetralogy of Fallot (TOF), the combined effects of pre-operative hypertrophy and hypoxia, ventricular interdependence, acquired post-operative lesions such as pulmonary or aortic regurgitation, and congenital vasculopathy may result in impaired right ventricular (RV) and left ventricular (LV) function. The aim of the present study was to investigate the interventricular interactions in repaired TOF (rTOF) and the impact of aortic function on biventricular performance using two-dimensional (2D-STE) and three-dimensional speckle-tracking echocardiography (3D-STE). Twenty-five adult patients with rTOF and 25 age- and gender-matched healthy controls were studied. LV and RV volumes were determined by 3D-STE and cardiac magnetic resonance. LV and RV longitudinal strains (LVLS and RVLS) and LV and RV area strains (LVAS and RVAS) and LV twist/rotation were calculated by 3D-STE. Ascending aorta circumferential strain (AAo-CS) was obtained using 2D-STE. LV 3D-STE parameters were decreased in rTOF patients compared with controls even in patients with normal ejection fraction. AAo-CS was decreased (6.7 ± 1.9 vs. 10.1 ± 2.6, P = 0.003) in rTOF patients compared with controls even in the presence of normal aortic dimensions and correlated with AAo diameter (r = -0.69, P = 0.0001), LV twist (r = 0.54, P = 0.004), LVAS (r = -0.56, P = 0.003), and RVLS (r = -0.39, P = 0.036). LVAS and AAo-CS were associated with disease severity (peak oxygen consumption and arrhythmia occurrence). Significant improvement in global χ 2 value was noted with RV 3D-STE parameters + LVAS + AAo-CS compared with RV dysfunction alone for detecting exercise capacity impairment (from 77.1 to 84.4 to 91.2, P = 0.003). Speckle-tracking echocardiography revealed subtle LV and AAo dysfunction in adults with rTOF. A correlation was observed between LV and RV strain changes and between AAo strain impairment and LV/RV dysfunction. LV and AAo changes had an incremental value in evaluating disease severity.

Predictive value of Cardiac Magnetic Resonance: new and old parameters in the natural history of repaired Tetralogy of Fallot

BackgroundPatients with repaired Tetralogy of Fallot (rTOF) often develop pulmonary regurgitation (PR) and right ventricle (RV) dysfunction, experiencing increased mortality and morbidity rates in adulthood. Pulmonary valve replacement (PVR) timing to address PR is controversial. Cardiac Magnetic Resonance (CMR) is the gold standard for morpho-functional evaluation of complex cardiopathies. This study aims to identify CMR parameters predictive of adverse outcomes to help defining the best therapeutic management of rTOF patients.Methods130 rTOF patients who underwent CMR (2006–2019) were enrolled in this retrospective single-center study. CMR, clinical, ECG and exercise data were analyzed. Univariate and multivariate analyses identified clinical and CMR parameters predictive of adverse outcomes both individually (e.g., death, arrhythmias, heart failure (HF), pharmacological therapy, QRS ≥ 160ms) and as composite outcome.ResultsUnivariate analysis confirmed RV volumes and RV ejection fraction corrected for PR as adverse outcome predictors and identified interesting correlations: pulmonary artery bifurcation geometry and abnormal interventricular septum (IVS) motion with arrhythmias (p < .001; p = .037), HF (p = .049; p = .005), composite outcome (p = .039; p = .009); right atrium (RA) dimensions with the composite outcome and the outcomes individually (p < .001). The best predictive models by multivariate analysis included sex (male), RV and RA dilation for QRS ≥ 160ms, time form repair to CMR, age at TOF repair and IVS fibrosis for pharmacological therapy.ConclusionsBesides RV volumes, new adverse prognostic factors could guide rTOF therapeutic management: pulmonary arteries morphology, abnormal IVS motion, RV dysfunction, RA dilation. Perspective multicentric evaluation is needed to specify their effective role.

Prognostic value of left atrial strain in patients with tetralogy of fallot.

