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.

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.

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.

Prognostic value of cardiovascular magnetic resonance left ventricular volumetry and geometry in patients receiving an implantable cardioverter defibrillator.

BACKGROUND: Current indications for implantable cardioverter defibrillator (ICD) implantation for sudden cardiac death prevention rely primarily on left ventricular (LV) ejection fraction (LVEF). Currently, two different contouring methods by cardiovascular magnetic resonance (CMR) are used for LVEF calculation. We evaluated the comparative prognostic value of these two methods in the ICD population, and if measures of LV geometry added predictive value. METHODS: In this retrospective, 2-center observational cohort study, patients underwent CMR prior to ICD implantation for primary or secondary prevention from January 2005 to December 2018. Two readers, blinded to all clinical and outcome data assessed CMR studies by: (a) including the LV trabeculae and papillary muscles (TPM) (trabeculated endocardial contours), and (b) excluding LV TPM (rounded endocardial contours) from the total LV mass for calculation of LVEF, LV volumes and mass. LV sphericity and sphere-volume indices were also calculated. The primary outcome was a composite of appropriate ICD shocks or death. RESULTS: Of the 372 consecutive eligible patients, 129 patients (34.7%) had appropriate ICD shock, and 65 (17.5%) died over a median duration follow-up of 61 months (IQR 38-103). LVEF was higher when including TPM versus excluding TPM (36% vs. 31%, p < 0.001). The rate of appropriate ICD shock or all-cause death was higher among patients with lower LVEF both including and excluding TPM (p for trend = 0.019 and 0.004, respectively). In multivariable models adjusting for age, primary prevention, ischemic heart disease and late gadolinium enhancement, both LVEF (HR per 10% including TPM 0.814 [95%CI 0.688-0.962] p = 0.016, vs. HR per 10% excluding TPM 0.780 [95%CI 0.639-0.951] p = 0.014) and LV mass index (HR per 10 g/m2 including TPM 1.099 [95%CI 1.027-1.175] p = 0.006; HR per 10 g/m2 excluding TPM 1.126 [95%CI 1.032-1.228] p = 0.008) had independent prognostic value. Higher LV end-systolic volumes and LV sphericity were significantly associated with increased mortality but showed no added prognostic value. CONCLUSION: Both CMR post-processing methods showed similar prognostic value and can be used for LVEF assessment. LVEF and indexed LV mass are independent predictors for appropriate ICD shocks and all-cause mortality in the ICD population.

Increased Spread of Native T1 Values Assessed With MRI as a Marker of Cardiac Involvement in Fabry Disease.

OBJECTIVE. Cardiac involvement is the leading cause of mortality in Fabry disease. Noninvasive markers of cardiac involvement are needed to identify patients at high risk. The purpose of this study was to evaluate the diagnostic potential of segmental native T1 spread as an imaging biomarker in Fabry disease. SUBJECTS AND METHODS. In this prospective study, 43 patients with confirmed Fabry disease (mean ± SD age, 46±14 years; 70% women) and 17 healthy control subjects (mean ± SD age, 44 ±13 years; 53% women) underwent 3-T cardiac MRI including modified Look-Locker inversion recovery T1 mapping. Segmental native T1 spread was calculated as the difference between maximum and minimum segmental native T1 values, expressed as an absolute value and as a relative percentage of global native T1. RESULTS. Absolute and relative segmental native T1 spreads were significantly higher in patients with Fabry disease than in healthy control subjects (absolute median, 115 vs 98 ms [p = 0.004]; relative median, 9.9% vs 8.0% [p < 0.001]) and correlated positively with quantitative late gadolinium enhancement (absolute, r = 0.434, p < 0.001; relative, r = 0.436, p < 0.001), indexed left ventricular mass (absolute, r = 0.316, p = 0.01; relative, r = 0.347, p = 0.007), and global longitudinal strain (absolute, r = 0.289, p = 0.03; relative, r = 0.277, p = 0.03). Relative segmental native T1 spread differentiated patients with Fabry disease from healthy control subjects (odds ratio, 1.44 [95% CI, 1.10-1.89]; p = 0.009). Interob-server agreement was excellent for both absolute (intraclass correlation coefficient, 0.932) and relative (intraclass correlation coefficient, 0.926) segmental native T1 spread. CONCLUSION. Increased native T1 spread is a reproducible imaging biomarker of cardiac involvement in Fabry disease and may be particularly useful in the evaluation of patients who cannot undergo late gadolinium enhancement imaging.

