Sonya V. Babu-Narayan

Neurohormonal activation and its relation to outcomes late after repair of tetralogy of Fallot

Background Brain natriuretic peptide (BNP) levels are elevated in patients with repaired Tetralogy of Fallot (rTOF), the clinical significance of which remains uncertain. Methods and results Ninety consecutive adults (≥16 years) with rTOF (mean age 32.7±11.3 years, 64% men) were prospectively recruited from a single tertiary centre, together with 15 age-matched and gender-matched controls. Patients with rTOF had elevated BNP (8.9 (5.9–14.6) vs 5.4 (2.2–7.5) pmol/L; p<0.01), and BNP activation was common even in asymptomatic patients. Also, atrial natriuretic peptide (6.9 (4.0–9.9) vs 3.3 (1.0–4.0) pmol/L; p<0.01), endothelin-1 (1.14 (0.94–1.48) vs 0.75 (0.44–0.93) pmol/L; p<0.01) and renin (55.0 (45.5–66.5) vs 18.6 (12.0–22.7) pmol/L; p<0.01) were elevated at baseline compared with controls. Interactions between BNP with endothelin-1, cardiothoracic ratio and right atrial area were evident. Eight deaths occurred over a median follow-up of 10 years. On Cox regression analysis, BNP emerged as a strong predictor of death (HR 1.16 per 10 pmol/L, 95% CI 1.05 to 1.29; p<0.01). Survival receiver operating curve analysis revealed an optimum cut-off of BNP ≥15 pmol/L (=52 pg/mL), above which BNP was related to significantly increased mortality (HR 5.40, 95% CI 1.29 to 22.6; p<0.01); absolute mortality at 5 years 19% vs 3% in patients with BNP ≤15 pmol/L. BNP was also a predictor of sustained arrhythmia (HR 2.06 per 10 pmol/L, 95% CI 1.32 to 3.21; p<0.05). Conclusions Neurohormonal activation is present in adults with rTOF including asymptomatic patients. BNP level ≥15 pmol/L is associated with a fivefold increased risk of death. These data suggest that BNP measurement in patients with rTOF should be incorporated in the periodic risk stratification assessment of these patients under lifelong follow-up.

Quantifying right ventricular diffuse fibrosis in tetralogy of Fallot - a novel customised approach for the challenges of the right ventricle

NIHR Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, London, UK Full list of author information is available at the end of the article Figure 1 Representative short-axis images from subjects scanned for RV T1 mapping by fat-water separated, MSPrep dark blood imaging. Images for five subjects with repaired tetralogy of Fallot and five healthy volunteers shown (one subject per column): Top row MoCo averaged water-only image at Ts 600 ms, Second row MoCo averaged water-only anchor image at same window/level, Third row MoCo averaged fat only image, Bottom row T1 map generated from registration and 2-parameter fit of the six images per sampling scheme. Heng et al. Journal of Cardiovascular Magnetic Resonance 2016, 18(Suppl 1):O26 http://www.jcmr-online.com/content/18/S1/O26

YI-3 Early cardiac remodelling after pulmonary valve replacement in patients with repaired tetralogy of fallot

Background Whilst pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF) is shown to provide symptomatic benefit and reduction of right ventricular (RV) volumes, there are scarce data on the rate of ventricular mechanical and biological adaptation. We aimed to assess early and late post-PVR volumetric and functional changes. Methods and Results Patients with rTOF (≥16 years) for PVR were prospectively recruited for Cardiovascular Magnetic Resonance (CMR): pre-PVR (pPVR), early post-PVR at median 6 days (ePVR) and late post-PVR at median 3 years (mPVR). Fifty-seven patients with rTOF (mean age 35.8 ± 10.1 years, 38 male) were included. There was an acute reduction in indexed RV end-diastolic (EDVi), end-systolic (ESVi) volumes and mass early post-PVR, which was sustained at latest time point (RVEDVi pPVR 156.1 ± 41.9ml/m² vs ePVR 104.9 ± 28.4ml/m² vs mPVR 104.2 ± 34.4ml/m2 and RVESVi pPVR 74.9 ± 26.2ml/m² vs ePVR 57.4 ± 22.7ml/m² vs mPVR 50.5 ± 21.7ml/m2;p < 0.01). Seventy percent of patients achieved postoperative normal range diastolic and systolic RV volumes which were predicted by a preoperative RVEDVi≤158ml/m2and RVESVi≤82ml/m2. PVR produced a stepwise reduction in RVESVi (load independent variable) together with an improvement in corrected RVEF after restoring valve competency (which is load dependent). There was also a modest but significant improvement of LVEF, as well as reverse right atrial remodelling. Conclusions Cardiac remodelling is generally regarded as a gradual process post-PVR. We demonstrate for the first time that the major improvement in RV volumes seen at midterm follow-up have already taken place within days after surgery. This occurs with an apparent transient impairment of RVEF, although corrected RVEF more easily illustrates the immediate effect of PVR. However, RVESVi may be a more appropriate, load-independent marker that better reflects the early and sustained benefit of PVR on RV contractility.