To demonstrate prognostic utility of left atrial strain (LAS) in adult patients with repaired Tetralogy of Fallot (rTOF). Adults patients with rTOF were prospectively enrolled in this study between years 2011 and 2015. Left atrium (LA) phasic functions were assessed using 2D speckle tracking echocardiography. Association of LA strain (LAS) with primary (any cardiovascular event) and secondary (death, heart failure or arrhythmia) composite endpoints was assessed using Cox regression analysis. Hundred-and-twelve rTOF patients, in whom LAS was feasible and were in sinus rhythm, were included in the final analysis (age 33 ± 10years, 68[61%] male). Median duration of follow-up was 8.6 [4.2-9.7] years in the study group. Primary composite endpoint was reached in 48 patients (mean event-free survival time: 7.2 [6.6-7.9] years), and secondary composite endpoint was reached in 22 patients (mean event-free survival time: 8.7 [8.1-9.2] years). LA reservoir strain (LAS-r) was defined as tertile groups (1st tertile < 33%, 2nd tertile = 33-44%, 3rd tertile > 44%). Decreasing tertiles of LAS-r was associated with primary and secondary composite endpoints in Kaplan-Meier analysis (p = 0.02 and 0.002, respectively). In univariable Cox-regression, both decreasing LAS-r and LAS-r tertiles were associated with primary and secondary composite endpoints. Adjusted by initial repair age and NT-proBNP quartiles, increased LAS-r was associated with significantly decreased occurrence of experiencing any events (HR = 0.97, CI 0.93-0.99, p < 0.001). Decreasing LAS-r was still associated with primary endpoint when adjusted by left atrium volume index (LAVImax) (HR = 0.96, CI 0.92-0.99, p = 0.01), left ventricle global longitudinal strain (HR = 0.96, CI 0.93-0.99, p < 0.001) or right ventricle free wall longitudinal strain (HR = 0.96, CI 0.93-0.99, p = 0.03). Assessment of LA mechanics with the use of STE has incremental utility in determination of mortality and morbidity in rTOF, and may be implemented in clinical practice.

Right ventricular myocardial fibrosis evaluated by extracellular volume fraction by magnetic resonance imaging in patients with repaired tetralogy of Fallot: a meta-analysis.

The objective of this meta-analysis was to assess the clinical utility of anomalous discoveries on cardiac magnetic resonance, particularly the right ventricular extracellular volume (RV-ECV), among individuals who underwent surgical repair for Tetralogy of Fallot (rTOF). We conducted a systematic search of electronic databases including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE. Our analysis involved a comparison of ECV levels between rTOF patients and controls, as well as an evaluation of the predictive value of ECV for future adverse events. We identified 16 eligible studies that encompassed 856 rTOF patients and 283 controls. Our meta-analysis showed a significant increase in LV-ECV among rTOF patients compared to control subjects (MD = 2.63, 95%CI: 1.35 to 3.90, p < 0.0001, I2 = 86%, p for heterogeneity < 0.00001). Moreover, RV-ECV was found to be substantially higher in patients compared to LV-ECV. Our meta-analysis also revealed a significant association between RV-ECV and adverse events (HR = 1.15, 95% CI: 1.04 to 1.27, p = 0.005, I2 = 0%, p for heterogeneity = 0.62), while LV-ECV did not show any significant association with adverse events (HR = 1.12, 95% CI: 0.92 to 1.36, p = 0.16, I2 = 0%, p for heterogeneity = 0.46). The results of this meta-analysis on RV-ECV confirmed the presence of RV fibrosis as one of the prognostic factors in rTOF patients.

The R'' wave in V1 and the terminal QRS vector in aVF combine to a novel 12-lead ECG algorithm to identify slow conducting anatomical isthmus 3 in patients with tetralogy of Fallot

