Integrated multi-omic characterization of congenital heart disease.

The heart, the first organ to develop in the embryo, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of patients with CHD survive into adulthood, but many suffer premature death from heart failure and non-cardiac causes1. Here, to gain insight into this disease progression, we performed single-nucleus RNA sequencing on 157,273 nuclei from control hearts and hearts from patients with CHD, including those with hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot, two common forms of cyanotic CHD lesions, as well as dilated and hypertrophic cardiomyopathies. We observed CHD-specific cell states in cardiomyocytes, which showed evidence of insulin resistance and increased expression of genes associated with FOXO signalling and CRIM1. Cardiac fibroblasts in HLHS were enriched in a low-Hippo and high-YAP cell state characteristic of activated cardiac fibroblasts. Imaging mass cytometry uncovered a spatially resolved perivascular microenvironment consistent with an immunodeficient state in CHD. Peripheral immune cell profiling suggested deficient monocytic immunity in CHD, in agreement with the predilection in CHD to infection and cancer2. Our comprehensive phenotyping of CHD provides a roadmap towards future personalized treatments for CHD.

Three-dimensional cardiac magnetic resonance allows the identification of slow-conducting anatomical isthmuses in tetralogy of Fallot.

BACKGROUND AND AIMS: Patients 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). METHODS: Consecutive 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. RESULTS: The 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). CONCLUSIONS: 3D 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.

The effects of pregnancy in subjects with repaired tetralogy of Fallot.

BACKGROUND: Previous reports reveal inconsistent findings of right ventricular (RV) changes following pregnancy in subjects with repaired tetralogy of Fallot (rTOF). METHODS: A two-center, retrospective cohort study which included women with rTOF who completed pregnancy that were matched to nulliparous women with rTOF by age at the time of baseline cardiac magnetic resonance (CMR), RV ejection fraction (RVEF), and indexed RV end-diastolic volume (RVEDVi). Pre-pregnancy and postpartum cardiac magnetic resonance (CMR) were analyzed and compared to sequential CMR of nulliparous subjects with rTOF. RESULTS: Thirty-six women with rTOF who completed pregnancy were matched to 72 nulliparous women with rTOF. Over a mean period of 3.1 years for the pregnancy group and 2.7 years for the comparison group, there was no significant change in the RVEDVi, RVEF, RV mass, pulmonary regurgitation severity, left ventricular (LV) volumes, LV ejection fraction (LVEF), or LV mass when comparing the baseline CMR and the follow-up CMR in either of the groups. There was a slight increase in RV indexed end-systolic volume (RVESVi) when comparing the baseline CMR and the follow-up CMR in the pregnancy group (68.93, SD 23.34 ml/m2 at baseline vs. 72.97, SD 25.24 mL/m2 at follow-up, P = .028). Using a mixed effects model for CMR parameters change over time; when adjusted for time between baseline and follow-up CMR there was no significant difference in rate of change between the pregnancy and comparison groups. CONCLUSIONS: Most ventricular remodeling parameters measured by CMR did not significantly change in subjects with rTOF who completed pregnancy or in nulliparous subjects with rTOF. In the pregnancy group, RVESVi is larger in those individuals who have undergone pregnancy without a significant change in ventricular function. These patients should be followed longitudinally to determine the long-term ventricular and clinical effects of pregnancy.

De novo start-loss variant in HIRA in patient with DiGeorge-like syndrome.

A case of a newborn with tetralogy of Fallot, corpus callosum hypoplasia, and phenotypic features similar to DiGeorge syndrome. Chromosomal microarray analysis did not reveal any alterations. Whole exome sequencing and Sanger sequencing identified a de novo variant in the HIRA gene resulting in the loss of the start codon.

Recent advances in multimodal imaging in tetralogy of fallot and double outlet right ventricle.