Tailoring counselling after pulmonary valve surgery in repaired tetralogy of Fallot

The success of cardiac surgery over the past six decades has led to a paradigm shift in the management of patients with repaired tetralogy of Fallot (rTOF) towards addressing late sequelae in adulthood. Although surgical techniques have evolved, late morbidity and mortality have not been abolished in this patient cohort. Significant knowledge gaps remain in mediating adverse outcomes of arrhythmias, heart failure and sudden cardiac death. Surgical repair of TOF almost inevitably results in pulmonary regurgitation (PR) during the relief of RV outflow tract obstruction. While pulmonary valve replacement (PVR) represents the current standard of care for treating the haemodynamic consequences of pulmonary dysfunction, its survival benefit and impact on long-term morbidity remains largely unproven. Contemporary guidelines advocate PVR in the presence of symptoms, significant or progressive RV dilatation or dysfunction.1 However, decision-making favouring intervention is less straightforward in the asymptomatic cohort that forms the majority of patients with rTOF with significant PR. Irreversible ventricular impairment may ensue when intervening too late with chronic volume loading, while operating prematurely may increase the lifetime cumulative number of procedures and confer surgical risk, which may increase with successive sternotomies. Ascertaining the optimal timing of PVR therefore remains elusive. Outcomes in patients with rTOF following PVR are …

9 ECV and T1 mapping in repaired tetralogy of fallot – CMR diffuse fibrosis measurement needs the right method for the right ventricle?

Introduction It is increasingly appreciated applying parametric mapping to the RV has inherent challenges. Methods We studied native LV and RV T1 mapping and ECV measures at 1.5 T in repaired tetralogy of Fallot (rTOF) patients (n=44, 24 male, 32±14 years, 35 (80%), NYHA class I). Single slices targeted perpendicular to to the LV septum or RV inferior wall using 11HB-MOLLI (6 mm slice thickness/TR 279 ms/TE 1.1 ms/Flip-angle 35°). Like image planes were repeated using ‘high sensitivity native T1’ 14HB-MOLLI (6 mm slice thickness/TR 300 ms/TE 1.1 ms/Flip-angle 5°) in attempt to improve sensitivity to tissue collagen. Haematocrit for ECV calculation was obtained within a few hours of CMR. Results RVECV correlated with LVECV (r=0.7; p<0.001). Nineteen (46%) had increased RVECV (>35%) and 3 (8%) increased LVECV (>30%). Associations with all standard risk factors in rTOF were tested. RVECV correlated with right atrial area, (r=0.4; p<0.05). ‘High-sensitivity native T1’ correlated with akinetic RVOT length (r=0.6; p<0.05), and left atrial area (r=0.3; p=0.07) and QRS duration (r=0.3; p=0.4). RVECV did not correlate with high-sensitivity’ native T1. No diffuse RV fibrosis measure correlated with ejection fraction. Conclusion Diffuse fibrosis was only associated with increased right atrial and RVOT akinetic area size which if true may relate to RV diastolic dysfunction. Given the lack of consistency of findings between techniques more data are needed, including determination of how the measures obtained relate to myocardial composition. Despite best efforts to obtain optimum RV T1 maps these findings suggest current approaches have limited use and dedicated RV sequence development is required.

Pregnancy in Repaired Tetralogy of Fallot

Pregnancy in repaired tetralogy of Fallot may be associated with arrhythmia, heart failure and low birthweight babies. Women who have favourable anatomy and underwent uncomplicated repair of tetralogy of Fallot in childhood can expect low risks in pregnancy and good life expectancy. However, higher maternal risk is associated with features such as more complex underlying anatomy and surgical history, residual or postoperative haemodynamically significant lesions and abnormal right or left ventricular function. For selected patients, prepregnancy intervention for the most common lesion, pulmonary regurgitation, may be justified. For women without a family history of congenital heart disease, the risk of vertical transmission is low at around 2-3% unless the patient also has DiGeorge syndrome which will affect 50% of offspring. Elective DiGeorge genetic testing should be offered at precounselling and fetal echocardiography in the antenatal period.

Consideration for Automatic Implantable Cardioverter-Defibrillator in Tetralogy

At the age of 6 years, this patient had a Brock procedure (1958). Using a transpulmonary approach, Lord Brock resected subpulmonary muscle to relieve the pulmonary stenosis, leaving the patient’s VSD untouched. Three years later, at the age of 9 years, he presented with further cyanosis and fainting, and underwent tetralogy repair, also by Lord Brock. The operative note described the following: “Bicuspid pulmonary valve—stretched with an expanding dilator,” “the fibro-endocardial tissue constituting the infundibular stenosis was carved away liberally,” “the VSD was closed with a pericardial patch.” The postoperative notes document a pulmonary diastolic murmur. A year later the patient experienced an episode of VT requiring DC cardioversion at a local hospital. Again, at age 14 years, he had a further episode of sustained VT, which apparently occurred following a blow to the chest. This resolved spontaneously. The patient felt well and had no further workup or adverse event. There was no routine cardiac follow-up until the patient was 44 years old. At that time he complained of palpitations. Although each episode was short lived, he had noted these several times over the previous 9 years. On reassessment he was found to have moderate to severe PR by echocardiography. Both sustained VT and nonsustained VT were also documented on 24-hour Holter ECGs over the following 5 years. At age 50 his exercise capacity was normal, and his only complaint was of occasional palpitations. His PR was reevaluated, and found to be severe by echocardiography and cardiac catheterization. He had normal coronary arteriograms. Because the patient was “asymptomatic” with above-average exercise tolerance, a decision was made to defer PVR, and that there was no current indication for electrophysiologic ablation. Medication for arrhythmia was declined by the patient who felt that this might treat only the palpitations rather than the underlying cause. In the years that followed, palpitations were described as either single beats, or short-lived regular and fast heart rhythms relieved by a Valsalva maneuver. His exercise tolerance remained very good. V1