Left Ventricular Hypertrophy and Late Gadolinium Enhancement at Cardiac MRI Are Associated with Adverse Cardiac Events in Fabry Disease.

Background Cardiac involvement is the leading cause of mortality in patients with Fabry disease. Identification of imaging findings that predict adverse cardiac events is needed to enable identification of high-risk patients. Purpose To establish the prognostic value of cardiac MRI findings in men and women with Fabry disease. Materials and Methods Consecutive women and men with gene-positive Fabry disease who had undergone cardiac MRI at a single large tertiary referral hospital between March 2008 and January 2019 were included in this retrospective cohort study. Evaluators of cardiac MRI studies were blinded to all clinical information. Adverse cardiac events were assessed as a composite end point, defined as ventricular tachycardia, bradycardia requiring device implantation, severe heart failure, and cardiac death. Statistical analysis included Cox proportional hazard models adjusted for age and Mainz Severity Score Index (a measure of the severity of Fabry disease). Results Ninety patients (mean age, 44 years ± 15 [standard deviation]; 59 women) were evaluated. After a median follow-up period of 3.6 years, the composite end point was reached in 21 patients (incidence rate, 7.6% per year). Left ventricular hypertrophy (LVH) and late gadolinium enhancement (LGE) were independent predictors of the composite end point in adjusted analysis (LVH hazard ratio [HR], 3.0; 95% confidence interval [CI]: 1.1, 8.1; P = .03; and LGE HR, 7.2; 95% CI: 1.5, 34; P = .01). Patients with extensive LGE (≥15% of left ventricular mass) were at highest risk (HR, 12; 95% CI: 2.0, 67; P = .006). Sex did not modify the relationship between the composite end point and any of the cardiac MRI parameters, including LVH (P = .15 for interaction term) and LGE (P = .38 for interaction term). Conclusion Cardiac MRI findings of left ventricular hypertrophy and late gadolinium enhancement can be used to identify patients with Fabry disease who are at high risk of adverse cardiac events. © RSNA, 2019 See also the editorial by Zimmerman in this issue.

Progressive right ventricular outflow tract fibrosis after repair of tetralogy of Fallot.

OBJECTIVES: The objective of this study was to determine the evolution of fibrosis over time and its association with clinical status. METHODS: Children with repaired tetralogy of Fallot who had undergone at least two cardiac magnetic resonance examinations including T1 mapping at least 1 year apart were included. RESULTS: Thirty-seven patients (12.7 ± 2.6 years, 61% male) were included. Right ventricular free wall T1 increased (913 ± 208 versus 1023 ± 220 ms; p = 0.02). Baseline cardiac magnetic resonance parameters did not predict a change in imaging markers or exercise tolerance. The right ventricular free wall per cent change correlated with left ventricular T1% change (r = 0.51, p = 0.001) and right ventricular mass Z-score change (r = 0.51, p = 0.001). T1 in patients with late gadolinium enhancement did not differ from the rest. CONCLUSION: Increasing right ventricular free wall T1 indicates possible progressive fibrotic remodelling in the right ventricular outflow tract in this pilot study in children and adolescents with repaired tetralogy of Fallot. The value of T1 mapping both at baseline and during serial assessments will need to be investigated in larger cohorts with longer follow-up.

