Summary
Background
Pulmonary regurgitation (PR) is a common complication of right ventricular outflow tract (RVOT) reconstruction and leads to right ventricular (RV) dilatation and dysfunction. Although cardiac magnetic resonance (CMR) is the gold standard for evaluating PR and RV dysfunction, cost and limited availability are problems in many centres.
Aims
To determine clinical, electrocardiographic and echocardiographic predictors of these complications and optimize patient selection for their short-term follow-up by CMR.
Methods
Ninety-four patients with a history of RVOT repair were prospectively included. All patients had a clinical examination, electrocardiography, echocardiography and CMR.
Results
QRS duration, indexed end-diastolic RV (EDRV) diameter and area on echocardiography were significantly associated with RV dilatation on CMR ( P < 0.001). The distal localization of Doppler PR flow was the strongest echocardiographic criterion associated with severe PR ( P < 0.001). Arrhythmia history and high Tei index were significantly associated with low RV ejection fraction ( P < 0.001 and P = 0.017, respectively). In multivariable analysis, grade of PR, QRS duration, arrhythmia and valvulotomy were strongly associated with severe PR and RV dilatation or systolic RV dysfunction. From these results, an approach based on a scaled scoring system for selecting patients who need short-term CMR evaluation and close follow-up was evaluated. This method should avoid 31% of CMR examinations, with a sensitivity of 97.7%.
Conclusion
Clinical, electrocardiographic and echocardiographic criteria can be used to accurately evaluate patients with RVOT repair. The combination of such features facilitates identification of patients who do or do not require close CMR evaluation.
Résumé
Contexte
L’insuffisance pulmonaire (IP) est une complication fréquente de la reconstruction de la voie droite et entraîne une dilatation et une dysfonction du ventricule droit (VD). Bien que l’imagerie par résonance cardiaque soit la référence pour évaluer l’IP et la fonction VD, son coût et sa disponibilité limitée sont problématiques dans de nombreux centres.
Objectifs
Déterminer les critères cliniques, ECG et échocardiographiques prédictifs de ces complications et optimiser la sélection des patients pour un suivi à court terme de ces complications par IRM.
Méthodes
Quatre-vingt-quatorze patients ayant des antécédents de reconstruction de la voie droite ont été inclus prospectivement. Tous les patients avaient un examen clinique, un ECG, une échocardiographie et une IRM.
Résultats
La durée du QRS, le diamètre et la surface télédiastoliques indexés du VD en échocardiographie étaient significativement associés à une dilatation VD en IRM ( p < 0,001). La localisation distale de l’IP au Doppler était le critère le plus fortement corrélé à une IP sévère diagnostiquée en IRM ( p < 0,001). Les antécédents d’arythmies et un indice de Tei augmenté étaient significativement associés à une dysfonction VD ( p < 0,001 et p = 0,017, respectivement). En analyse multivariée, le grade de l’IP, la durée du QRS, l’arythmie et une valvulotomie étaient fortement associés à une IP sévère et une dilatation VD importante ou à une dysfonction systolique VD. À partir de ces résultats, une approche, basée sur un système de scores, pour sélectionner les patients qui ont besoin à court terme d’une évaluation IRM a été évaluée. Cette méthode permettrait d’éviter 31 % des examens IRM, avec une sensibilité de 97,7 %.
Conclusion
Des critères clinique, ECG et échocardiographiques peuvent être utilisés pour évaluer avec précision les patients ayant une chirurgie de la voie droite. La combinaison de ces caractéristiques permet de déterminer les patients qui nécessitent ou pas une évaluation rapprochée en IRM.
Introduction
Pulmonary regurgitation (PR) is a common complication of right ventricular outflow tract (RVOT) reconstruction and subsequent remodelling. Untreated severe PR may lead to irreversible right ventricular (RV) dilation and dysfunction. When timely pulmonary valve replacement (PVR) is performed, there is most often a reduction in RV size and an improvement in RV ejection fraction (RVEF). In contrast, when PVR is performed late, RV recovery is incomplete . Therefore, reasonably accurate quantification of the degree of PR and RV size and function is important in the management and follow-up of these patients.
