The aim of this study was to determine if adult patients with repaired tetralogy of Fallot are being referred for pulmonary valve replacement (PVR) earlier on the basis of cardiac magnetic resonance imaging (CMR) parameters despite the absence of CMR-based recommendations in the American College of Cardiology and American Heart Association joint guidelines. Variables defined by the guidelines were analyzed in conjunction with CMR-based parameters across 3 groups defined by the release of the guidelines: (1) patients referred before the guidelines, (2) patients referred 0 to 3 years after the guidelines, and (3) patients referred ≥3 years after the guidelines. Seventy-nine patients were identified. No significant trend was observed in guideline-defined variables. Significant trends in indexed right ventricular end-diastolic volume (p = 0.034), indexed right ventricular end-systolic volume (p = 0.001), and the right ventricular ejection fraction (p = 0.005) were observed across groups. By multivariate regression, patients who underwent PVR ≥3 years after the release of the guidelines had a 29 ml/m 2 smaller indexed right ventricular end-diastolic volume (p = 0.01) and a 33 ml/m 2 smaller indexed right ventricular end-systolic volume (p <0.001) compared with patients who underwent PVR before the release of the guidelines. PVR 0 to 3 years after the guidelines was not a significant predictor of either indexed right ventricular end-diastolic volume (p = 0.93) or indexed right ventricular end-systolic volume (p = 0.18). Patients referred for PVR ≥3 years after the guidelines had significantly smaller CMR-based right ventricular volumes without significant trends in guideline-defined variables. Given the increased use of CMR to guide PVR referral, revisiting the guidelines to address appropriate use of CMR derived thresholds is indicated.
Highlights
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There is no discussion of when to use CMR to guide referral for PVR in patients with tetralogy of Fallot in the guidelines.
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In our study, patients were referred for PVR earlier with smaller right ventricular volumes by CMR.
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We found no change in non-CMR-based patient characteristics over time.
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Patients are likely being referred for PVR earlier secondary to CMR-based volumes.
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The ACC/AHA guidelines should be modified to guide the proper use of CMR in this population.
Severe pulmonary regurgitation (PR) in adults with repaired tetralogy of Fallot (rTOF) plays an important role in patient outcomes and can lead to adverse sequelae, such as right ventricular dilation and biventricular dysfunction. Although pulmonary valve replacement (PVR) can be effective in reversing aberrant remodeling, uncertainty exists regarding the optimal timing of PVR. The American College of Cardiology (ACC) and American Heart Association (AHA) released joint guidelines in 2008 to aid decision making for PVR referral. These guidelines provided qualitative recommendations for PVR without specifying quantitatively what these constitute. In contrast, cardiac magnetic resonance imaging (CMR)–based volumetric thresholds for referral for PVR have been suggested in a series of studies published from 2000 to 2012. Increasing variability in referral patterns for PVR have been observed, and asymmetric adoption of CMR-based thresholds may be partially responsible. The aim of this study was to determine if adult patients with rTOF are being referred for PVR earlier on the basis of CMR parameters despite the absence of CMR-based recommendations in the ACC/AHA guidelines.
Methods
We conducted a retrospective, cohort study evaluating all patients aged ≥18 years with rTOF at the Schneeweiss Adult Congenital Heart Center at Columbia University who underwent PVR from January 1, 1999, to February 2, 2014. Patients followed long term at our center and those referred for a single visit before PVR were included. We divided patients into 3 groups to evaluate for temporal changes in clinical practice after the release of the guidelines on December 2, 2008. Group 1 included patients who underwent PVR before the release of the guidelines. Group 2 included patients who underwent PVR patients within 3 years of the release of the guidelines (December 2, 2008, to December 2, 2011). Group 3 included all patients who underwent PVR ≥3 years after the release of the guidelines (December 3, 2011, to February 2, 2014). A predetermined set of clinical variables and imaging characteristics based on previous studies and the ACC/AHA guidelines were defined before data acquisition, as described below.
Clinical and demographic variables were determined via review of written and electronic medical records. Details and timing of each patient’s initial surgical repair and any subsequent procedure, including PVR, were recorded.
Patients were considered symptomatic if they reported dyspnea, decreased exercise tolerance, or exertional chest pain before PVR. The presence of clinically significant arrhythmias was defined as sustained, nonsinus supraventricular tachycardia or sustained ventricular tachycardia documented on 12-lead electrocardiography, Holter monitoring, or electrophysiology. Right ventricular outflow tract obstruction was defined as a gradient ≥50 mm Hg by preoperative cardiac catheterization.
We reviewed reports from preoperative 2-dimensional color Doppler transthoracic echocardiograms for each patient. All studies were performed and interpreted at the Schneeweiss Adult Congenital Heart Center by cardiologists with years of expertise in congenital cardiac echocardiography. The severity of PR and tricuspid regurgitation was graded visually. Patients were classified as having mild or less tricuspid regurgitation or moderate or greater tricuspid regurgitation by transthoracic echocardiography. Right ventricular function was assessed and defined as normal or abnormal (including mild, moderate, and severe dysfunction) on the basis of echocardiographic appearance.