Loss of base-to-apex circumferential strain gradient assessed by cardiovascular magnetic resonance in Fabry disease: relationship to T1 mapping, late gadolinium enhancement and hypertrophy.

BACKGROUND: Cardiac involvement is common and is the leading cause of mortality in Fabry disease (FD). We explored the association between cardiovascular magnetic resonance (CMR) myocardial strain, T1 mapping, late gadolinium enhancement (LGE) and left ventricular hypertrophy (LVH) in patients with FD. METHODS: In this prospective study, 38 FD patients (45.0 ± 14.5 years, 37% male) and 8 healthy controls (40.1 ± 13.7 years, 63% male) underwent 3 T CMR including cine balanced steady-state free precession (bSSFP), LGE and modified Look-Locker Inversion recovery (MOLLI) T1 mapping. Global longitudinal (GLS) and circumferential (GCS) strain and base-to-apex longitudinal strain (LS) and circumferential strain (CS) gradients were derived from cine bSSFP images using feature tracking analysis. RESULTS: Among FD patients, 8 had LVH (FD LVH+, 21%) and 17 had LGE (FD LGE+, 45%). Nineteen FD patients (50%) had neither LVH nor LGE (FD LVH- LGE-). None of the healthy controls had LVH or LGE. FD patients and healthy controls did not differ significantly with respect to GLS (- 15.3 ± 3.5% vs. - 16.3 ± 1.5%, p = 0.45), GCS (- 19.4 ± 3.0% vs. -19.5 ± 2.9%, p = 0.84) or base-to-apex LS gradient (7.5 ± 3.8% vs. 9.3 ± 3.5%, p = 0.24). FD patients had significantly lower base-to-apex CS gradient (2.1 ± 3.7% vs. 6.5 ± 2.2%, p = 0.002) and native T1 (1170.2 ± 37.5 ms vs. 1239.0 ± 18.0 ms, p < 0.001). Base-to-apex CS gradient differentiated FD LVH- LGE- patients from healthy controls (OR 0.42, 95% CI: 0.20 to 0.86, p = 0.019), even after controlling for native T1 (OR 0.24, 95% CI: 0.06 to 0.99, p = 0.049). In a nested logistic regression model with native T1, model fit was significantly improved by the addition of base-to-apex CS gradient (χ2(df = 1) = 11.04, p < 0.001). Intra- and inter-observer agreement were moderate to good for myocardial strain parameters: GLS (ICC 0.849 and 0.774, respectively), GCS (ICC 0.831 and 0.833, respectively), and base-to-apex CS gradient (ICC 0.737 and 0.613, respectively). CONCLUSIONS: CMR reproducibly identifies myocardial strain abnormalities in FD. Loss of base-to-apex CS gradient may be an early marker of cardiac involvement in FD, with independent and incremental value beyond native T1.

Use of Myocardial T1 Mapping at 3.0 T to Differentiate Anderson-Fabry Disease from Hypertrophic Cardiomyopathy.