PURPOSE OF REVIEW: In the ever-evolving field of medical imaging, this review highlights significant advancements in preoperative and postoperative imaging for Tetralogy of Fallot (TOF) and double outlet right ventricle (DORV) over the past 18 months. RECENT FINDINGS: This review showcases innovations in echocardiography such as 3D speckle tracking echocardiography (3DSTE) for assessing right ventricle-pulmonary artery coupling (RVPAC) and Doppler velocity reconstruction (DoVeR) for intracardiac flow fields evaluation. Furthermore, advances in assessment of cardiovascular anatomy using computed tomography (CT) improve the integration of imaging in ablation procedures. Additionally, the inclusion of cardiac magnetic resonance (CMR) parameters as risk score predictors for morbidity, and mortality and for timing of pulmonary valve replacement (PVR) indicates its significance in clinical management. The utilization of 4D flow techniques for postoperative hemodynamic assessment promises new insights into pressure mapping. Lastly, emerging technologies such as 3D printing and 3D virtual reality are expected to improve image quality and surgical confidence in preoperative planning. SUMMARY: Developments in multimodality imaging in TOF and DORV are poised to shape the future of clinical practice in this field.

Transcatheter pulmonary valve replacement in surgically-created double-barrel right ventricular outflow tracts: A single center case-series.

This manuscript describes the feasibility and approach to the assessment and performance of transcatheter pulmonary valve replacement (tPVR) in patients with surgically-created "double-barrel" right ventricular outflow tracts (RVOT). Patients with tetralogy of Fallot may have coronary anomalies which prohibit the performance of traditional tetralogy of Fallot repair. In certain cases, this may necessitate the placement of a right ventricle to pulmonary artery conduit in addition to the native RVOT, which is left in situ, creating so-called "double-barrel" RVOTs. When these patients develop RVOT dysfunction later in life, they would typically be referred for reoperation due to concerns for risk of coronary compression associated with a transcatheter approach. However, whether a transcatheter approach with valve replacement in the native RVOT is feasible or safe is unknown. This was a retrospective review of patients with a surgically created "double-barrel" RVOTs who underwent cardiac catheterization for assessment of tPVR at Boston Children's Hospital. From July 2012 to July 2022, there were four patients with "double-barrel" RVOTs who underwent assessment for tPVR. The age at catheterization ranged between 22 and 39 years. In three out of four patients, coronary compression testing was negative. These three patients had successful tPVR in the native RVOT. At follow up, all three patients were free of greater than mild regurgitation by echocardiogram and had a maximum instantaneous gradient across the RVOT ranging between 20 and 33 mmHg. Performance of tPVR in patients with surgically created "double-barrel" RVOTs is feasible. The safety of this procedure depends crucially on coronary artery assessment at all stages.

Growth of the right ventricular outflow tract in repaired tetralogy of Fallot: A longitudinal CMR study.

BACKGROUND: Many patients with repaired tetralogy of Fallot require pulmonary valve replacement (PVR) due to significant pulmonary regurgitation (PR). Transcatheter PVR (TPVR) is an equally effective and less invasive alternative to surgical PVR but many native right ventricular outflow tracts (RVOTs) are too large for TPVR at time of referral. Understanding the rate of growth of the RVOT may help optimize timing of referral. This study aims to examine the longitudinal growth of the native RVOT over time in repaired tetralogy of Fallot (TOF). METHODS: A retrospective review of serial cardiac MRI cardiovascular magnetic resonance (CMR) data from 121 patients with repaired TOF and a native RVOT (median age at first CMR 14.7 years, average interval between the first and last CMR of 8.1 years) was performed to measure serial changes in RVOT diameter, cross-sectional area, perimeter-derived diameter, and length. RESULTS: All parameters of RVOT size continued to grow with increasing age but growth was more rapid in the decade after TOF repair (for minimum systolic diameter, mean increase of 5.7 mm per 10 years up to year 12, subsequently 2.3 mm per 10 years). The RVOT was larger with a transannular patch and in patients without pulmonary stenosis (p < 0.001 for both), but this was not associated with rate of growth. More rapid RVOT enlargement was noted in patients with larger right ventricular end-diastolic volume (RVEDV), higher PR fraction, and greater rates of increases in RVEDV and PR (p < 0.001 for all) CONCLUSIONS: in patients with repaired TOF, using serial CMR data, we found that RVOT size increased progressively at all ages, but the rate was more rapid in the first decade after repair. More rapid RVOT enlargement was noted in patients with a larger RV, more PR, and greater rates of increases in RV size and PR severity. These results may be important in considering timing of referral for transcatheter pulmonary valves, in planning transcatheter and surgical valve replacement, and in designing future valves for the native RVOT.

