Prognostic value of myocardial deformation parameters for outcome prediction in tetralogy of Fallot.

INTRODUCTION: The prognostic value of myocardial deformation parameters in adults with repaired tetralogy of Fallot (rTOF) has not been well-elucidated. We therefore aimed to explore myocardial deformation parameters for outcome prediction in adults with rTOF using cardiovascular magnetic resonance imaging (CMR). METHODS: Adults with rTOF and at least moderate pulmonary regurgitation (PR) were identified from an institutional prospective CMR registry. Left (LV) and right ventricular (RV) global strain were recorded in longitudinal (GLS), circumferential (GCS) and radial (GRS) directions. Major adverse cardiovascular events (MACE) were defined as a composite of mortality, resuscitated sudden death, sustained ventricular tachycardia (>30seconds) or heart failure (hospital admission >24hours). In patients with pulmonary valve replacement (PVR), pre-and post-PVR CMR studies were analysed to assess for predictors of complete RV reverse remodelling, which we defined as RV end-diastolic volume indexed (RVEDVi) <110ml/m2. Logistic regression models were used to estimate the odds ratio (OR) per unit change in absolute strain value associated with clinical outcomes and receiver operator characteristic (ROC) curves were constructed with area under the curve (AUC) for select CMR variables. RESULTS: We included 307 patients (age 35±13 years, 59% male). During 6.1 years (3.3-8.8) of follow-up, pulmonary valve replacement (PVR) was performed in 142 (46%) and MACE occurred in 31 (10%). On univariate analysis, baseline biventricular ejection fraction (EF), mass and all strain parameters were associated with MACE. After adjustment for LVEF, only LVGLS remained independently predictive of MACE (OR 0.822 [0.693-0.976] p=0.025). Receiver operator curves identified an absolute LVGLS value less than 15 and LVEF <51% as thresholds for MACE prediction (AUC 0.759 [0.655-0.840] and 0.720 [0.608-0.810]). After adjusting for baseline RVEDVi, RVGCS (OR 1.323 [1.094-1.600] p=0.004), LVGCS (OR 1.276 [1.029-1.582] p=0.027) and LVGRS (OR 1.101 [1.0210-1.200], p=0.028) were independent predictors of complete remodelling post-PVR remodelling. CONCLUSIONS: Biventricular strain parameters predict clinical outcomes and post-PVR remodelling in rTOF. Further study will be necessary to establish the role of myocardial deformation parameters in clinical practice.

Development and Validation of a Mortality Risk Score for Repaired Tetralogy of Fallot.

BACKGROUND: Robust risk assessment is crucial for the growing repaired tetralogy of Fallot population at risk of major adverse clinical outcomes; however, current tools are hindered by lack of validation. This study aims to develop and validate a risk prediction model for death in the repaired tetralogy of Fallot population. METHODS AND RESULTS: Patients with repaired tetralogy of Fallot enrolled in the INDICATOR (International Multicenter Tetralogy of Fallot Registry) cohort with clinical, arrhythmia, cardiac magnetic resonance, and outcome data were included. Patients from London, Amsterdam, and Boston sites were placed in the development cohort; patients from the Toronto site were used for external validation. Multivariable Cox regression was used to evaluate factors associated with time from cardiac magnetic resonance until the primary outcome: all-cause death. Of 1552 eligible patients (n=1221 in development, n=331 in validation; median age at cardiac magnetic resonance 23.4 [interquartile range, 15.6-35.6] years; median follow up 9.5 years), 102 (6.6%) experienced the primary outcome. The multivariable Cox model performed similarly during development (concordance index, 0.83 [95% CI, 0.78-0.88]) and external validation (concordance index, 0.80 [95% CI, 0.71-0.90]) and identified older age at cardiac magnetic resonance, obesity, type of tetralogy of Fallot repair, higher right ventricular end-systolic volume index, and lower biventricular global function index as independent predictors of death. A risk-scoring algorithm dividing patients into low-risk (score ≤4) versus high-risk (score >4) groups was validated to effectively discriminate risk of death (15-year survival of 95% versus 74%, respectively; P<0.001). CONCLUSIONS: This externally validated mortality risk prediction algorithm can help identify vulnerable patients with repaired tetralogy of Fallot who may benefit from targeted interventions.

