Pulmonary Regurgitation Fraction Research Articles

Cardiac Magnetic Resonance in long term follow-up of Tetralogy of Fallot

Tetralogy of Fallot (TOF) is the most frequent cyanotic congenital heart disease. Pulmonary regurgitation (PR) and right ventricle (RV) enlargement and dysfunction are the most common long-term complications. Cardiac magnetic resonance (CMR) is the gold standard for RV evaluation. To analyze CMR results in the follow-up of TOF patients. All CMR performed between 2007 and 2012 in TOF patients with transannular patch (TAP) repair or infundibular widening, and without pulmonary valve replacement (PVR) were included. Pulmonary regurgitant fraction (PRF), ventricular end-diastolic (EDV) and end-systolic volume (ESV), and ejection fraction (EF) were examined. 122 CMR were performed in 114 patients. Average age at CMR was 15.4±7.4 years. 53.3% of them presented severe PR (> 40%). RVEDV was 157.3 ± 38.6 ml/m2, RVESV was 85.3 ± 27 ml/m2 and RVEF was 46.4 ± 7.1%. RVEDV was > 150 ml/ m2 in 48.4% and > 170 ml/m2 in 32.8% of patients. Patients with TAP showed larger RV volumes compared with those with infundibular widening. RVEDV > 170 ml/m2 showed worse RVEF that those with lower RVEDV (47.9 ± 7% vs 43.2 ± 6.4%, p < 0.01). Almost half of the pa tients showed significant RV enlargement, demonstrating that the indication of CMR is late in their follow-up. TAP was associated with higher RVEDV and RVESV, but no worse RVEF.

Abnormal biventricular performance in asymptomatic adolescents late after repaired Tetralogy of Fallot: Combined two-dimensional speckle tracking and three-dimensional echocardiography study

BackgroundThe aim of this prospective study was to assess biventricular performance in asymptomatic adolescents with repaired tetralogy of Fallot (TOF) using 2D speckle tracking and real time 3D echocardiography simultaneously. MethodsWe studied 31 patients with repaired TOF (M/F: 22/9, age: 16.1 ± 6.1 yrs) who had history of cardiac surgery with mean follow-up duration of 12.8 years, and 32 age- and sex-matched normal individuals (M/F: 23/9, age: 16.6 ± 5.1 yrs). All subjects underwent speckle tracking and 3D echocardiography, electrocardiogram, treadmill, and blood sampling for measurement of brain natriuretic peptide (BNP). ResultsCompared to the control group, the TOF group had higher BNP level (31.8 ± 21.4 vs 14.1 ± 12.4 pg/ml, p < 0.01), lower peak oxygen consumption (8.4 ± 1.7 vs 9.9 ± 1.6 ml/kg/min, p < 0.05), and longer QRS duration (126 ± 30 vs 82 ± 9 ms, p < 0.01). Patients with repaired TOF had significantly impaired right ventricle (RV) global and all six regional longitudinal strain and strain rate than normal controls. Left ventricle (LV) global and mainly apical regional longitudinal strain and strain rate were reduced in patients with repaired TOF. There was a significant correlation of global longitudinal strain (r = 0.456, p = 0.01) and global time to peak longitudinal strain (r = 0.484, p < 0.01) between LV and RV in patients with repaired TOF. In terms of 3D echo cardiographic volume data, patients with repaired TOF had lower LV stroke volume index (p < 0.05), but higher RV end diastolic volume index (p < 0.01), RV end systolic volume index (p < 0.01), RV stroke volume index (p < 0.01), and pulmonary regurgitation fraction (p < 0.01) than normal controls. ConclusionOur results suggest asymptomatic adolescents with repaired TOF had abnormal biventricular myocardial performance, as demonstrated by combined 2D speckle-tracking and 3D echocardiography. The implications of these findings for management of adolescents late after repaired TOF remain to be determined.

Abstract 21055: Baseline Cardiovascular Magnetic Resonance Imaging Measurements Are Associated With Clinical Outcomes at Three Years of Follow-Up: Results From a Prospective, International, Multi-Site Study of Patients With Significant Pulmonary Regurgitation Late After Tetralogy of Fallot Repair