Automated isochronal late activation mapping for substrate characterization in patients with repaired tetralogy of Fallot.

AIMS: Slow conduction (SC) anatomical isthmuses (AIs) are the dominant substrate for monomorphic ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot (rTF). This study aimed to evaluate the utility of automated propagational analysis for the identification of SC-AI in patients with rTF. METHODS AND RESULTS: Consecutive rTF patients undergoing VT substrate characterization were included. Automated isochronal late activation maps (ILAM) were obtained with multielectrode HD Grid Catheter. Identified deceleration zones (DZs) were compared with both SC-AI defined by conduction velocity (CV) (<0.5 m/s) and isthmuses of induced VT for mechanistic correlation. Fourteen patients were included (age 48; p25-75 35-52 years; 57% male), 2 with spontaneous VT and 12 for risk stratification. Nine VTs were inducible in seven patients. Procedure time was 140 (p25-75 133-180) min and mapping time 29.5 (p25-75 20-37.7) min, using a median of 2167 points. All the patients had at least one AI by substrate mapping, identifying a total of 27 (11 SC-AIs). Isochronal late activation maps detected 10 DZs mostly in the AI between ventricular septal defect and pulmonary valve (80%). Five patients had no DZs. A significant negative correlation between number of isochrones/cm and CV was observed (rho -0.87; P < 0.001). Deceleration zones correctly identified SC-AI (90% sensitivity; 100% specificity; 0.94 accuracy) and was related to VT inducibility (P = 0.006). Deceleration zones co-localized to the critical isthmus of induced VTs in 88% of cases. No complications were observed. CONCLUSION: Deceleration zones displayed by ILAM during sinus rhythm accurately identify SC-AIs in rTF patients allowing a safe and short-time VT substrate characterization procedure.

How to assess and treat right ventricular electromechanical dyssynchrony in post-repair tetralogy of Fallot: insights from imaging, invasive studies, and computational modelling.

BACKGROUND AND AIMS: Right bundle branch block (RBBB) and resulting right ventricular (RV) electromechanical discoordination are thought to play a role in the disease process of subpulmonary RV dysfunction that frequently occur post-repair tetralogy of Fallot (ToF). We sought to describe this disease entity, the role of pulmonary re-valvulation, and the potential added value of RV cardiac resynchronization therapy (RV-CRT). METHODS: Two patients with repaired ToF, complete RBBB, pulmonary regurgitation, and significantly decreased RV function underwent echocardiography, cardiac magnetic resonance, and an invasive study to evaluate the potential for RV-CRT as part of the management strategy. The data were used to personalize the CircAdapt model of the human heart and circulation. Resulting Digital Twins were analysed to quantify the relative effects of RV pressure and volume overload and to predict the effect of RV-CRT. RESULTS: Echocardiography showed components of a classic RV dyssynchrony pattern which could be reversed by RV-CRT during invasive study and resulted in acute improvement in RV systolic function. The Digital Twins confirmed a contribution of electromechanical RV dyssynchrony to RV dysfunction and suggested improvement of RV contraction efficiency after RV-CRT. The one patient who underwent successful permanent RV-CRT as part of the pulmonary re-valvulation procedure carried improvements that were in line with the predictions based on his Digital Twin. CONCLUSION: An integrative diagnostic approach to RV dysfunction, including the construction of Digital Twins may help to identify candidates for RV-CRT as part of the lifetime management of ToF and similar congenital heart lesions.

Risk Factors for Coronary Artery Complications After Prosthetic Pulmonary Valve Implantation in Patients With Congenital Heart Disease.