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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Adherence to clinical practice guidelines for pulmonary valve intervention after tetralogy of Fallot repair: A nationwide cohort study.

Objectives: To determine guideline adherence pertaining to pulmonary valve replacement (PVR) referral after tetralogy of Fallot (TOF) repair. Methods: Children and adults with cardiovascular magnetic resonance imaging scans and at least moderate pulmonary regurgitation were prospectively enrolled in the Comprehensive Outcomes Registry Late After TOF Repair (CORRELATE). Individuals with previous PVR were excluded. Patients were classified according to presence (+) versus absence (-) of PVR and presence (+) versus absence (-) of contemporaneous guideline satisfaction. A validated score (specific activity scale [SAS]) classified adult symptom status. Results: In total, 498 participants (57% male, mean age 32 ± 14 years) were enrolled from 14 Canadian centers (2013-2020). Mean follow-up was 3.8 ± 1.8 years. Guideline criteria for PVR were satisfied for the majority (n = 422/498, 85%), although referral for PVR occurred only in a minority (n = 167/498, 34%). At PVR referral, most were asymptomatic (75% in SAS class 1). One participant (0.6%) received PVR without meeting criteria (PVR+/indication-). The remainder (n = 75/498, 15%) did not meet criteria for and did not receive PVR (PVR-/indication-). Abnormal cardiovascular imaging was the most commonly cited indication for PVR (n = 61/123, 50%). The SAS class and ratio of right to left end-diastolic volumes were independent predictors of PVR in a multivariable analysis (hazard ratio, 3.33; 95% confidence interval, 1.92-5.8, P < .0001; hazard ratio, 2.78; 95% confidence interval, 2.18-3.55, P < .0001). Conclusions: Although a majority of patients met guideline criteria for PVR, only a minority were referred for intervention. Abnormal cardiovascular imaging was the most common indication for referral. Further research will be necessary to establish the longer-term clinical impact of varying PVR referral strategies.

Incremental value of machine learning for risk prediction in tetralogy of Fallot.

OBJECTIVE: Machine learning (ML) can facilitate prediction of major adverse cardiovascular events (MACEs) in repaired tetralogy of Fallot (rTOF). We sought to determine the incremental value of ML above expert clinical judgement for risk prediction in rTOF. METHODS: Adult congenital heart disease (ACHD) clinicians (≥10 years of experience) participated (one cardiac surgeon and four cardiologists (two paediatric and two adult cardiology trained) with expertise in heart failure (HF), electrophysiology, imaging and intervention). Clinicians identified 10 high-yield variables for 5-year MACE prediction (defined as a composite of mortality, resuscitated sudden death, sustained ventricular tachycardia and HF). Risk for MACE (low, moderate or high) was assigned by clinicians blinded to outcome for adults with rTOF identified from an institutional database (n=25 patient reviews conducted by five independent observers). A validated ML model identified 10 variables for risk prediction in the same population. RESULTS: Prediction by ML was similar to the aggregate score of all experts (area under the curve (AUC) 0.85 (95% CI 0.58 to 0.96) vs 0.92 (0.72 to 0.98), p=0.315). Experts with ≥20 years of experience had superior discriminative capacity compared with <20 years (AUC 0.98 (95% CI 0.86 to 0.99) vs 0.80 (0.56 to 0.93), p=0.027). In those with <20 years of experience, ML provided incremental value such that the combined (clinical+ML) AUC approached ≥20 years (AUC 0.85 (95% CI 0.61 to 0.95), p=0.055). CONCLUSIONS: Robust prediction of 5-year MACE in rTOF was achieved using either ML or a multidisciplinary team of ACHD experts. Risk prediction of some clinicians was enhanced by incorporation of ML suggesting that there may be incremental value for ML in select circumstances.

Feasibility of MRI assessment of maternal-fetal oxygen transport and consumption relative to maternal position in healthy late gestational pregnancies.