Abstract Background Patients with repaired tetralogy of Fallot (rTOF) have an increased risk for ventricular tachycardia (VT), with slow conducting anatomical isthmus (SCAI) 3 as the dominant VT substrate. Right bundle branch block (RBBB) is common in these patients. SCAI 3 can lead to additional activation delay affecting the terminal RV activation.(1) We hypothesize that these alterations can be detected by sinus rhythm (SR) 12-lead ECG. Purpose To develop a novel algorithm to non-invasively identify SCAI 3 with the SR 12-lead ECG in rTOF patients with RBBB. Methods Consecutive rTOF patients aged ≥16 years old with RBBB who underwent electroanatomical mapping (EAM) at our institution between 2017-2022, and 2010-2016, comprised the derivation, and validation cohort, respectively. 12-lead ECGs in SR were analyzed for presence of R’’ wave in V1 (any positive deflection after R’ in V1) and for duration of a negative terminal QRS portion (NTP) in aVF (ms between QRS complex traversing the isoelectric line from positive to negative vector until QRS offset) (Figure, A). Results Forty-six rTOF patients (aged 40±15 years, 70% male) comprised the derivation cohort. Patients were repaired at a median age of 3.3 [IQR 1.2-6.6] years via a ventricular incision in 21 (55%). Mean QRS duration was 165±23ms and 12 (26%) had a QRS duration of ≥180ms. SCAI 3 was detected in 31 (67%) patients and 15 (33%) had a normal conducting AI 3. Monomorphic sustained VT was inducible in 16 (35%). Among patients with SCAI 3, 17 (55%), and 16 (52%), had an R’’ in V1, and NTP ≥80ms in aVF, respectively, compared to only 1 (7%), and 1 (7%) patients with normal conducting AIs. Of the 24 patients with an R’’ in V1 and/or NTP ≥80ms in aVF, 22 (92%) had a SCAI 3. In univariable analysis an R’’ in V1 had an odds ratio (OR) of 17.0 (p=0.010), a NTP ≥80ms in aVF had an OR of 14.9 (p=0.014), and QRS duration had an OR of 1.04 (per ms, p=0.030) in identifying SCAI 3. After correction for QRS duration, R’’ in V1 and NTP ≥80ms in aVF both remained independently predictive of SCAI 3 (OR 15.4, p=0.017, and OR 10.0, p=0.042, respectively). Combining R’’ in V1 and NTP ≥80ms in aVF into a diagnostic algorithm (Figure, B) yielded a sensitivity of 71% and specificity of 87% in detecting SCAI 3. In the validation cohort (n=34, age 44±14 years, 19 (56%) with SCAI 3 and 15 (44%) with normal conducting AI 3) the diagnostic algorithm had a sensitivity of 84% and specificity of 80% for a SCAI. Conclusion A diagnostic algorithm including R’’ in V1 and NTP ≥80ms in aVF had excellent sensitivity and specificity in detecting SCAI 3 in rTOF patients with RBBB in SR. These ECGs characteristics likely represent a delayed terminal RV activation directed towards the lateral RVOT caused by slow infundibular conduction. Whether this algorithm can contribute to non-invasive risk stratification for VT in a general rTOF population requires additional studies.Diagnostic algorithm to identify SCAI 3

Predictors of clinical outcome in adults with repaired tetralogy of Fallot and the prognostic value of surrogate markers of right ventricular dyssynchrony

Abstract Introduction Sequelae or residual lesions after surgical repair of tetralogy of Fallot (rTOF) are inevitable and have an impact on long-term outcome. So far, most of our attention was directed to negative consequences of residual pulmonary regurgitation. Less attention has been paid to the impact of right bundle branch block and intraventricular dyssynchrony on biventricular function, exercise capacity and clinical outcome. Purpose Using the Swiss Adult Congenital HEart disease Registry we aimed to investigate the 5-year clinical course of adults with rTOF late after surgical repair. We used echocardiography strain analysis as surrogate to quantify right and left ventricular dyssynchrony and correlated our findings with routine clinical measures from cardiopulmonary exercise testing, neurohumoral blood work and cardiac magnetic resonance imaging with the aim to identify patients at increased risk for an adverse clinical event. Methods 2D speckle-tracking strain analysis of the right and left ventricle was performed with dedicated software (Tomtec, Germany). RV dyssynchrony index was measured as the standard deviation of time to peak shortening (TTP) in six RV segments. Interventricular shortening delay (IVSD) was defined as the maximal delay of TTP between ventricular segments. We constructed a multivariate model with NT-proBNP, ECG, clinical, imaging and exercise testing variables to predict the composite outcome of all-cause mortality, relevant arrhythmias and hospital admission for decompensated heart failure. Results A total of 285 patients were included. During a mean follow-up of 48±21 months, 33 patient (12 %) suffered an adverse event with a mean time to event of 30 ± 21 months after the baseline visit. RV dyssynchrony index and IVSD did not differ statistically between the groups with and without events (49±31ms vs 41±18ms, p-value 0.21, 130±65ms vs. 103±50ms, p-value 0.9). In the multivariate Cox-regression model, NT-proBNP, right atrial area and peak heart rate at exercise testing were independent predictors of outcome. An integrated risk score with the median values of these 3 variables as cut-off was highly accurate in separating patients at low risk (score 0; n=39) and high risk (score 3; n=38) for an adverse event. After 6 years of follow-up, no patient at low risk (score 0) had an adverse event, while in 62% of patients at high risk (score 3) an adverse event occurred (p&amp;lt;0.001). Conclusion In our cohort of rTOF patients, echocardiographic surrogates of RV dyssynchrony did not correlate with clinical events. An integrated multimodality approach proved to be effective in predicting outcomes.