Purpose To compare left ventricular (LV) and right ventricular (RV) 3.0-T cardiac magnetic resonance (MR) imaging T1 values in Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM) and evaluate the diagnostic value of native T1 values beyond age, sex, and conventional imaging features. Materials and Methods For this prospective study, 30 patients with gene-positive AFD (37% male; mean age ± standard deviation, 45.0 years ± 14.1) and 30 patients with HCM (57% male; mean age, 49.3 years ± 13.5) were prospectively recruited between June 2016 and September 2017 to undergo cardiac MR imaging T1 mapping with a modified Look-Locker inversion recovery (MOLLI) acquisition scheme at 3.0 T (repetition time msec/echo time msec, 280/1.12; section thickness, 8 mm). LV and RV T1 values were evaluated. Statistical analysis included independent samples t test, receiver operating characteristic curve analysis, multivariable logistic regression, and likelihood ratio test. Results Septal LV, global LV, and RV native T1 values were significantly lower in AFD compared with those in HCM (1161 msec ± 47 vs 1296 msec ± 55, respectively [P < .001]; 1192 msec ± 52 vs 1268 msec ± 55 [P < .001]; and 1221 msec ± 54 vs 1271 msec ± 37 [P = .001], respectively). A septal LV native T1 cutoff point of 1220 msec or lower distinguished AFD from HCM with sensitivity of 97%, specificity of 93%, and accuracy of 95%. Septal LV native T1 values differentiated AFD from HCM after adjustment for age, sex, and conventional imaging features (odds ratio, 0.94; 95% confidence interval: 0.91, 0.98; P = < .001). In a nested logistic regression model with age, sex, and conventional imaging features, model fit was significantly improved by the addition of septal LV native T1 values (χ2 [df = 1] = 33.4; P < .001). Conclusion Cardiac MR imaging native T1 values at 3.0 T are significantly lower in patients with AFD compared with those with HCM and provide independent and incremental diagnostic value beyond age, sex, and conventional imaging features. © RSNA, 2018.

Association between conversion to in-center nocturnal hemodialysis and right ventricular remodeling.

Background: In-center nocturnal hemodialysis (INHD) is associated with favorable left ventricular (LV) remodeling. Although right ventricular (RV) structure and function carry prognostic significance, the impact of dialysis intensification on RV is unknown. Our objectives were to evaluate changes in RV mass index (MI), end-diastolic volume index (EDVI), end-systolic volume index (ESVI) and ejection fraction (EF) after conversion to INHD and their relationship with LV remodeling. Methods: Of 67 conventional hemodialysis (CHD, 4 h/session, three times/week) patients, 30 continued on CHD and 37 converted to INHD (7-8 h/session, three times/week). Cardiac magnetic resonance imaging was performed at baseline and 1 year using a standardized protocol; an experienced and blinded reader performed RV measurements. Results: At 1 year there were significant reductions in RVMI {-2.1 g/m2 [95% confidence interval (CI) -3.8 to - 0.4], P = 0.017}, RVEDVI [-9.5 mL/m2 (95% CI - 16.3 to - 2.6), P = 0.008] and RVESVI [-6.2 mL/m2 (95% CI - 10.9 to - 1.6), P = 0.011] in the INHD group; no significant changes were observed in the CHD group. Between-group comparisons showed significantly greater reduction of RVESVI [-7.9 mL/m2 (95% CI - 14.9 to - 0.9), P = 0.03] in the INHD group, a nonsignificant trend toward greater reduction in RVEDVI and no significant difference in RVMI and RVEF changes. There was significant correlation between LV and RV in terms of changes in mass index (MI) (r = 0.46), EDVI (r = 0.73), ESVI (r = 0.7) and EF (r = 0.38) over 1 year (all P < 0.01). Conclusions: Conversion to INHD was associated with a significant reduction of RVESVI. Temporal changes in RV mass, volume and function paralleled those of LV. Our findings support the need for larger, longer-term studies to confirm favorable RV remodeling and determine its impact on clinical outcomes.

Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study.