Late gestational supine positioning reduces maternal cardiac output due to inferior vena caval (IVC) compression, despite increased collateral venous return. However, little is known about the impact of maternal position on oxygen (O2 ) delivery and consumption of the gravid uterus, fetus, placenta and lower limbs. We studied the effects of maternal positioning on these parameters in 20 healthy pregnant subjects at 36 ± 2 weeks using magnetic resonance imaging (MRI); a follow-up MRI was performed 6-months postpartum (n = 16/20). MRI techniques included phase-contrast and T1/T2 relaxometry for blood flow and oximetry imaging, respectively. O2 transport was measured in the following vessels (bilateral where appropriate): maternal abdominal descending aorta (DAoabdo ), IVC, ovarian, paraspinal veins (PSV), uterine artery (UtA) and external iliacs, and umbilical. Maternal cardiac output was measured by summing DAothoracic and superior vena cava flows. Supine mothers (n = 6) had lower cardiac output and O2 delivery in the DAoabdo , UtA and external iliac arteries, and higher PSV flow than those in either the left (n = 8) or right (n = 6) lateral positions during MRI. However, O2 consumption in the gravid uterus, fetus, placenta and lower limbs was unaffected by maternal positioning. The ratio of IVC/PSV flow decreased in supine mothers while ovarian venous flow and O2 saturation were unaltered, suggesting a major route of pelvic venous return unaffected by maternal position. Placental-fetal O2 transport and consumption were similar between left and right lateral maternal positions. In comparison to non-pregnant findings, DAoabdo and UtA O2 delivery and pelvic O2 consumption increased, while lower-limb consumption remained constant , despite reduced external iliac artery O2 delivery in late gestation. KEY POINTS: Though sleeping supine during the third trimester is associated with an increased risk of antepartum stillbirth, the underlying biological mechanisms are not fully understood. Maternal cardiac output and uteroplacental flow are reduced in supine mothers due to inferior vena caval compression from the weight of the gravid uterus. This MRI study provides a comprehensive circulatory assessment, demonstrating reduced maternal cardiac output and O2 delivery (uteroplacental, lower body) in supine compared to lateral positioning; however, O2 consumption (gravid uterus, fetus, placenta, lower limbs) was preserved. Unlike other mammalian species, the ovarian veins conduct substantial venous return from the human pregnant uterus that is unaffected by maternal positioning. Lumbar paraspinal venous flow increased in supine mothers. These observations may have important considerations during major pelvic surgery in pregnancy (i.e. placenta percreta). Future studies should address the importance of maternal positioning as a potential tool to deliver improved perinatal outcomes in pregnancies with compromised uteroplacental O2 delivery.

Mitral annular disjunction on cardiac MRI: Prevalence and association with disease severity in Loeys-Dietz syndrome.

BACKGROUND: The purpose of this study was to evaluate mitral annular disjunction (MAD) on cardiac magnetic resonance imaging (MRI) in Loeys-Dietz Syndrome (LDS) and to explore its association with adverse outcomes. METHODS: In this retrospective cohort study, adult patients with LDS who underwent cardiac MRI were evaluated for MAD, aortic dimensions, and ventricular volumetry. Aortic events were defined as aortic surgery and/or dissection and severe arrhythmic events as cardiac arrest or sustained ventricular tachycardia (VT). RESULTS: Among 46 LDS patients (52% female, 37.2 ± 14.3 years), 17 had MAD (37%). MAD and no MAD groups were similar in age, sex, aortic dimensions and left ventricular parameters. After a clinical follow-up of 4.3 years (IQR 1.5-8.4), 3 in MAD and 4 in no MAD groups required aortic valve sparing root replacement (VSRR) and 1 in MAD developed type A dissection. Over a similar imaging follow-up period [4.1 years (IQR 2.7-9.1) vs. 3.2 years (IQR 1.0-9.0), p = 0.65], compared to baseline, increase in native aortic root size was significant only in MAD (39.4 ± 4.6 mm vs. 38.1 ± 5.3 mm, p = 0.02, 19.3 ± 2.4 mm/m2 vs. 18.7 ± 2.4 mm/m2, p = 0.01) compared to those without MAD. Patients with MAD were younger at first aortic event compared to those without (26.7 ± 11.5 years vs. 45.0 ± 14.9 years, p = 0.03). MAD distance correlated with need for VSRR, r = 0.57, p = 0.02. Two patients in the MAD group developed sustained VT. No cardiac arrest or death was observed. CONCLUSION: MAD is highly prevalent in LDS, associated with progressive aortic dilatation, and aortic events at younger age. MAD may be a marker of disease severity necessitating close surveillance.