Introduction: Late complications after tetralogy of Fallot repair (rTOF) often arise from chronic pulmonary regurgitation (PR). Prospective studies of outcomes in those with rTOF and significant PR are lacking. Hypothesis: We hypothesized that cardiovascular magnetic resonance imaging (CMR) imaging measurements would be associated with poor outcomes in an “at risk” population with rTOF and ≥moderate PR. Methods: This was a prospective, international study (North America, Europe and Asia) of children and adults. Inclusion criteria were rTOF in childhood, age ≥12 years, ≥moderate PR, and CMR within 18 months of enrollment. All CMR analysis occurred in a central core laboratory. Patient reported outcomes were collected using standardized tools. The primary clinical outcome was death or sustained (&gt;30 seconds) ventricular tachycardia (VT) recorded at 3 year follow-up. Results: We enrolled 629 patients (55% male) at 29±14 years (2013-2017). Primary rTOF was done at 1.6 years (IQR 0.6,4.2) with a transannular patch in 55%. By standardized symptom assessment, 78% were asymptomatic (NYHA 1). Baseline CMR findings included PR fraction 38±14%, right ventricular (RV) end-diastolic volume indexed (EDVi) 155±41mL/m2, RV ejection fraction (EF) 44±7%, RV mass indexed 59±16 g/m2, left ventricular (LV) EDVi 85±18mL/m2, LVEF 55±7% and LV mass indexed 88±27 g/m2. Outcomes at 3 years were recorded (available in n=101). During follow-up, surgical pulmonary valve replacement (PVR) occurred in 38 patients (38%). In the PVR group compared with the non-PVR group, baseline RVEDVi was larger (189 vs. 152 mL/m2, p&lt;0.0001) and RV mass was higher (65 vs. 58 g/m2, p=0.04); RVEF, LVEF and LV mass did not differ between groups. At 3 year follow-up, 4 patients (4%) had an outcome (n=2 deaths, n=2 VT) and half of these patients (n=2) had PVR. Those with outcomes had higher baseline RV mass and LV mass as compared to those without outcomes (73±12 vs. 59±13g/m2, p=0.04 and 132±32 vs. 89±28g/m2, p=0.01); volumes and function did not differ between groups. Conclusions: Despite significant PR, most patients with rTOF were asymptomatic. At 3 year follow-up, PVR occurred in more than one third of patients. Death or VT was observed in a small number of patients who had higher RV and LV mass on baseline CMR.

PO17-64 - Haemodynamic, ventilatory and peripheral determinants during exercice of repaired tetralogy of fallot

Background Pulmonary valve replacement (PVR) for patients with repaired Tetralogy of Fallot (TOF) and pulmonary regurgitation (PR) improves functional status without definitive improvement of peak VO2 despite correction of the haemodynamic lesion. We aim to study cardiorespiratory and peripheral profiles during exercise test before and after PVR to understand this improvement. Methods Patients with TOF and severe PR performed a cardiopulmonary exercise testing (CPET) and a cardiac MRI for the measurement of ventricular volumes and pulmonary regurgitation fraction (FR) before and after PVR. Results Fifteen patients (mean age 33 ± 13 years) were included. CPET was performed 6 months before and 25 ± 2 months after PVR. Following PVR: significant improvement in NYHA functional class (P = 0,006) without significant improvement in peak VO2 (26 ± 6 to 25 ± 6,9 mL/kg/min, P = 0,36) nor maximal workload (114 ± 30 to 118 ± 30 Watt, P = 0,31) with unchanged maximal heart. Patients had a moderate hyperventilation without pejorative criterion (VE/VCO2 nadir 31 ± 3 to 32 ± 7, P = 0,61) without pulmonary limitation (maximal breathing reserve 31 ± 23 to 21 ± 17%, P = 0,27) despite a restrictive pattern in spirometric results. Nevertheless, we found a significant improvement in peak oxygen pulse (9,9 ± 2,5 to 11 ± 4, P = 0,04) and a significant postponed ventilatory anaerobic threshold (VAT) after PVR (05:28 ± 2:00 to 6:57 ± 1:53 min, P = 0,002; 61 ± 20 to 75 ± 18 Watt, P = 0,006). PR (FR: 46 ± 14 to 5,6± 9,7%, P Conclusion Despite the lack of improvement in the peak VO2, hemodynamic improvement was observed by the significant improvement in oxygen pulse and peripheral capacity associated with an improvement in functional capacity. It can be assumed that the peak VO2 is not the best marker for the evaluation of aerobic capacity and that our evaluation could be based on the VAT in these patients.

Quantification of Pulmonary Regurgitation by Vector Flow Mapping in Congenital Heart Patients after Repair of Right Ventricular Outflow Obstruction: A Preliminary Study