BACKGROUND: There are limited data on the effects of trastuzumab on the right ventricle (RV). Therefore, we sought to evaluate the temporal changes in right ventricular (RV) structure and function as measured by cardiovascular magnetic resonance (CMR), and their relationship with left ventricular (LV) structure and function in breast cancer patients treated with trastuzumab. METHODS: Prospective, longitudinal, observational study involving 41 women with HER2+ breast cancer who underwent serial CMR at baseline, 6, 12, and 18 months after initiation of trastuzumab. A single blinded observer measured RV parameters on de-identified CMRs in a random order. Linear mixed models were used to investigate temporal changes in RV parameters. RESULTS: Of the 41 women (age 52 ± 11 years), only one patient experienced trastuzumab-induced cardiotoxicity. Compared to baseline, there were small but significant increases in the RV end-diastolic volume at 6 months (p = 0.002) and RV end-systolic volume at 6 and 12 months (p < 0.001 for both), but not at 18 months (p = 0.82 and 0.13 respectively). RV ejection fraction (RVEF), when compared to baseline (58.3%, 95% CI 57.1-59.5%), showed corresponding decreases at 6 months (53.9%, 95% CI 52.5-55.4%, p < 0.001) and 12 months (55%, 95% CI 53.8-56.2%, p < 0.001) that recovered at 18 months (56.6%, 95% CI 55.1-58.0%, p = 0.08). Although the temporal pattern of changes in LVEF and RVEF were similar, there was no significant correlation between RVEF and LVEF at baseline (r = 0.29, p = 0.07) or between their changes at 6 months (r = 0.24, p = 0.17). CONCLUSION: In patients receiving trastuzumab without overt cardiotoxicity, there is a subtle but significant deleterious effect on RV structure and function that recover at 18 months, which can be detected by CMR. Furthermore, monitoring of LVEF alone may not be sufficient in detecting early RV injury. These novel findings provide further support for CMR in monitoring early cardiotoxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01022086 . Date of registration: November 27, 2009.

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.

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.

Clinical Significance of Papillary Muscles on Left Ventricular Mass Quantification Using Cardiac Magnetic Resonance Imaging: Reproducibility and Prognostic Value in Fabry Disease.

PURPOSE: Accurate and reproducible assessment of left ventricular mass (LVM) is important in Fabry disease. However, it is unclear whether papillary muscles should be included in LVM assessed by cardiac magnetic resonance imaging (MRI). The purpose of this study was to evaluate the reproducibility and predictive value of LVM in patients with Fabry disease using different analysis approaches. MATERIALS AND METHODS: A total of 92 patients (44±15 y, 61 women) with confirmed Fabry disease who had undergone cardiac MRI at a single tertiary referral hospital were included in this retrospective study. LVM was assessed at end-diastole using 2 analysis approaches, including and excluding papillary muscles. Adverse cardiac events were assessed as a composite end point, defined as ventricular tachycardia, bradycardia requiring device implantation, severe heart failure, and cardiac death. Statistical analysis included Cox proportional hazard models, Akaike information criterion, intraclass correlation coefficients, and Bland-Altman analysis. RESULTS: Left ventricular end-diastolic volume, end-systolic volume, ejection fraction, and LVM all differed significantly between analysis approaches. LVM was significantly higher when papillary muscles were included versus excluded (157±71 vs. 141±62 g, P<0.001). Mean papillary mass was 16±11 g, accounting for 10%±3% of total LVM. LVM with pap illary muscles excluded had slightly better predictive value for the composite end point compared with LVM with papillary muscles included based on the model goodness-of-fit (Akaike information criterion 140 vs. 142). Interobserver agreement was slightly better for LVM with papillary muscles excluded compared with included (intraclass correlation coefficient 0.993 [95% confidence interval: 0.985, 0.996] vs. 0.989 [95% confidence interval: 0.975, 0.995]) with less bias and narrower limits of agreement. CONCLUSIONS: Inclusion or exclusion of papillary muscles has a significant effect on LVM quantified by cardiac MRI, and therefore, a standardized analysis approach should be used for follow-up. Exclusion of papillary muscles from LVM is a reasonable approach in patients with Fabry disease given slightly better predictive value and reproducibility.

Cardiac MRI assessment of the right ventricle pre-and post-kidney transplant.