Long-Term Outcomes of Unrepaired Isolated Partial Anomalous Pulmonary Venous Connection With an Intact Atrial Septum.

The natural history of an unrepaired isolated partial anomalous pulmonary venous connection(s) (PAPVC) and the absence of other congenital anomalies remains unclear. This study aimed to expand the understanding of the clinical outcomes in this population. Isolated PAPVC with an intact atrial septum is a relatively uncommon condition. There is the perception that patients with isolated PAPVC are usually asymptomatic, that the lesion generally has a limited hemodynamic impact, and that surgical repair is rarely justified. For this retrospective study, we reviewed our institutional database to identify patients with either 1 or 2 anomalous pulmonary veins that drain a portion of but not the complete ipsilateral lung. Patients with previous surgical cardiac repair, coexistence of other congenital cardiac anomalies that would result in either pretricuspid or post-tricuspid loading of the right ventricle (RV), or scimitar syndrome were excluded. We reviewed their clinical course over the follow-up period. We identified 53 patients; 41 with a single and 12 with 2 anomalous PAPVC. A total of 30 patients (57%) were men, with a mean age at the latest clinic visit of 47 ± 19 years (18 to 84 years). Turner syndrome (6 of 53, 11.3%), bicuspid aortic valve (6 of 53, 11.3%), and coarctation of the aorta (5 of 53, 9.4%) were commonly associated anomalies. A single anomalous left upper lobe vein was the most commonly identified variation. More than half of the patients were asymptomatic. Cardiopulmonary exercise test demonstrated a maximal oxygen consumption of 73 ± 20% expected (36 to 120). Transthoracic echocardiography demonstrated a mean RV basal diameter of 4.4 ± 0.8 cm, RV systolic pressure of 38 ± 13 (16 to 84) mm Hg. A total of 8 patients (14.8%) had ≥moderate tricuspid regurgitation. Cardiac magnetic resonance in 42 patients demonstrated a mean RV end-diastolic volume index of 122 ±3 0 ml/m2 (66 to 188 ml/m2), of which in 8 (14.8%), it was >150 ml/m2. Magnetic resonance imaging-based Qp:Qs was 1.6 ± 0.3. A total of 5 patients (9.3%) had established pulmonary hypertension (mean pulmonary artery pressure ≥25 mm Hg). In conclusion, isolated single or dual anomalous pulmonary venous connection is not necessarily a benign congenital anomaly because a proportion of patients develop pulmonary hypertension and/or RV dilation. Regular follow-up and on-going patient surveillance with cardiac imaging is advised.

Machine Learning for Prediction of Adverse Cardiovascular Events in Adults With Repaired Tetralogy of Fallot Using Clinical and Cardiovascular Magnetic Resonance Imaging Variables.