Vector flow mapping (VFM) enables direct visualization of flow pattern and estimation of flow volume. The aim of this study was to determine its accuracy in the quantification of pulmonary regurgitation (PR) in congenital heart patients after repair of right ventricular (RV) outflow obstruction. This study comprised two parts: (1) validation of VFM in the quantification of PR in patients with repaired tetralogy of Fallot by cardiac magnetic resonance and (2) clinical application of VFM to determine PR in patients after biventricular repair of pulmonary atresia and stenosis with intact ventricular septum. PR was quantified by calculation of VFM-derived pulmonary regurgitant ratio (PRVFM), defined as ratio of backward to forward flow volume. Coefficients of variations for intra- and interobserver variability in the measurements of PRVFM were 7.0% and 10.4%, respectively. Fourteen patients with repaired tetralogy of Fallot aged 31.3±7.3years were studied. Their PRVFM correlated strongly with cardiac magnetic resonance-derived PR fraction (r=0.95, P<.001) and RV end-diastolic volume (r=0.84, P<.001). In the second part, 14 patients with pulmonary atresia with intact ventricular septum aged 25.6±6.0years, 14 patients with pulmonary stenosis aged 24.2±7.0years, and 14 healthy control subjects were studied. PRVFM was found to increase across groups of subjects with absent (4.6±3.3%), mild (11.1±7.1%), moderate (29.6±7.8%), and severe (50.1±8.2%) PR as defined semiquantitatively by color flow mapping. Furthermore, PRVFM correlated strongly with the ratio of PR color jet to width of RV outflow (r=0.92, P<.001). VFM is a reproducible technique for accurate quantification of PR in congenital heart patients after repair of RV outflow obstruction.

Cardiac magnetic resonance indices reflecting pulmonary regurgitation burden after tetralogy of Fallot repair

To investigate cardiac magnetic resonance (CMR)-derived parameters to determine a convenient index reflecting the degree of pulmonary regurgitation (PR) after Tetralogy of Fallot (TOF) repair. Sixty-three patients (age at CMR study, 23.6 [10.2-34.7] years, 55.6% male) underwent CMR after TOF repair. PR was quantified using ventricular stroke volume difference and phase-contrast mapping of the main pulmonary artery flow. In both approaches, the PRV index (PRVI) and the PR fraction (PRF) were calculated and correlated to the right ventricle end-diastolic volume index (RVEDVI) and the right ventricle end-systolic volume index (RVESVI). No statistically significant difference was observed between the PR volumes and the PRF measured by the stroke volume difference or the phase-contrast method. The PRVI was better correlated to RVEDVI and RVESVI than the PRF. The PRVI exhibits more correlation to the RVEDVI than PRF. Thus, it could be a preferable parameter to reflect the PR burden.

Diagnostic value of Doppler echocardiography for identifying hemodynamic significant pulmonary valve regurgitation in tetralogy of Fallot: comparison with cardiac MRI

Quantification of pulmonary regurgitation (PR) is essential in the management of patients with repaired tetralogy of Fallot (TOF). We sought to evaluate the accuracy of first-line Doppler echocardiography in comparison with cardiac magnetic resonance imaging (MRI) to identify hemodynamic significant PR. Paired cardiac MRI and echocardiographic studies (n = 97) in patients with repaired TOF were retrospectively analyzed. Pressure half time (PHT) and pulmonary regurgitation index (PRi) were measured using continuous wave Doppler. The ratio of the color flow Doppler regurgitation jet width to pulmonary valve (PV) annulus (jet/annulus ratio) and diastolic to systolic time velocity integral (DSTVI; pulsed wave Doppler) were assessed. Accuracy of echocardiographic measurements was tested to identify significant PR as determined by phase-contrast MRI (PR fraction [PRF] ≥ 20%). Mean PRF was 29.4 ± 15.7%. PHT < 100 ms had a sensitivity of 93%, specificity 75%, positive predictive value (PPV) 92% and negative predictive value (NPV) 78% for identifying significant PR (C-statistic 0.82). PRi < 0.77 had sensitivity and specificity of 66% and 54%, respectively (C-statistic 0.63). Jet/annulus ratio ≥1/3 had sensitivity 96%, specificity 75%, PPV 92% and NPV 82% (C-statistic 0.87). DSTVI had sensitivity 84%, specificity 33%, PPV 84% and NPV 40%, (C-statistic 0.56). Combined jet/annulus ratio ≥1/3 and PHT < 100 ms was highly accurate in identifying PRF ≥ 20%, with sensitivity 97% and specificity 100%. PHT and jet/annulus ratio on Doppler echocardiography, especially when combined, are highly accurate in identifying significant PR and therefore seem useful in the follow-up of patients with repaired TOF.

Quantification of pulmonary regurgitation in patients with repaired Tetralogy of Fallot by 2D phase-contrast MRI: Differences between the standard method of velocity averaging and a pixel-wise analysis.