Cardiac magnetic resonance (CMR), an accurate non-invasive imaging modality, has become the gold standard for the evaluation of patients with RVOT reconstruction and is now required for screening patients who require PVR . However CMR is time consuming and can be costly in a strategy requiring close CMR follow-up in all patients after RVOT reconstruction. Echocardiography is more widely available and allows an assessment of PR and RV size and function, although the limitations of ultrasound-based methods are well known. Few studies have compared echocardiography with CMR for the evaluation of RV volumes and function or the degree of PR in the tetralogy of Fallot (ToF) population. Most often, quantitative criteria are tested separately.
According to the recent European Society of Cardiology recommendations , all patients with RVOT reconstruction should have an annual cardiac follow-up to look for complications, and echocardiography should be performed as part of each visit. All patients should have further CMR during the first visit to a specialized Grown Up Congenital Heart centre. But the necessity and intervals for repeat CMR are not precisely discussed when no complication is found by clinical and echocardiography evaluation. There are no studies defining subgroups of patients at high risk of complications, who justifying close CMR follow-up.
Thus, we aimed to test the clinical, electrocardiographic (ECG) and echocardiographic criteria and to combine variables readily available in a simple score that would better define patients with a high risk of complications, to define a tailored screening strategy and determine the optimal use of CMR in the follow-up after RVOT reconstruction.
Methods
Study population
We prospectively included 94 patients (48 women and 46 men) from January 2008 to December 2010, following ethics approval and informed consent. The main inclusion criterion was a history of surgical reconstruction of RVOT ( Table 1 ). However, patients who underwent pulmonary valve implantation were excluded, as were patients with a pacemaker or defibrillator. All patients had a clinical examination, electrocardiography (ECG), echocardiography and CMR. Echocardiography and CMR were performed blind on the same day by two different operators (M.L. and E.M.) within a 6-hour period.
| Characteristics | |
|---|---|
| Men | 46 (48.9) |
| Age at inclusion (years) | 25 (21–34) |
| Heart disease | |
| Tetralogy of Fallot | 65 (69.1) |
| Pulmonary stenosis | 12 (12.8) |
| Double outlet right ventricle | 5 (5.4) |
| Absent pulmonary valve + VSD | 4 (4.2) |
| Pulmonary atresia | 4 (4.2) |
| Pulmonary atresia + VSD | 3 (3.2) |
| Truncus | 1 (1.1) |
| Age of RVOT repair (years) | 2 (1–6) |
| Time since surgery (years) | 23 (19–29) |
| Transannular patch | 61 (64.8) |
| Valvulotomy | 27 (28.7) |
| Unvalved conduit | 5 (5.3) |
Echocardiographic measurements
Echocardiographic examinations were performed in all patients with a Vivid 7 device (GE Medical Systems, Horten, Norway) ( Fig. 1 ). All studies were stored digitally and were available for offline analysis with Echopac software (GE Healthcare, Waukesha, WI, USA). RV diameters were measured from the parasternal long-axis view. End-diastolic RV (EDRV) and end-systolic RV (ESRV) areas were measured from the apical four-chamber view. RV diameters and areas were indexed to body surface area. The RV shortening fraction was calculated by the following formula: (EDRV area − ESRV area)/EDRV area. PR was assessed by pressure half time (PHT) and regurgitation index was calculated by the ratio of PR duration over diastole duration, measured from the pulmonary outflow by Doppler in the parasternal short-axis view, with continuous-wave sampling through the pulmonary annulus. The pulmonary diastolic retrograde flow was also detected between the pulmonary annulus and distal pulmonary arteries with the pulsed-wave sample volume, in the parasternal short-axis view. PR was classified as grade 1 (minimal) in the presence of a retrograde flow from the pulmonary annulus, grade 2 (moderate) in the presence of a retrograde flow from the pulmonary artery trunk and grade 3 (severe) if the retrograde flow was detected from distal pulmonary arteries. Localization of diastolic retrograde flow for PR quantification echocardiography has been already validated with CMR measurements . PR velocity was 0–2.5 m/s. Colour-coded myocardial velocities of the tricuspid annulus were acquired with a mean frame rate of 147 ± 21 frames/s. Isovolumic acceleration (IVA), a relatively load-independent variable, was measured at the lateral tricuspid annulus, as described by Vogel et al. . The peak of the systolic wave (S wave), which has been demonstrated to correlate with ejection fraction (EF) , was measured with tissue Doppler imaging (TDI) from the lateral tricuspid annulus. The Tei index was calculated as previously described , with tissue Doppler recordings from the lateral tricuspid annulus. Three consecutive cardiac cycles were averaged to correct for heart rate variation and measurement errors for all quantitative variables. Tricuspid regurgitation (TR) was diagnosed with colour flow imaging. When more than a small central TR jet was observed, the severity of TR was graduated according European recommendations , using vena contracta width, the flow convergence method and pulsed Doppler evaluation of hepatic vein flow. Most patients had mild TR (87/94), six had moderate TR and one had severe TR.