BACKGROUND: Existing models for prediction of major adverse cardiovascular events (MACE) after repair of tetralogy of Fallot have been limited by modest predictive capacity and limited applicability to routine clinical practice. We hypothesized that an artificial intelligence model using an array of parameters would enhance 5-year MACE prediction in adults with repaired tetralogy of Fallot. METHODS: A machine learning algorithm was applied to 2 nonoverlapping, institutional databases of adults with repaired tetralogy of Fallot: (1) for model development, a prospectively constructed clinical and cardiovascular magnetic resonance registry; (2) for model validation, a retrospective database comprised of variables extracted from the electronic health record. The MACE composite outcome included mortality, resuscitated sudden death, sustained ventricular tachycardia and heart failure. Analysis was restricted to individuals with MACE or followed ≥5 years. A random forest model was trained using machine learning (n=57 variables). Repeated random sub-sampling validation was sequentially applied to the development dataset followed by application to the validation dataset. RESULTS: We identified 804 individuals (n=312 for development and n=492 for validation). Model prediction (area under the curve [95% CI]) for MACE in the validation dataset was strong (0.82 [0.74-0.89]) with superior performance to a conventional Cox multivariable model (0.63 [0.51-0.75]; P=0.003). Model performance did not change significantly with input restricted to the 10 strongest features (decreasing order of strength: right ventricular end-systolic volume indexed, right ventricular ejection fraction, age at cardiovascular magnetic resonance imaging, age at repair, absolute ventilatory anaerobic threshold, right ventricular end-diastolic volume indexed, ventilatory anaerobic threshold % predicted, peak aerobic capacity, left ventricular ejection fraction, and pulmonary regurgitation fraction; 0.81 [0.72-0.89]; P=0.232). Removing exercise parameters resulted in inferior model performance (0.75 [0.65-0.84]; P=0.002). CONCLUSIONS: In this single-center study, a machine learning-based prediction model comprised of readily available clinical and cardiovascular magnetic resonance imaging variables performed well in an independent validation cohort. Further study will determine the value of this model for risk stratification in adults with repared tetralogy of Fallot.

Electromechanical Dyssynchrony Is Associated With Right Ventricular Remodeling and Dysfunction Independently of Pulmonary Regurgitation Late After Tetralogy of Fallot Repair.

BACKGROUND: The aim of this study was to investigate the relationship among right ventricular (RV) dilatation, dysfunction, and electromechanical dyssynchrony (EMD) in patients with repaired tetralogy of Fallot (rTOF). METHODS: Data from a prospective rTOF registry of subjects with moderate or greater pulmonary regurgitation (PR) and contemporary imaging were analyzed. Electrocardiograms and echocardiograms were analyzed for EMD (prolonged QRS duration [QRSd], echocardiographic septal flash, and mechanical delay) and mechanical dispersion. The relationship among these, RV measurements on cardiac magnetic resonance, exercise capacity, and incident arrhythmia or death was analyzed with adjustment for PR. RESULTS: In total, 271 patients with rTOF (42% women; median age, 32 years; interquartile range [IQR], 23-34 years) were included. Patients had moderate to severe PR (median PR fraction, 38%; IQR, 30%-47%), moderate to severe RV enlargement (median RV end-diastolic volume index, 161 mL/m2; IQR, 138-186 mL/m2) and mild RV systolic dysfunction (median RV ejection fraction [RVEF], 44%; IQR, 38%-48%). Eleven patients (4%) experienced ventricular arrhythmia or death. Presence of EMD was associated with larger RV size (RV end-diastolic volume index and RV end-systolic volume index, P = .006 and P < .001, respectively) and lower RVEF (P < .001). A sharp inflection in the relation among QRSd, RV size, and RVEF was observed when QRSd exceeded 150 msec (3.1% decrease in RVEF for every 20-msec increase in QRSd between 160 and 200 msec). Similar inflection points were observed for the mechanical delay between the RV basal-lateral and midseptal segments. The mechanical delay was higher in patients with vs without incident atrial arrhythmia (371 vs 276 msec, P = .014). CONCLUSIONS: In adults with rTOF, EMD is independently associated with larger RV size, lower RVEF, and incident atrial arrhythmias.

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

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

Patient-Reported Outcomes After Tetralogy of Fallot Repair.