ObjectivesTo compare the values of pulmonary regurgitation in patients with repaired Tetralogy of Fallot quantified from two-dimensional phase-contrast data, by using a new pixel-wise analysis and the standard velocity-averaging method.DesignQuantitative in silico and in vivo analysis.SettingHospital Sótero del Río. The magnetic resonance images were acquired using a Philips Achieva 1.5T scanner.ParticipantsTwenty-five patients with repaired Tetralogy of Fallot who underwent cardiovascular magnetic resonance imaging requested by their referring physicians were included in this study.Main outcome measuresUsing a computational fluid dynamics simulation, we validated our pixel-wise method, quantifying the error of our method in comparison with the standard method. The patients underwent a standard two-dimensional phase-contrast magnetic resonance imaging acquisition for quantifying pulmonary artery flow. Pulmonary regurgitation fraction was estimated by using our pixel-wise and the standard method. The two-dimensional flow profiles were inspected looking for simultaneous antegrade and retrograde flows in the same cardiac phase. Statistical analysis was performed with t-test for related samples, Bland–Altman plots, and Pearson correlation coefficient.ResultsEstimation of pulmonary regurgitation fraction using the pixel-wise analysis revealed higher values compared with the standard method (39 ± 16% vs. 30 ± 22%, p-value <0.01). Eight patients (32%) had a difference of more than 10% between methods. Analysis of two-dimensional flow profiles in these patients revealed simultaneous antegrade and retrograde flows through the pulmonary artery during systole–early diastole.ConclusionQuantification of pulmonary regurgitation fraction in patients with repaired Tetralogy of Fallot through a pixel-wise analysis yields higher values of pulmonary regurgitation compared with the standard velocity-averaging method.

Sustained Improvement in Right Ventricular Chamber Dimensions 10 Years Following Xenograft Pulmonary Valve Replacement.

The goals following pulmonary valve replacement (PVR) are to optimize right ventricular hemodynamics and minimize the need for subsequent reoperations on the right ventricular outflow tract. We hypothesized PVR using a xenograft valved conduit would result in superior freedom from reoperation with sustained improvement in right ventricular chamber dimensions. Xenograft valved conduits placed in patients aged >16 years were reviewed from 2000 to 2010 to allow for a 5-year minimum follow-up. Preoperative, one-year, and the most recent echocardiograms quantified right ventricular chamber dimensions, corresponding Z scores, and prosthetic valve function. Magnetic resonance imaging (MRI) studies compared preoperative and follow-up right ventricular volumes. A total of 100 patients underwent PVR at 24 (19-34) years. Freedom from reintervention was 100% at 10 years. At most recent follow-up, only one patient had greater than mild pulmonary insufficiency. The one-year (17.3 ± 7.2 mm Hg; P < .01) and most recent follow-up (18.6 ± 9.8 mm Hg; P < .01) Doppler-derived right ventricular outflow tract gradients remained significantly lower than preoperative measurements (36.7 ± 27.0 mm Hg). Similarly, right ventricular basal diameter, basal longitudinal diameter, and the corresponding Z scores remained lower at one year and follow-up from preoperative measurements. From 34 MRI studies, the right ventricular end-diastolic indexed volume (161.7 ± 58.5 vs 102.9 ± 38.3; P < .01) and pulmonary regurgitant fraction (38.0% ± 15.9% vs 0.8% ± 3.3%; P < .01) were significantly lower at 7.1 ± 3.4 years compared to the preoperative levels. Use of a xenograft valved conduit for PVR results in excellent freedom from reoperation with sustained improvement in right ventricular dimensions at an intermediate-term follow-up.

Evolution of right ventricular size over time after tetralogy of Fallot repair: a longitudinal cardiac magnetic resonance study

It is commonly believed that pulmonary regurgitation (PR) after surgical repair of tetralogy of Fallot (TOF) leads to progressive right ventricular (RV) enlargement. However, progressive RV dilatation has never clearly been documented in this patient population. Therefore, we studied the size of the RV over time in patients after surgical TOF repair. Fifty-one consecutive patients after surgical TOF repair underwent at least two cardiovascular magnetic resonance (CMR) exams using a single CMR scanner. Patients with RV outflow tract obstruction, interventions other than the initial repair and CMR exams with use of sedation were excluded. Three subgroups with different repair techniques were studied: transannular patch repair [n = 22, age 17 ± 10 years], subvalvular patch repair [n = 15, age 22 ± 8 years], or non-patch repair/infundibulectomy (n = 14, age 28 ± 11 years). Right ventricular end-diastolic volume index (RVEDVI) and PR fraction did not change during the 37 ± 21 months follow-up between first and last CMR in the whole group (RVEDVI: 118 ± 23 mL/m2 vs. 119 ± 23 mL/m2, P = 0.720; PR fraction: 33% (23-40%) vs. 32% (24-39%), P = 0.268). RVEDVI remained stable in all subgroups (transannular patch: 120 ± 21 mL/m2 vs. 122 ± 22 mL/m2, subvalvular patch: 112 ± 23 mL/m2 vs. 111 ± 23 mL/m2, non-patch: 123 ± 28 mL/m2 vs. 123 ± 23 mL/m2, P = 0.827). RVEDVI at last CMR did not differ between groups (P = 0.301). This study shows no progression of RV dilatation in patients after surgical repair of TOF with moderately dilated RVs and significant PR during a 3-year follow-up. RV dilatation in our patient group seems to be independent from surgical repair techniques.