CMR measurements
CMR studies were performed on a 1.5-T system (Signa Hdx; GE Healthcare, Milwaukee, WI, USA). Using retrospective ECG-gated steady-state free-precession cine images, left ventricular (LV) and RV function were assessed by using successive breath-hold acquisitions in the axial view from the apex of the heart to the aortic arch, in six to nine two-chamber views to cover both ventricles and in a short-axis contiguous stack from the atrioventricular ring to the apex. Two to three slice levels were acquired during a single breath hold. The cine sequence variables were: repetition time 2.8 ms; echo time 1.4 ms; flip angle 45°; slice thickness 8 mm; matrix 320 × 192; field of view 380–300 mm; and temporal resolution 20 ms, by using 25–60 cardiac phases throughout the cardiac cycle. Assessment of RV volumes was performed by manually defining the endocardial outline at end-diastole and end-systole in each short-axis slice, using QMass Analysis software (MEDIS Medical Imaging Systems, Leiden, The Netherlands). RV trabeculae were excluded from the RV volumes. End-diastolic and end-systolic volumes were calculated using Simpson’s rule for each ventricle and, from these, the stroke volume and EF were calculated. RV volumes were indexed to body surface area. Two orthogonal long-axis views of the RVOT were then acquired for positioning of through-plane flow quantification at the midpoint of the pulmonary trunk. The phase contrast CMR sequence was performed with retrospective ECG gating, breath holding and the following variables: repetition time 7.3 ms, echo time 2–3 ms, two views per segment in order to obtain after view sharing a temporal resolution of 15 ms and 30–70 cardiac phases depending on the heart rate; 256 × 128 matrix interpolated to 256 × 256 in raw data with a 50% rectangular field of view of 300–330 mm. The velocity encoding value (VENC) was set initially at 150 cm/s and adjusted if aliasing artefacts occurred. In case of aliasing, VENC could be increased to 300 or 400 cm/s. After using semiautomated vessel edge detection, velocity was estimated in each pixel of the pulmonary artery section to measure instantaneous flow in mL/s, further integrated throughout the cardiac cycle, to calculate anterograde and retrograde volume in mL. The PR fraction was estimated by calculating the percentage of backward flow volume to forward flow volume.
Statistical analysis
In our study, severe PR was defined as CMR PR fraction ≥ 50%. RV dilatation was considered important when CMR EDRV volume was ≥ 150 mL/m 2 , according to the results of surgical PVR studies . According to the normal RVEF values measured on acquisitions with steady-state free precession , RVEF impairment was defined as CMR RVEF < 50%. The main outcomes were the presence of severe PR, important RV dilatation and RVEF impairment. Patients with RVOT repair complications were defined as patients with severe PR associated with important RV dilatation and/or RVEF impairment.
Univariate analyses (with the Wilcoxon test, Fisher’s exact test, the Chi-square test or the Chi-squared test for trends, as appropriate) and logistic regression analyses were used to identify clinical and echocardiographic variables associated with the outcomes. The final models were obtained using a backward selection, where predictive factors were the clinically relevant variables and echocardiographic factors that had a P value < 0.20 in the univariate test. Clinically relevant variables for each outcome were also studied. Linearity on the scale was checked for quantitative variables. Multicolinearity problems were assessed using correlation matrices.