BACKGROUND: Coronary artery complications (CACs) in patients who undergoing prosthetic pulmonary valve implantation for congenital heart disease can lead to fetal outcomes. However, the incidence of and risk factors for CACs in these patients remain unknown.Methods and Results: A retrospective cohort study was conducted on patients who underwent cardiac computed tomography or invasive coronary angiography after prosthetic pulmonary valve implantation at Seoul National University Hospital from June 1986 to May 2021. Among 341 patients, 25 (7.3%) were identified with CACs, and 2 of them died. Among the patients with CACs, congenital coronary anomalies and an interarterial course of the coronary artery were identified in 11 (44%) and 18 (72%) patients, respectively. Interarterial and intramural courses of the coronary artery were associated with a 4.4- and 10.6-fold increased risk of CACs, respectively. Among patients with tetralogy of Fallot and pulmonary atresia, the aortic root was rotated further clockwise in patients with coronary artery compression compared to those without it (mean [±SD] 128.0±19.9° vs. 113.5±23.7°; P=0.024). The cut-off rotation angle of the aorta for predicting the occurrence of coronary artery compression was 133°. CONCLUSIONS: Perioperative coronary artery evaluation and prevention of CACs are required in patients undergoing prosthetic pulmonary valve implantation, particularly in those with coronary artery anomalies or severe clockwise rotation of the aortic root.

Primary surgical repair of tetralogy of fallot at the Uganda Heart Institute: a ten-year review of 30day mortality and morbidity.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease (CHD) worldwide. It accounts for 7% of CHD cases in Uganda and leads to fatal outcomes in the long term without surgery. Surgery is often delayed in developing countries like Uganda due to limited resources. OBJECTIVE: This study aimed to determine the early surgical outcomes of patients with TOF who underwent primary intracardiac repair at the Uganda Heart Institute (UHI) and to identify factors associated. METHODOLOGY: This retrospective chart review evaluated outcomes of primary TOF repair patients at UHI from February 2012 to October 2022. Patient outcomes were assessed from surgery until 30 days post-operation. RESULTS: Out of the 104 patients who underwent primary TOF repair at UHI, records of 88 patients (84.6%) were available for review. Males accounted for 48.9% (n = 43). The median age at the time of operation was 4 years (with an interquartile range of 2.5-8.0 years), ranging from 9 months to 16 years. Genetic syndromes were present in 5/88 (5.7%). These included 2 patients with trisomy 21, 2 with Noonan's, and 1 with 22q11.2 deletion syndrome. Early postoperative outcomes for patients included: residual ventricular septal defects in 35/88 (39.8%), right ventricular dysfunction in 33/88 (37.5%), residual pulmonary regurgitation in 27/88 (30.7%), residual right ventricular outflow tract obstruction in 27/88 (30.0%), pleural effusion in 24/88 (27.3%), arrhythmias in 24/88(27.3%), post-operative infections in 23/88(26.1%) and left ventricular systolic dysfunction in 9/88 (10.2%). Out of the children who underwent surgery after one year of age, 8% (7 children) died within the first 30 days. There was a correlation between mortality and post-operative ventilation time, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, preoperative oxygen saturations, RV and LV dysfunction and the operating team. CONCLUSION: The most frequent outcomes after surgery were residual ventricular septal defects and right ventricular failure. In our study, the 30-day mortality rate following TOF repair was 8%. Deceased patients had lower pre-operative oxygen levels, longer CPB and cross-clamp times, longer post-operative ventilation, RV/LV dysfunction, and were more likely operated by the local team.

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

BACKGROUND: Patients 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. METHODS: 130 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. RESULTS: Univariate 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. CONCLUSIONS: Besides 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.

Aveir retrievable, 38-mm length, leadless pacemaker implantation in a 23-kg pediatric patient with congenital heart disease.

INTRODUCTION: Complications are more prevalent in pediatric patients receiving pacemaker implants. METHODS: We performed a retrospective review of a retrievable, 38 mm leadless pacemaker implantation in a 23-kg pediatric patient. CASE/DISCUSSION: An active 9-year-old, 23 kg male patient with tetralogy of Fallot with intermittent pacing need presented with a fractured lead and pacing need. He underwent implant of a retrievable leadless pacemaker (Abbott Aveir) via internal jugular vein access, without complication, and with echocardiographic guidance. His threshold was stable at 1.25 V @0.4 ms, with stable impedance and sensing at 5-month follow-up. CONCLUSION: Aveir retrievable leadless pacemakers can be implanted safely in a child with tetralogy of Fallot, as small as 23 kilograms.