Longitudinal changes in adolescents with TOF: implications for care

We sought to identify predictors of change in right ventricular function and exercise capacity in adolescents following repair for tetralogy of Fallot. We performed a longitudinal study with serial cardiac magnetic resonance imaging and/or exercise stress tests. Patients with interim intervention on the pulmonary valve were excluded. Paired t-test was used to detect longitudinal changes and multivariable regression models were built to identify predictors of change. Initial and follow up magnetic resonance and exercise stress test studies were available for 65 and 63 subjects, respectively. Age at initial testing was 11.7 ± 2.7 years. Average follow up time was 4.5 ± 1.8 (magnetic resonance) and 4.0 ± 1.6 (exercise test) years. There was a significant increase in right ventricular end diastolic and systolic volume (119 ± 34 to 128 ± 35 ml/m2, P = 0.006; 49 ± 20 to 56 ± 23 ml/m2, P = 0.001, respectively), and a decrease in right ventricular ejection fraction (60 ± 7 to 56 ± 8%, P = 0.001), with no significant change in pulmonary regurgitant fraction or right ventricular cardiac index. Predictors of right ventricular dilation over time included: time elapsed from surgical repair, severity of pulmonary insufficiency and right ventricular dilation at the initial magnetic resonance imaging. Of those, time elapsed from surgical repair had the most significant effect. There was no change in exercise capacity. In the adolescent with tetralogy of Fallot, longer time from surgery, more pulmonary insufficiency and greater right ventricular dilation at initial magnetic resonance imaging are associated with progressive right ventricular dilation. These results suggest early monitoring with magnetic resonance imaging might identify those at highest risk for progressive disease.

NT-proBNP as Marker of Ventricular Dilatation and Pulmonary Regurgitation After Surgical Correction of Tetralogy of Fallot: A MRI Validation Study.

The goal of this study is to evaluate whether NT-proBNP plasma levels may help as a screening biomarker for monitoring right ventricular dilatation, pulmonary regurgitation and the onset of heart failure in patients with repaired Tetralogy of Fallot. Our single-centre observational prospective study involved 43 patients (15.1years, SD=8) with corrected Tetralogy of Fallot. Data collection included: clinical parameters (electrocardiogram, chest X-ray, NYHA scale, time since last surgery), biochemistry (NT-proBNP levels) and MRI values (ventricular volumetry, pulmonary flow assessment). Mean time since last surgery was 13.5years (SD=7.8). There was a statistically significant correlation between the NT-proBNP levels (187.4pg/ml, SD=154.9) and right ventricular dilatation for both the right ventricular end-diastolic volume (124.9ml/m2, SD=31.2) (Pearson=0.19, p<0.01) and end-systolic volume (56.1ml/m2, SD=18.8) (Pearson=0.21, p<0.01) and also with the pulmonary regurgitation fraction (36.5%, SD=16, Pearson=0.12, p<0.01). No significant correlation was found between NT-proBNP and right ventricular ejection fraction (54.6%, SD=10.6, Pearson=-0.07), left ventricular ejection fraction (59.9%, SD=7.1, Pearson=-0.18) or any clinical parameters. The receiver operating curve analysis evidenced that a NT-proBNP cut-off value above 133.2pg/ml predicted the presence of dilated right ventricular end-diastolic and end-systolic volumes over centile 95 (sensitivity 82 and 83% and specificity 93 and 79%, respectively). In conclusion, in patients with surgically corrected Tetralogy of Fallot, NT-proBNP levels correlate with right ventricular dilatation and the degree of pulmonary regurgitation. Ambulatory determination of NT-proBNP might be an easy, readily available and cost-effective alternative for MRI follow-up evaluation of these patients.

Abstract 13145: Ventriculoarterial Coupling Ratio is Associated With Adverse Outcomes in Repaired Tetralogy of Fallot

Introduction: Patients with repaired tetralogy of Fallot (TOF) are at risk of premature death and ventricular arrhythmias. The ventriculoarterial coupling (VAC) ratio, the ratio of arterial elastance (Ea) and ventricular end-systolic elastance (Ees), is a measure of cardiac efficiency. Little is known about the VAC ratio in this population. We used a previously described cardiac magnetic resonance (CMR) method to measure right and left VAC ratios in patients with repaired TOF, and assessed the hypothesis that this is related to outcomes. Methods and Results: We measured VAC from CMR data at a single institution on 593 TOF patients (age 21.5 ± 14.4 years) and 58 controls (age 13.2 ± 4.0 years). Frequency matching based on age and gender yielded 326 TOF patients to compare with controls. VAC ratio was calculated for both right (RV) and left (LV) ventricles as Ea/Ees = end-systolic volume/stroke volume. TOF patients had higher RV and LV VAC ratios (p&lt;0.001) (RV results, figure A). Within the TOF cohort, RV VAC ratio correlated positively with LV VAC (r=0.43, p&lt;0.001), but not with pulmonary regurgitation fraction. After a median follow-up of 5.0 (IQR 2.4-8.5) years, 26 patients (4.4%) reached a composite endpoint of death (n=16), aborted sudden cardiac death (n=5), or sustained ventricular tachycardia (VT, n=5). An RV VAC ratio in the highest tertile (T3) was associated with higher risk of the outcome (p&lt;0.001, figure B). Controlling for known risk factors (RV mass-to-volume ratio, atrial arrhythmia and non-sustained VT), an RV VAC ratio ≥1.11 (highest tertile) was independently associated with the composite outcome (hazard ratio 7.3, 95% CI 2.7-19.9, p&lt;0.001). Conclusion: In this cohort, TOF patients demonstrated inefficient VAC as compared with controls. A higher RV VAC ratio was independently associated with the composite outcome of death, aborted sudden cardiac death, or sustained VT. Further investigation of the significance of VAC in this population is warranted.