BACKGROUND: Comprehensive assessment of tetralogy of Fallot (TOF) outcomes extends beyond morbidity and mortality to incorporate patient-reported outcomes (PROs), including quality of life (QOL) and health status (HS). OBJECTIVES: This study explored PROs in adolescents and adults with TOF and delineated variables associated with PROs. METHODS: This was a cross-sectional observational study within a larger prospective registry of adolescents and adults with repaired TOF and moderate or greater pulmonary regurgitation from North America, Europe, and Asia. Participants completed PROs, including a QOL linear analogue scale (QOL-LAS) and an HS visual analogue scale (HS-VAS). Scores were classified according to age cohorts: <18, 18 to 25, 26 to 40, and >40 years. RESULTS: The study included 607 patients (46.3% female; median age 28.5 years). Median QOL-LAS scores (0-100) were similar across age cohorts (85, 80, 80, 80; P = 0.056). Median HS-VAS scores (0-100) were lowest for the oldest cohort (77) compared with the 3 younger cohorts (85, 80, 80) (P = 0.004). With advancing age, there were increased reports of poor mobility (P < 0.001) and pain or discomfort (P = 0.004); problems in these dimensions were reported by 19.1% and 37.2% of patients aged >40 years, respectively. Of factors associated with superior PROs on multivariable regression modeling (ie, being White, being nonsyndromic, having employment, and having better left ventricular function; P < 0.05), asymptomatic status (functional class I) was the variable associated with the greatest number of QOL and HS measures (P < 0.001). CONCLUSIONS: Strategies to improve TOF outcomes should consider PROs alongside conventional clinical variables. Factors associated with poorer PROs represent opportunities to intervene to improve the lives of patients with TOF.

Myocarditis Following COVID-19 Vaccination.

Myocarditis is an established but rare adverse event following administration of messenger RNA-based coronavirus disease 2019 (COVID-19) vaccines and is most common in male adolescents and young adults. Symptoms typically develop within a few days of vaccine administration. Most patients have mild abnormalities on cardiac imaging with rapid clinical improvement with standard treatment. However, longer term follow-up is needed to determine whether imaging abnormalities persist, to evaluate for adverse outcomes, and to understand the risk associated with subsequent vaccination. The purpose of the review is to evaluate the current literature related to myocarditis following COVID-19 vaccination, including the incidence, risk factors, clinical course, imaging findings, and proposed pathophysiologic mechanisms.

Myocardial Inflammation on FDG PET/MRI and Clinical Outcomes in Symptomatic and Asymptomatic Participants after COVID-19 Vaccination.

Purpose: To evaluate potential cardiac sequelae of COVID-19 vaccination at 2-month follow-up and relate cardiac symptoms to myocardial tissue changes on fluorodeoxyglucose (FDG) PET/MRI, blood biomarkers, health-related quality of life, and adverse outcomes. Materials and Methods: In this prospective study (ClinicalTrials.gov: NCT04967807), a convenience sample of individuals aged ≥17 years were enrolled after COVID-19 vaccination and were categorized as symptomatic myocarditis (new cardiac symptoms within 14 days of vaccination and met diagnostic criteria for acute myocarditis), symptomatic no myocarditis (new cardiac symptoms but did not meet criteria for myocarditis), and asymptomatic (no new cardiac symptoms). Standardized evaluation was performed 2 months after vaccination, including cardiac fluorine 18 FDG PET/MRI, blood biomarkers, and health-related quality of life. Statistical analysis included Kruskal-Wallis and Fisher exact tests. Results: Fifty-four participants were evaluated a median of 72 days (IQR: 42, 91) after COVID-19 vaccination, 17 symptomatic with myocarditis (36±[SD]15 years, 13 males), 17 symptomatic without myocarditis (42±12 years, 7 males), and 20 asymptomatic (45±14 years, 9 males). No participants in the symptomatic without myocarditis or asymptomatic groups had focal FDG-uptake, myocardial edema or impaired ventricular function. Two participants with symptomatic myocarditis had focal FDG-uptake, and three had high T2 on MRI. Health-related quality of life was lower in the symptomatic myocarditis group than the asymptomatic group. There were no adverse cardiac events beyond myocarditis in any participant. Conclusions: At two-month follow-up, FDG PET/MRI showed evidence of myocardial inflammation in 2/17 participants diagnosed with acute myocarditis early after COVID-19 vaccination, but not in symptomatic and asymptomatic participants without acute myocarditis.Keywords: Myocarditis, Vaccination, COVID-19, PET/MRI, Cardiac MRI, FDG-PET.

Cardiac Magnetic Resonance Imaging T1 and T2 Mapping in Systemic Lupus Erythematosus in Relation to Antimalarial Treatment.