Association of right aortic arch and agenesis of ductus arteriosus in prenatal tetralogy of Fallot spectrum and its clinical implications.

OBJECTIVE: In our center, we observed an increased frequency of right aortic arch (RAA) with an agenesis of the ductus arteriosus (ADA) in prenatally diagnosed tetralogy of Fallot (ToF) and its variations. This study aimed to determine whether there is an association of RAA and ADA in fetuses with ToF. Distribution of genetic anomalies and impact on postnatal outcome were further evaluated. METHOD: Single-center retrospective observational study including pregnancies with prenatal diagnosis of ToF from 2010 to 2023. All cases were subdivided into ToF with pulmonary stenosis (PS) and pulmonary atresia (PA). Clinical and echocardiographic databases were reviewed for pregnancy outcome, genetic anomalies, and postnatal course. RESULTS: The cohort included 169 cases, 124 (73.4%) with ToF/PS and 45(26.6%) with ToF/PA. Agenesis of the ductus arteriosus was significantly associated with RAA in both subtypes of ToF (p = 0.001) compared to left aortic arch and found in 82.5% (33/40) versus 10.7% (9/84) of fetuses with ToF/PS and in 57.1% (8/14) versus 12.9% (4/31) of fetuses with ToF/PA. In both ToF/PS and ToF/PA, RAA/ADA versus RAA/patent DA revealed a significantly higher risk for the presence of genetic abnormalities, especially microdeletion 22q11.2, major aorto-pulmonary collateral arteries and a shorter time to complete surgical repair. CONCLUSION: We demonstrated a significantly increased frequency of RAA/ADA in patients with prenatally diagnosed ToF. Although this association revealed no significant impact on overall survival, the prenatal detection of RAA/ADA has implications for counseling, genetic evaluation and postnatal management.

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

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: The results of this meta-analysis on RV-ECV confirmed the presence of RV fibrosis as one of the prognostic factors in rTOF patients.

Flow pattern analysis of right ventricular outflow tract in repaired tetralogy of Fallot through 4D flow MRI.

Cardiac magnetic resonance imaging (CMR) often shows discrepancies between right ventricular outflow tract (RVOT) flow and left ventricular outflow tract flow in patients with late-stage repaired tetralogy of Fallot (rTOF), leading to potential errors in pulmonary regurgitation fraction (PRF) assessment. This study aimed to identify the conditions under which RVOT flow can be acutely evaluated using four-dimensional (4D) flow CMR. Twenty-seven consecutive patients with rTOF underwent both two-dimensional phase-contrast (2D PC) and 4D flow CMR between 2016 and 2018, excluding those with peripheral pulmonary artery stenosis, RVOT conduit replacement, unknown surgical method, and an aortic valve regurgitation greater than 20%. Seven healthy controls also underwent only 4D Flow CMR. All healthy controls and fifteen patients with rTOF showed laminar RVOT flow, while seven patients exhibited helical, and four patients exhibited vortical RVOT flow in 4D flow CMR visualization. Flow-volume concordance between the pulmonary artery and aortic flow was significantly lower in patients with rTOF and PRF > 40% in 2D PC CMR. This concordance rate in the suprapulmonary valve was high in both the TOF and control groups, comparing at five RVOT locations in 4D flow CMR. Regarding RVOT flow regurgitation in 4D flow, the whole bulk evaluation exhibited greater variation depending on the flow type compared to the whole pixel-wise evaluation. The study confirmed the flow volume at the upper section of the pulmonary valve as the most accurate correlate of aortic flow volume. Furthermore, the 4D flow CMR using the pixel-wise method demonstrated superior accuracy compared to the traditional bulk flow method.

The Ongoing Debate: Longevity of Biological Valves in Pulmonary Position.