Longitudinal Validation of the Diastolic to Systolic Time-Velocity Integral Ratio as a Doppler-Derived Measure of Pulmonary Regurgitation in Patients with Repaired Tetralogy of Fallot.

Pulmonary regurgitation (PR) is a common residual lesion and major determinant of outcome following surgical repair for tetralogy of Fallot. We sought to longitudinally study a previously described echocardiographic index as a correlate of PR measured by cardiac magnetic resonance imaging (CMR). We conducted a retrospective longitudinal study of patients with baseline and follow-up echocardiogram and CMR. The baseline studies were obtained as part of a research protocol, while the follow-up studies were performed for clinical purposes. On echocardiogram, the ratio of diastolic and systolic time-velocity integrals (DSTVI) in the main pulmonary artery was calculated. The Wilcoxon matched-pairs signed-rank test was used to test for individual changes in PR on echocardiogram and CMR. A linear regression of pulmonary valve regurgitant fraction (RF) was fit on DSTVI to identify clinically meaningful cut points of DSTVI. Thirty-five subjects were included, age at follow-up 18.3±3.5years. The follow-up between consecutive CMRs was a median time of 60months (interquartile range 46-73). There was a moderate correlation between DSTVI and PR measured as RF by CMR (r=0.62, p=0.0001). A CMR RF of 20 and 40% (the boundaries between mild/moderate and moderate/severe PR) corresponded with DSTVI of 0.52 and 0.79 (95% CI 0.39; 0.66, and 0.69; 89), respectively. There was no significant change in either DSTVI (p=0.61) or PR (p=0.89) from baseline to follow-up. This study lends further credence to the DSTVI as an accurate reflection of PR. This index might become helpful in the routine echocardiographic assessment of PR. Further studies are needed to determine whether changes in RF by CMR result in changes in DSTVI.

Implantation of the Medtronic Harmony Transcatheter Pulmonary Valve Improves Right Ventricular Size and Function in an Ovine Model of Postoperative Chronic Pulmonary Insufficiency.

Pulmonary insufficiency is the nexus of late morbidity and mortality after transannular patch repair of tetralogy of Fallot. This study aimed to establish the feasibility of implantation of the novel Medtronic Harmony transcatheter pulmonary valve (hTPV) and to assess its effect on pulmonary insufficiency and ventricular function in an ovine model of chronic postoperative pulmonary insufficiency. Thirteen sheep underwent baseline cardiac magnetic resonance imaging, surgical pulmonary valvectomy, and transannular patch repair. One month after transannular patch repair, the hTPV was implanted, followed by serial magnetic resonance imaging and computed tomography imaging at 1, 5, and 8 month(s). hTPV implantation was successful in 11 animals (85%). There were 2 procedural deaths related to ventricular fibrillation. Seven animals survived the entire follow-up protocol, 5 with functioning hTPV devices. Two animals had occlusion of hTPV with aneurysm of main pulmonary artery. A strong decline in pulmonary regurgitant fraction was observed after hTPV implantation (40.5% versus 8.3%; P=0.011). Right ventricular end diastolic volume increased by 49.4% after transannular patch repair (62.3-93.1 mL/m2; P=0.028) but was reversed to baseline values after hTPV implantation (to 65.1 mL/m2 at 8 months, P=0.045). Both right ventricular ejection fraction and left ventricular ejection fraction were preserved after hTPV implantation. hTPV implantation is feasible, significantly reduces pulmonary regurgitant fraction, facilitates right ventricular volume improvements, and preserves biventricular function in an ovine model of chronic pulmonary insufficiency. This percutaneous strategy could potentially offer an alternative for standard surgical pulmonary valve replacement in dilated right ventricular outflow tracts, permitting lower risk, nonsurgical pulmonary valve replacement in previously prohibitive anatomies.

Predictors of Change in Functional Health Status in Adults with Repaired Tetralogy of Fallot.