External validation of survival predicting score in repaired tetralogy of Fallot: an opportunity to improve

Abstract Introduction In recent years, integrating both better diagnosis and treatment allowed most adults with repaired tetralogy of Fallot (rTOF) to expect a longer life expectancy. However, a minority is at higher risk for premature cardiovascular death. Recently, 2 scores identified the subgroup of rTOF patients (pts) who are at high annual risk of death and ventricular arrhytmias (VA). We aimed to implement both in our population. Methods Retrospective single center review was done on rTOF pts who undergone cardiovascular magnetic resonance with gadolinium, blood sampling for B-type natriuretic peptide (BNP), echocardiography and cardiopulmonary exercise testing. The risk scores were calculated with weighted independent predictors, namely presence of late gadolinium enhancement in left ventricle (LV) and right ventricle (RV), akinetic RV outflow length, LV and RV ejection fraction (EF), RV systolic pressure, peak oxygen uptake (pVO2), BNP, atrial arrythmias and age. Low mortality risk was defined as 0-20 points, intermediate as 21-50 and high ≥51. In terms of VA prediction, low risk was defined as 0-20 points, intermediate as 21-39 and high as ≥51. Results From a total of 240 rTOF pts, 61 (56% male, mean age 34±9 years) had all the necessary data. RV dysfunction was present in 52.5%, RV systolic pressure was high in 12 and LVEF≤35% in 18% pts. BNP level was elevated in 27 and pVO2≤17mL/kg/m2 in 14.8% pts. The mean mortality risk score was 15.1±11.2, being that 68.9% had a lower and 31.1% an intermediate risk. Regarding VA score, the mean was 14.7±10.8, where the majority (80.3%) were in lower risk. 29.5% had a sustain atrial arrhythmia (mainly atrial fibrillation) and 14.8% a VA. There were 3 cardiac related deaths (4.9%). Analysis of time to event data showed that mortality and VA scores were not predictors of overall mortality (M) or VA events, respectively. However, considering 1-year M, LVEF≤35% (p= 0.002), RVEF≤35% (p=0.002), pVO2≤17mL/kg/m2 (p&amp;lt;0.001), and both scores: M (p=0.013) and VA (p&amp;lt;0.001) were predictors of that endpoint. In multivariate analysis, VA risk score (p=0.035) and low pVO2 (p= 0.006) were independent 1-year M predictors. Conclusion In our population, ventricular arrhythmia score and low peak oxygen uptake were independent predictors of 1-year mortality. However, there is probably a selection bias. Since the scores were recently proposed, patients were not recruited prospectively, many ended up not having all the needed or recent data, thus were not included. There is the need to validate and improve available scores to truly assess the risk of mortality and arrhythmias, as well as defined protocols and longer follow-up for this purpose.