BACKGROUND: In patients with tetralogy of Fallot (ToF) or ToF-like anatomy, factors possibly impacting the longevity of biological valves in the pulmonary position were investigated. METHOD: Between 1997 and 2017, 79 consecutive hospital survivors with a median age of 8.7 years (range: 0.2-56.1 years; interquartile range [IQR]: 14.8 years) with ToF or ToF-like anatomy underwent surgical implantation of Contegra (n = 34), Hancock (n = 23), Perimount (n = 9), pulmonary homograft (n = 9), and miscellaneous (n = 4) conduits. The median internal graft diameter was 19 mm (range: 11-29 mm; IQR: 8 mm) which refers to a median z-score of 0.6 standard deviation (SD) (range: -1.8 to 4.0 SD; IQR: 2.1 SD). RESULTS: The median time of follow-up was 9.4 years (range: 1.1-18.8 years; IQR: 6.0 years). Thirty-nine patients (49%) underwent surgical (n = 32) or interventional (n = 7) pulmonary valve re-replacement. Univariate Cox regression revealed patient age (p = 0.018), body surface area (p = 0.004), internal valve diameter (p = 0.005), and prosthesis z-score (p = 0.018) to impact valve longevity. Multivariate Cox regression analysis, however, did not show any significant effect (likely related to multicollinearity). Subgroup analysis showed that valve-revised patients have a higher average z-score (p = 0.003) and younger average age (p = 0.007). CONCLUSION: A decreased longevity of biological valves in the pulmonary position is related to younger age, lower valve diameter, and higher z-score. Because valve size (diameter and z-score) can be predicted by age, patient age is the crucial parameter influencing graft longevity.

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

BACKGROUND: 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). METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Huge congenital right ventricular diverticulum in tetralogy of Fallot with pulmonary atresia: A double trouble.

Congenital diverticulum is an uncommonly detected cardiac lesion, especially in infancy. However, its association with cyanotic congenital heart disease is extremely rare. In the current work, we report a case diagnosed in the neonatal period with tetralogy of Fallot and pulmonary valve atresia associated with a large congenital diverticulum originating from the right ventricle.

Effectiveness of Dexmedetomidine as Myocardial Protector in Children With Classic Tetralogy of Fallot Having Corrective Surgery: A Randomized Controlled Trial.

OBJECTIVES: Efficacy of dexmedetomidine (DEX) as a cardioprotective agent in Indonesian children undergoing classic tetralogy of Fallot (TOF) repair with cardiopulmonary bypass (CPB). DESIGN: A prospective, parallel trial using block randomization along with double-blinded preparation of treatment agents by other parties. SETTING: National Cardiovascular Center Harapan Kita, Indonesia. PARTICIPANTS: Sixty-six children with classic TOF scheduled for corrective surgery. No children were excluded. All patients had fulfilled the criteria for analysis. INTERVENTIONS: A total of 0.5 µg/kg bolus of DEX was added to the CPB priming solution, followed by 0.25 µg/kg/h maintenance during bypass. The placebo group used normal saline. Follow-ups were up to 30 days. MEASUREMENTS AND MAIN RESULTS: Troponin I was lower in the DEX group at 6 hours (30.48 ± 19.33 v 42.73 ± 27.16, p = 0.039) and 24 hours after CPB (8.89 ± 5.42 v 14.04 ± 11.17, p = 0.02). Within a similar timeframe, DEX successfully lowered interleukin-6 (p = 0.03; p = 0.035, respectively). Lactate was lower in the Dex group at 1, 6, and 24 hours after CPB (p < 0.01; p = 0.048; p = 0.035; respectively). Dexmedetomidine increased cardiac output and index from 6 hours after bypass, but vice versa in systemic vascular resistance. Reduction of vasoactive inotropic score was seen during intensive care unit monitoring in the Dex group (p = 0.049). Nevertheless, DEX did not significantly affect the length of ventilation (p = 0.313), intensive care unit stay (p = 0.087), and mortality (p > 0.99). CONCLUSIONS: Dexmedetomidine during CPB is an effective cardioprotective agent in TOF children having surgery. Postoperative mortality was comparable across groups.