PURPOSE: Patients with systemic lupus erythematosus (SLE) are at risk of cardiac disease including antimalarial-induced cardiomyopathy (AMIC). The purpose of this study is to evaluate cardiac magnetic resonance imaging parametric mapping findings in SLE patients with AMIC and investigate the relationship of T1/T2 mapping to antimalarial (AM) treatment duration. MATERIALS AND METHODS: All patients with SLE who had undergone cardiac magnetic resonance imaging with T1/T2 mapping for evaluation of suspected cardiac disease between 2018 and 2021 were evaluated and compared with healthy controls. To facilitate comparison between scanners, T1/T2 values were converted to a z -score using scanner-specific local reference values. Patients were classified into 3 groups: AMIC, myocarditis, and other (no AMIC or myocarditis). RESULTS: Forty-five SLE patients (47±17 y, 80% female; 8 [18%] with AMIC and 7 [16%] with myocarditis) and 30 healthy controls (39±15 y, 60% female) were included. Patients with AMIC had higher T1 and T2 compared with controls ( z -score 1.1±1.3 vs. 0±0.6, P =0.01 and 1.7±1.1 vs. 0±1.0, P <0.01, respectively) and lower values compared with those with myocarditis (3.7±1.6, P <0.01 and 4.0±2.0, P <0.01, respectively). T1 correlated negatively with AM treatment duration in patients without AMIC or myocarditis ( r =-0.36, P =0.048) and positively in patients with AMIC ( r =0.92, P =0.001). AM treatment duration did not correlate significantly with T1 in patients with myocarditis or with T2 in any group. CONCLUSIONS: The relationship between T1 and AM treatment duration differed between groups. Native T1 decreases with longer treatment in patients without AMIC or myocarditis, possibility due to glycosphingolipid accumulation. In patients with AMIC, increasing T1 with longer treatment could reflect fibrosis.

Association of Pectus Excavatum With Ventricular Remodelling and Mitral Valve Abnormalities in Marfan Syndrome.

Background: Marfan syndrome (MFS) is an inherited connective tissue disorder. Pectus excavatum (PEX) is common in MFS. The purpose was to evaluate the association of PEX with cardiovascular manifestations of MFS, biventricular size and function. Methods: MFS adults undergoing cardiac MRI were retrospectively evaluated. Exclusion criteria were incomplete cardiac MRI, significant artifacts, co-existent ischaemic or congenital heart disease. Haller Index (HI) ≥3.25 classified patients as PEX positive (PEX+) and PEX negative (PEX-). Cardiac MRI analysis included assessment of mitral valve prolapse (MVP), mitral annular disjunction (MAD), biventricular volumetry and aortic dimensions. Results: 212 MFS patients were included, 76 PEX+ and 136 PEX- (HI 8.3 ± 15.2 vs 2.3 ± 0.5, P < .001). PEX+ were younger (33.4 ± 12.0 vs 38.1 ± 14.3 years, P = .02) and similar in sex distribution (55% vs 63% male, P = .26) compared to PEX-. MVP and MAD were more frequent in PEX+ vs PEX- (43/76 [57%] vs 37/136 [27%], P < .001; 44/76 [58%] vs 50/136[37%], P = .003, respectively). PEX+ had higher right ventricular end-diastolic and end-systolic volumes (RVEDVi 92 ± 17mL/m2 vs 84 ± 22mL/m2, P = .04; RVESVi 44 ± 10 mL/m2 vs 39 ± 14 mL/m2, P = .02), lower RV ejection fraction (RVEF 52 ± 5% vs 55 ± 6%, P = .01) compared to PEX-. Left ventricular (LV) volumes, LVEF and aortic dimensions were similar. Conclusion: MFS adults with PEX have higher frequency of cardiac manifestations including MV abnormalities, increased RV volumes and lower RVEF compared to those without PEX. Awareness of this association is important for all radiologists who interpret aortic CT or MRI, where HI can be easily measured. PEX in MFS may suggest more severe disease expression necessitating careful screening for MV abnormalities and outcomes surveillance.