Worsening renal function in chronic kidney disease correlates with worsening right ventricular (RV) systolic function. We evaluated the association between kidney transplantation (KT) and RV structure and systolic function, and the relationships between RV and left ventricular (LV) changes, blood pressure, and specific cardiac biomarkers, in patients with end-stage kidney disease using cardiac magnetic resonance imaging (CMR). In this prospective, multi-centre, cohort study, 39 adult patients on dialysis receiving KT and 42 patients eligible for, but not yet receiving KT, were recruited. CMR was performed at baseline, and repeated at 12 months. Among 81 patients (mean age 51 years, 30% female), RV end-diastolic volume index (RVEDVi), end-systolic volume index (RVESVi), mass index (RVMi), and ejection fraction (RVEF) did not change significantly within either the dialysis or KT group over 12 months (all p ≥ 0.10). There were no significant differences in the 12-month changes of these parameters between the dialysis and KT groups (all p ≥ 0.10). RVMI demonstrated positive correlations with NT-proBNP and systolic blood pressure, but not GDF-15, at baseline and at 12 months. Changes in RVEDVi, RVESVi, and RVEF were positively correlated with changes in LVEDVi, LVESVi, and LVEF, respectively over 12 months (Spearman r = 0.72, 0.52, and 0.41; all p < 0.001), but not mass index (Spearman r = 0.20, p = 0.078). In conclusion, there were no significant changes in RV mass, volumes, or systolic function 12 months after KT, as compared with continuation of dialysis. The associations between RV and LV remodeling may suggest similar underlying pathophysiologic mechanisms.

Diagnostic Performance of Abnormal Nulling on Cardiac Magnetic Resonance Imaging Look Locker Inversion Time Sequence in Differentiating Cardiac Amyloidosis Types.

PURPOSE: To evaluate the diagnostic utility of the Look Locker inversion time (TI) sequence on cardiac magnetic resonance imaging in patients with suspected cardiac amyloidosis and to evaluate whether there are differences in the nulling pattern between amyloid types. MATERIALS AND METHODS: A total of 144 patients with suspected cardiac amyloidosis who had undergone cardiac magnetic resonance imaging were included in this retrospective study. Sixty-four had cardiac amyloidosis (62.1±9.2 y, 70.3% male, 68.8% had light chain amyloid [AL], 18.8% had familial transthyretin amyloid caused by mutant genes [ATTRm], and 12.5% had wild-type transthyretin amyloid [ATTRwt]) and 80 did not have cardiac amyloidosis (61.3±13.3 y, 58.8% male). Time to myocardial and blood pool nulling on the Look Locker TI sequence was classified as normal if blood pool nulled before myocardium or abnormal if blood pool nulling was coincident with or after myocardial nulling. RESULTS: The nulling pattern was abnormal in 26 patients with cardiac amyloidosis compared with none of the patients without cardiac amyloidosis (40.6% vs. 0.0%, P<0.0001). Abnormal nulling had 40.6% sensitivity and 100% specificity for cardiac amyloidosis (area under the receiver operating characteristic curve: 0.703, 95% confidence interval: 0.642-0.764). All patients with cardiac amyloidosis with an abnormal nulling pattern demonstrated late gadolinium enhancement. Among patients with cardiac amyloidosis, there was no significant difference in abnormal nulling between AL, ATTRm, and ATTRwt amyloid types (31.8%, 58.3%, 62.5%, respectively, P=0.10). CONCLUSIONS: An abnormal nulling pattern on the Look Locker TI sequence is highly specific for cardiac amyloidosis when present. However, abnormal nulling is a late finding with low sensitivity and does not differentiate between amyloid types.

Left Ventricular Mass and Wall Thickness Measurements Using Echocardiography and Cardiac MRI in Patients with Fabry Disease: Clinical Significance of Discrepant Findings.