Left ventricular (LV) ejection fraction (EF) and right ventricular (RV) ejection fraction by cardiovascular magnetic resonance (CMR) are associated with functional health status in patients with repaired tetralogy of Fallot (TOF) in cross-sectional studies, but few longitudinal data are available. This study aimed to determine predictors of subsequent decrease in functional health status in midterm follow-up. Patients with repaired TOF who had previously completed CMR and assessment with the Short Form 36 version 2 (SF-36) were recruited for repeat CMR, SF-36, and exercise test, if they had not had interval pulmonary valve replacement (PVR). Patients from the same cohort who had undergone PVR were recruited for repeat SF-36. A total of 19 patients (median 33.5years old, interquartile range [IQR] 26-42years, 53% male) had not undergone PVR and were enrolled at a median of 5.0years (IQR 4.8-5.3) since prior CMR and SF-36. LVEF and RVEF did not change from baseline, while RV end-diastolic volume increased (138±34 vs. 126±31ml/m(2), p=0.02). In the overall cohort, SF-36 scores remained stable. However, higher baseline RV end-systolic volume and pulmonary regurgitant fraction correlated with subsequent decreases in SF-36 scores. In 9 patients post-PVR (median 35.9years old, IQR 24-43), physical functioning increased compared to those without PVR (change in z-score +0.59±0.59 vs. -0.26±0.72, p=0.005). In adults with repaired TOF who do not undergo PVR, LVEF, RVEF, and functional health status remain stable in midterm follow-up. However, baseline RV end-systolic volume correlates with subsequent change in functional health status, underscoring its importance in prognostication and timing of intervention in this population.

Assessing Late Cardiopulmonary Function in Patients with Repaired Tetralogy of Fallot Using Exercise Cardiopulmonary Function Test and Cardiac Magnetic Resonance.

Patients with repaired tetralogy of Fallot (TOF) usually experience progressive right ventricle (RV) dysfunction due to pulmonary regurgitation (PR). This could further worsen the cardiopulmonary function. This study aimed to compare the changes in patient exercise cardiopulmonary test and cardiac magnetic resonance imaging, and consider the implication of these changes. Our study examined repaired TOF patients who underwent cardiopulmonary exercise test (CPET) to obtain maximal (peak oxygen consumption, peak VO2) and submaximal parameters (oxygen uptake efficiency plateau, oxygen uptake efficiency plateau (OUEP), and ratio of minute ventilation to carbon dioxide production, VE/VCO2 slope). Additionally, the hemodynamic status was assessed by using cardiac magnetic resonance. Criteria for exclusion included TOF patients with pulmonary atresia, atrioventricular septal defect, or absence of pulmonary valve syndrome. We enrolled 158 patients whose mean age at repair was 7.8 ± 9.1 years (range 0.1-49.2 years) and the mean patient age at CPET was 29.5 ± 12.2 years (range 7.0-57.0 years). Severe PR (PR fraction ≥ 40%) in 53 patients, moderate in 55, and mild (PR fraction < 20%) in 50 patients were noted. The mean RV end-diastolic volume index (RVEDVi) was 113 ± 35 ml/m(2), with 7 patients observed to have a RVEDVi > 163 ml/m(2). The mean left ventricular ejection fraction (LVEF) was 63 ± 8%, left ventricular end-diastolic volume index (LVEDVi) was 65 ± 12 ml/m(2), and LVESVi was 25 ± 14 ml/m(2). CPET revealed significantly decreased peak VO2 (68.5 ± 14.4% of predicted), and fair OUEP (90.3 ± 14.1% of predicted) and VE/VCO2 slope (27.1 ± 5.3). PR fraction and age at repair were negatively correlated with maximal and submaximal exercise indicators (peak VO2 and OUEP). Left ventricular (LV) function and size were positively correlated with peak VO2 and OUEP. The results of CPET showed that patients with repaired TOF had a low maximal exercise capacity (peak VO2), but a fair submaximal exercise capacity (OUEP and VE/VCO2 slope), suggesting limited exercise capability in high intensity circumstances. PR, LV function and age at total repair were the most important determinants of CPET performance. Cardiac magnetic resonance; Cardiopulmonary exercise function; Pulmonary regurgitation; Surgical age; Tetralogy of Fallot.

Predictors of change in functional health status in adults with repaired tetralogy of Fallot