Abstract 14833: Association of RV Hemodynamics From 4D Flow CMR With RV Restrictive Physiology From Pediatric to Adult Repaired Tetralogy of Fallot

Introduction: Right ventricular restrictive physiology (RVRP) is common after repair of Tetralogy of Fallot (rTOF), especially with residual pulmonary regurgitation. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) quantitates biventricular blood flow components and kinetic energy (KE) parameters, but their association with RVRP is unclear. We aimed to study 4D flow CMR parameters in adult and pediatric rTOF patients vs healthy controls and associations of 4D flow parameters with RVRP in rTOF. Methods: 103 rTOF patients (40 pediatric, 63 adult; age 24±17 years; 53M:50F) and 171 healthy controls (14 pediatric, 157 adult; age 40±15 years; 97M:74F) were prospectively recruited from centers in Singapore (2) and China (1) to undergo 4D flow CMR on multi-vendor scanners. LV and RV flow components—direct flow, retained inflow, delayed ejection flow and residual volume—and KE parameters (normalized to end-diastolic volume, KEi EDV )—global, peak systolic, average systolic, average diastolic, peak E-wave and peak A-wave—were analyzed. KE discordance was calculated as the ratio of RV and LV average systolic KEi EDV . Results: See Table. RVRP was identified in 70 patients (68%). rTOF with RVRP exhibited higher median RV stroke volume index, RV ejection fraction, RV direct flow, RV peak E-wave and E-wave/A-wave, and lower RV residual volume compared to rTOF without RVRP (all P&lt;0.05). Using binary multivariable logistic regression analysis—and after adjustment for age, pulmonary regurtitation, LV and RV ejection fraction, RV direct flow was found to be independently associated with RVRP in rTOF (P&lt;0.001). Conclusion: Patients with RVRP had higher RV direct flow, RVEF and RV peak E-wave energy, indicating the potential compensatory adaptations in patients with RVRP.

Abstract 12854: Early and Late Features of Intracardiac Flow in Repaired Tetralogy of Fallot (rTOF) Patients Using Doppler Velocity Reconstruction (DoVeR)

Background: Intracardiac flow analysis has implicated flow energy loss (FEL), kinetic energy (KE) and vortex strength (VS) as markers of ventricular dysfunction in repaired Tetralogy of Fallot (TOF); no studies have investigated early vs. late intracardiac flow conditions after repair. We utilized novel echocardiography (echo) based Doppler Velocity Reconstruction (DoVeR) to determine FEL, KE and VS in pre-operative TOF vs early post-repair (&lt;1 month) and late post-repair (&gt;10 years). Methods: This was a single-center retrospective cross-sectional study on TOF patients with pre- and post-operative surveillance transthoracic echo. Apical 4 chamber color Doppler views were collected. The streamfunction-vorticity formulation was used to reconstruct left ventricular (LV) blood velocity fields by DoVeR. Velocity flow fields were evaluated for peak FEL, KE and VS. The FEL was also normalized against KE to account for physiologic variations. Data were compared via one-way ANOVA. Results: Echo studies from 14 pre-operative (1.7±0.5 months), 14 early-post repair (3.6±2.3 months) and 15 late-post repair (16.5±6.6 years) TOF patients were included. There was significant variation in FEL, KE, VS, and normalized FEL across timepoints (all p&lt;0.05) (Figure B). In general, when compared to pre-operative TOF, the early post-repair cohort had lower FEL/KE/VS corresponding to reduction in ventricular volume load; however late post-repair cohort had higher FEL/KE/VS, suggestive of effects from long-term interventricular interactions. Conclusion: The LV intracardiac flow in TOF changes early after initial repair and late after repair. DoVeR could potentially be used to serially evaluate TOF patients.

Right-Left Ventricular Interdependence in Repaired Tetralogy of Fallot Patients With Right Ventricular Heart Failure.