The repeatability (intraobserver variability) and reproducibility (interobserver variability) of the echocardiographic assessments for quantitative variables (EDRV area, ESRV area, RV diameters, Tei index) were observed on Bland-Altman plots and analysed using intraclass correlation coefficients. All variables (except the Tei index) were log transformed to satisfy the normal distribution assumption. For the interobserver study, the mean of the two measures by the first observer was used. The assessment of the PR grade was analysed with kappa coefficients.
To select patients requiring close CMR monitoring, we used a scaled score to estimate the risk of RVOT repair complication. To obtain the most stable model, we performed a bootstrap resampling with 1000 replications and analysed the variables and combinations of variables selected from the 1000 multivariable logistic regression models with backward selection. The choice of the risk factors in the final model was based on the frequency of selection of factors and combination of factors. Once this step was achieved, we performed another 1000 logistic regressions including these factors in order to estimate the regression coefficients of the final model. The scores associated with quantitative factors were determined using four meaningful categories defined with the help of quartiles. Finally, we presented for each total score the risk of RVOT repair complication for the patient and the sensitivity, specificity and likelihood ratios of the score computed on the original sample.
SAS statistical software (version 9.1; SAS Institute Inc., Cary, NC, USA) was used for all analyses.
Results
Study population
Patient characteristics are listed in Table 1 . The majority of patients were asymptomatic (69.1% New York Heart Association class I). Seven patients (7%) had signs of right-sided congestive heart failure. All patients were in sinus rhythm during their examination. Electrocardiography showed complete right bundle branch block in 82% of patients. The median QRS duration was 150 ms. Nineteen patients (20%) had QRS ≥ 180 ms; 26% (24/94) had a history of arrhythmia; 22/94 had supraventricular tachycardia; and 2/94 had non-sustained ventricular tachycardia.
Correlates of severe RV dilatation, severe PR and RVEF impairment
Criteria for severe PR
We identified 53 patients (56%) with severe PR using CMR. The univariate analysis showed that younger age at RVOT repair, use of valvulotomy, QRS duration and echo-derived high grade of PR were significantly associated with severe PR in CMR (PR ≥ 50%). The other echocardiographic criteria were not correlated with PR severity. In multivariable analysis, valvulotomy and echo-derived grade of PR remained significant ( P < 0.001) correlates of severe PR. A patient with an echo-derived PR graded 3 was almost 50 times more likely to have severe PR in CMR (odds ratio [OR] = 47.8, 95% confidence interval [CI] 11.4–198.8; P < 0.001). The risk of severe PR increased about five times for a patient with a history of valvulotomy (OR 5.4, 95% CI 1.4–19.9; P = 0.012).
Correlates of RV dilatation
Thirty-five out of 94 (37%) patients had important RV dilatation according to CMR ( Table 2 ). The univariate analysis showed that ToF, presence of a transannular patch, QRS duration, indexed RV diameters and indexed EDRV and ESRV areas were significantly associated with RV dilatation in CMR (EDRV volume ≥ 150 mL/m 2 ). After backward selection in multivariable logistic regression, QRS duration, indexed EDRV diameter and indexed EDRV area in echocardiography remained significantly associated with RV dilatation in CMR ( P < 0.001). Patients with the largest QRS, indexed EDRV diameter and/or indexed EDRV area were more likely to have RV dilatation. For an increase of 5 mm/m 2 in indexed EDRV diameter, the risk of important RV dilatation increased more than two times (OR 2.2, 95% CI 1.2–3.9; P = 0.007). The OR for an increase of 5 cm 2 /m 2 in indexed EDRV area was 1.6 (95% CI 1.1–2.4; P = 0.010) and an increase of 10 ms in QRS resulted in a 1.3 times increase in the risk of having important RV dilatation (OR 1.3, 95% CI 1.03–1.6; P = 0.021).