Left ventricular (LV) ejection fraction (EF) and right ventricular (RV) ejection fraction by cardiovascular magnetic resonance (CMR) are associated with functional health status in patients with repaired tetralogy of Fallot (TOF) in cross-sectional studies, but few longitudinal data are available. This study aimed to determine predictors of subsequent decrease in functional health status in midterm follow-up. Patients with repaired TOF who had previously completed CMR and assessment with the Short Form 36 version 2 (SF-36) were recruited for repeat CMR, SF-36, and exercise test, if they had not had interval pulmonary valve replacement (PVR). Patients from the same cohort who had undergone PVR were recruited for repeat SF-36. A total of 19 patients (median 33.5 years old, interquartile range [IQR] 26–42 years, 53 % male) had not undergone PVR and were enrolled at a median of 5.0 years (IQR 4.8–5.3) since prior CMR and SF-36. LVEF and RVEF did not change from baseline, while RV end-diastolic volume increased (138 ± 34 vs. 126 ± 31 ml/m2, p = 0.02). In the overall cohort, SF-36 scores remained stable. However, higher baseline RV end-systolic volume and pulmonary regurgitant fraction correlated with subsequent decreases in SF-36 scores. In 9 patients post-PVR (median 35.9 years old, IQR 24–43), physical functioning increased compared to those without PVR (change in z-score +0.59 ± 0.59 vs. −0.26 ± 0.72, p = 0.005). In adults with repaired TOF who do not undergo PVR, LVEF, RVEF, and functional health status remain stable in midterm follow-up. However, baseline RV end-systolic volume correlates with subsequent change in functional health status, underscoring its importance in prognostication and timing of intervention in this population.

Increased left ventricular myocardial extracellular volume is associated with longer cardiopulmonary bypass times, biventricular enlargement and reduced exercise tolerance in children after repair of Tetralogy of Fallot

BackgroundUnfavorable left ventricular (LV) remodelling may be associated with adverse outcomes after Tetralogy of Fallot (TOF) repair. We sought to assess T1 cardiovascular magnetic resonance (CMR) markers of diffuse LV myocardial fibrosis in children after TOF repair, and associated factors.MethodsIn this prospective, cross-sectional study, native (=non-contrast) T1 times and extracellular volume fraction (ECV) were quantified in the LV myocardium using CMR. Results were related to ventricular volumes and function, degree of pulmonary regurgitation, as well as surgical characteristics, and exercise capacity.ResultsThere was no difference in native T1 times or ECV between 31 TOF patients (age at CMR 13.9 ± 2.4 years, 19 male) and 15 controls (age at CMR 13.4 ± 2.6 years, 7 male). Female TOF patients had higher ECVs than males (25.2 ± 2.9 % versus 22.7 ± 3.3 %, p < 0.05). In the patient group, higher native T1 and ECV correlated with higher Z-Scores of right and left ventricular end-diastolic volumes, but not with reduced left and right ventricular ejection fraction or higher pulmonary regurgitation fraction. Longer cardiopulmonary bypass and aortic cross clamp times at surgery correlated with increased native T1 times and ECVs (r = 0.48, p < 0.05 and r = 0.65, p < 0.01, respectively). Maximum workload (percent of predicted for normal) correlated inversely with ECV (r = -0.62, p < 0.05). Higher native T1 times correlated with worse LV longitudinal (r = 0.50, p < 0.05) and mid short axis circumferential strain (r = 0.38, p < 0.05).ConclusionsAs compared to controls, TOF patients did not express higher markers of diffuse fibrosis. Longer cardiopulmonary bypass and aortic cross clamp times at surgery as well as biventricular enlargement and reduced exercise tolerance are associated with markers of diffuse myocardial fibrosis after TOF repair. Female patients have higher markers of diffuse myocardial fibrosis than males.

Serum Bile Acids in Repaired Tetralogy of Fallot: A Marker for Liver and Heart?

Background and AimsPatients with repaired tetralogy of Fallot may develop chronic right ventricular dysfunction and hepatic congestion over time. We hypothesized that bile acid metabolism is altered in repaired tetralogy of Fallot patients and therefore sought to correlate right ventricular indices with serum bile acid levels.MethodsIndexed right ventricular end diastolic volume, as assessed by cardiac magnetic-resonance imaging, was classified as <100ml/m2 (Group 1, n = 5), 100–150ml/m2 (Group 2, n = 18), and >150ml/m2 (Group 3, n = 6) in 29 patients with repaired tetralogy of Fallot. Pulmonary regurgitation fraction and right ventricular ejection fraction were calculated. The serum bile acid profile, including 15 species, in these patients was determined by liquid chromatography coupled with mass spectrometry.ResultsSerum bile acid levels increased from Group 1 to Group 3 (2.5 ± 0.7; 4.1 ± 2.5; 6.0 ± 2.8 μmol/l, respectively) with significantly increased bile acid values in Group 3 compared to Group 1 (p≤0.05). In Group 3, but not in Group 1 and 2, a significant increase in glycine-conjugated bile acids was observed. Pulmonary regurgitation fraction increased (12 ± 1; 28 ± 16; 43 ± 3%, Groups 1–3, respectively) and right ventricular ejection fraction decreased (48.4 ± 6.4; 48.5 ± 6.5; 42.1 ± 5.3%, Groups 1–3, respectively) with rising indexed right ventricular end diastolic volume.ConclusionsThese preliminary results suggest that serum bile acid levels are positively correlated with indexed right ventricular end-diastolic volume in patients with repaired tetralogy of Fallot; however, this needs to be confirmed in a larger patient cohort.