Patients with repaired tetralogy of Fallot (rTOF) continue to face a heightened risk of deteriorating cardiac function, and quantitative techniques of cardiac MRI-derived cardiac structure and function provide an opportunity to explore the causes and mechanisms of cardiac deterioration. To explore right-left ventricular interdependence in rTOF patients before and after the onset of right ventricular (RV) heart failure. Retrospective. One hundred eighteen rTOF patients (21.85 [16.74, 29.20] years, 58 females) and 34 controls (23.5 [21, 26.5] years, 17 females) that underwent cardiac MRI were analyzed, with rTOF patients being further subdivided into those with preserved RV function (N = 54) and those that experienced RV heart failure (N = 64). 3.0 T/balanced steady-state free precession sequence. RV, left ventricular (LV), and septal strain; RV and LV volume. Chi-squared tests or Fisher's exact test, One-way ANOVAs with Bonferroni's post hoc test, Pearson/Spearman correlation, and multivariate backward linear regression analysis. A two-tailed P < 0.05 was deemed as the significance threshold. The MRI-derived RV, LV, and septal strain decreased sequentially in controls, patients with preserved RV function, and patients with RV heart failure, with a good intra-observer (0.909-0.964) and inter-observer (0.879-0.937) agreement. Correlations between LV and RV strain were found to change sequentially with RV function and were the closest in rTOF patients with RV heart failure (r = -0.270 to 0.506). Correlations between RV volume and septal strain was variable in controls (r = 0.483 to -0.604), patients with preserved RV function (r = -0.034 to -0.295), and patients with RV heart failure (r = -0.026 to 0.500). Multivariate analyses revealed that the RV longitudinal strain was independently correlated with LV strain in three directions in rTOF patients with RV heart failure (Radial -0.70 [-1.33, -0.06]; Circumferential 0.44 [0.17, 0.72]; Longitudinal 0.54 [0.26, 0.81]). In rTOF patients, the coupling between RV volume and septal strain was broken during RV function compensation, and the adverse effect of RV on LV deformation was highest in patients with RV heart failure. 4 TECHNICAL EFFICACY: Stage 5.

Right ventricular dilatation score: a new assessment to right ventricular dilatation in adult patients with repaired tetralogy of Fallot

BackgroundPatients with repaired tetralogy of Fallot (rTOF) experience long-term chronic pulmonary valve regurgitation resulting in right ventricular (RV) dilatation. According to current guidelines, the evaluation of patients with rTOF for RV dilatation should be based on cardiac magnetic resonance (CMR). However, for many asymptomatic patients, routine CMR is not practical. Our study aims to identify screening methods for CMR based on echocardiographic data, with the goal of establishing a more practical and cheap method of screening for severity of RV dilatation in patients with asymptomatic rTOF.MethodsThirty two rTOF patients (mean age, 21(10.5) y, 21 males) with moderate to severe pulmonary regurgitation (PR) were prospectively recruited. Each patient received CMR and echocardiogram examination within 1 month prior to operation and collected clinical data, and then received echocardiogram examination at discharge and 3–6 months post-surgery.ResultsRV moderate-severe dilatation was defined as right ventricular end-diastolic volume index (RVEDVI) ≥ 160 ml/m2 or right ventricular end-systolic volume index (RVESVI) ≥ 80 ml/m2 in 15 of 32 patients (RVEDVI, 202.15[171.51, 252.56] ml/m2, RVESVI, 111.99 [96.28, 171.74] ml/m2). The other 17 (RVESDI, 130.19 [117.91, 139.35] ml/m2, RVESVI = 67.91 [63.35, 73.11] ml/m2) were defined as right ventricle mild dilatation, i.e., RVEDVI < 160 ml/m2 and RVESVI < 80 ml/m2, and the two parameters were higher than normal values. Compared with the RV mild dilatation group, patients of RV moderate-severe dilatation have worse cardiac function before surgery (right ventricular ejection fraction, 38.92(9.19) % versus 48.31(5.53) %, p < 0.001; Left ventricular ejection fraction, 59.80(10.26) versus 66.41(4.15), p = 0.021). Patients with RV moderate-severe dilatation faced longer operation time and more blood transfusion during operation (operation time, 271.53(08.33) min versus 170.53(72.36) min, p < 0.01; Intraoperative blood transfusion, 200(175) ml versus 100(50) ml, p = 0.001). Postoperative RV moderate-severe dilatation patients have poor short-term prognosis, which was reflected in a longer postoperative hospital stay (6.59 [2.12] days versus 9.80 [5.10] days, p = 0.024) and a higher incidence of hypohepatia (0[0] % versus 4[26.7] %, p = 0.023). Patients with RV dilatation score > 2.35 were diagnosed with RV moderate-severe dilatation (AUC = 0,882; Sensitivity = 94.1%; Specificity = 77.3%).ConclusionsRV moderate-severe dilatation is associated with worse preoperative cardiac function and short-term prognosis after PVR in rTOF patients with moderate to severe PR. The RV dilatation score is an effective screening method. When RV dilatation score > 2.35, the patient is indicated for further CMR examination and treatment.