PURPOSE: To compare transthoracic echocardiography (TTE) and cardiac MRI measurements of left ventricular mass (LVM) and maximum wall thickness (MWT) in patients with Fabry disease and evaluate the clinical significance of discrepancies between modalities. MATERIALS AND METHODS: Seventy-eight patients with Fabry disease (mean age, 46 years ± 14 [standard deviation]; 63% female) who underwent TTE and cardiac MRI within a 6-month interval between 2008 and 2018 were included in this retrospective cohort study. The clinical significance of measurement discrepancies was evaluated with respect to diagnosis of left ventricular hypertrophy (LVH), eligibility for disease-specific therapy, and prognosis. Statistical analysis included paired-sample t test, Cox proportional hazard models, Akaike information criterion (AIC), and intraclass correlation coefficients. RESULTS: LVM indexed to body surface area (LVMI) and MWT were significantly higher at TTE compared with MRI (105 g/m2 ± 48 vs 78 g/m2 ± 36, P < .001 and 14 mm ± 4 vs 13 mm ± 5, P = .008, respectively). LVH classification was discordant between modalities in 23 patients (29%) (P < .001). Eligibility for disease-specific therapy based on MWT was discordant between modalities in 20 patients (26%) (P < .001). LVMI assessed with MRI was a better predictor of the combined endpoint compared with LVMI assessed with TTE (AIC, 127 vs 131). Interobserver agreement for LVMI and MWT was higher for MRI (intraclass correlation coefficient, 0.951 and 0.912, respectively) compared with TTE (intraclass correlation coefficient, 0.940 and 0.871; respectively). CONCLUSION: TTE overestimates LVM and MWT and has lower reproducibility compared with cardiac MRI in Fabry disease. Measurement discrepancies between modalities are clinically significant with respect to diagnosis of LVH, prognosis, and treatment decisions.© RSNA, 2020.

Cardiac MRI measurements of pericardial adipose tissue volumes in patients on in-centre nocturnal hemodialysis.

BACKGROUND: Conversion from conventional hemodialysis (CHD) to in-centre nocturnal hemodialysis (INHD) is associated with left ventricular (LV) mass regression, but the underlying mechanisms are not fully understood. Using cardiac MRI (CMR), we examined the effects of INHD on epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT), and the relationships between EAT, PAT and LV remodeling, biomarkers of nutrition, myocardial injury, fibrosis and volume. METHODS: We conducted a prospective multicenter cohort study of 37 patients transitioned from CHD to INHD and 30 patients on CHD (control). Biochemical markers and CMR were performed at baseline and 52 weeks. CMR images were analyzed by independent readers, blinded to order and treatment group. RESULTS: Among 64 participants with complete CMR studies at baseline (mean age 54; 43% women), there were no significant differences in EAT index (60.6 ± 4.3 mL/m2 vs 64.2 ± 5.1 mL/m2, p = 0.99) or PAT index (60.0 ± 5.4 mL/m2 vs 53.2 ± 5.9 mL/m2, p = 0.42) between INHD and CHD groups. Over 52 weeks, EAT index and PAT index did not change significantly in INHD and CHD groups (p = 0.21 and 0.14, respectively), and the changes in EAT index and PAT index did not differ significantly between INHD and CHD groups (p = 0.30 and 0.16, respectively). Overall, changes in EAT index inversely correlated with changes in LV end-systolic volume index (LVESVI) but not LV end-diastolic volume index (LVEDVI), LV mass index (LVMI), and LV ejection fraction (LVEF). Changes in PAT index inversely correlated with changes in LVESVI, LVMI and positively correlated with changes in LVEF. There were no correlations between changes in EAT index or PAT index with changes in albumin, LDL, triglycerides, troponin-I, FGF-23, or NT-proBNP levels over 52 weeks (all p > 0.30). CONCLUSIONS: INHD was not associated with any changes in EAT index and PAT index over 12 months. Changes in EAT index were not significantly associated with changes in markers of LV remodeling, nutrition, myocardial injury, fibrosis, volume status. In contrast, changes in PAT index, which paradoxically is expected to exert less paracrine effect on the myocardium, were correlated with changes in LVESVI, LVMI and LVEF. Larger and longer-term studies may clarify the role of PAT in cardiac remodeling with intensified hemodialysis. CLINICALTRIALS. GOV IDENTIFIER: NCT00718848.