CMR studies were performed with breath holding and electrocardiographic gating using a Signa 1.5-T magnetic resonance imaging scanner (GE Healthcare, Milwaukee, Wisconsin) and an 8-channel phased array. Before June 2003, short axis cine gradient echocardiographic images were obtained with the following parameters: repetition time 8.8 ms, echo time 15.2 ms, flip angle 15°, 8 views per segment, field of view 30 cm, acquisition matrix 256 × 128, slice thickness 8 mm with no gap, and receiver bandwidth 31.25 kHz. From June 2003 onward, short-axis cine images were acquired using a steady-state free precession pulse sequence with the following parameters: repetition time 3.6 ms, echo time 11.5 ms, flip angle 45°, 24 views per segment, field of view 35 cm, acquisition matrix 192 × 160, slice thickness 8 mm with no gap, receiver bandwidth 125 kHz.
Images were reviewed and analyzed using ReportCARD software (GE Healthcare). A single reader with training and years of expertise in CMR imaging who was blinded to clinical status and the results of echocardiography performed CMR image analysis. Cine loops were used to select images at end-diastole and end-systole. End-diastole and end-systole were defined independently for the right and left ventricles as the phases with the largest and smallest volumes, respectively. Endocardial segmentation was performed by manual tracing of each end-diastolic and end-systolic short-axis view; areas were multiplied by slice thickness and summed to calculate right and left ventricular volumes. By convention, trabeculations and papillary muscles were considered part of the ventricular cavity in systole and diastole. Ejection fractions were calculated using the end-diastolic and end-systolic values.
Testing for a significant trend across groups was conducted using Goodman and Kruskal’s gamma statistic for categorical variables. For continuous variables, we used an extension of Wilcoxon’s rank-sum test developed by Cuzick to test for trend across groups. To assess between-group differences in CMR parameters of interest, including indexed right ventricular end-diastolic volume (RVEDVi), indexed right ventricular end-systolic volume (RVESVi), and the right ventricular ejection fraction (RVEF), we first constructed univariate linear regression models with individual predictors. On the basis of the univariate analysis, we constructed multivariate linear regression models. Age at PVR and moderate or greater tricuspid regurgitation were prespecified for inclusion in the model, and any additional covariates reaching p <0.20 in univariate analysis were included. For linear regression models, the time from release of guidelines variable was modeled as a categorical variable, with group 1 defined as the reference group. All statistical analyses were performed using Stata version 13.1 (StataCorp LP, College Station, Texas).
Results
Seventy-nine patients with rTOF underwent surgical PVR at our institution from February 18, 1999, to February 2, 2014. Every patient had moderate or greater PR. Thirty-six patients (46%) were in group 1, 24 patients (30%) were in group 2, and 19 patients (24%) were in group 3. Table 1 summarizes the demographic and preoperative characteristics of our patients. Table 2 summarizes the demographic and clinical characteristics of patients by timing of PVR. There was no significant trend in any demographic or clinical characteristic across groups ( Table 2 ).
| Variable | All Patients (n = 79) | CMR (n = 71) | No CMR (n = 8) |
|---|---|---|---|
| Male | 44 (56%) | 39 (55%) | 5 (63%) |
| Age at PVR, mean, (years) | 36 ± 1.2 | 35 ± 1.2 | 41 ± 5.1 |
| Pulmonary artery stenosis | 11 (14%) | 10 (14%) | 1 (13%) |
| Right sided arch | 6 (8%) | 6 (8%) | 0 |
| Atrial septal defect | 2 (3%) | 2 (3%) | 0 |
| Absent pulmonary valve | 1 (1%) | 1 (1%) | 0 |
| Coarctation of the aorta | 1 (1%) | 1 (1%) | 0 |
| Cor triatriatum | 1 (1%) | 1 (1%) | 0 |
| Anomalous coronary | 1 (1%) | 1 (1%) | 0 |
| Patent ductus arteriosus | 1 (1%) | 1 (1%) | 0 |
| Prior Procedures | |||
| Blalock-Taussig shunt | 26 (33%) | 26 (37%) | 0 |
| Pulmonary artery stent | 11 (14%) | 10 (14%) | 1 (13%) |
| PFO/ASD closure | 3 (4%) | 2 (3%) | 1 (13%) |
| Tricuspid valve repair | 3 (4%) | 3 (4%) | 0 |
| Maze | 2 (3%) | 2 (3%) | 0 |
| Additional VSD closure | 2 (3%) | 2 (3%) | 0 |
| Coarctation of the aorta repair | 1 (1%) | 1 (1%) | 0 |
| Ligation of patent ductus arteriosus | 1 (1%) | 1 (1%) | 0 |
| NYHA Class ≥2 | 23 (29%) | 21 (30%) | 2 (25%) |
| ≥Moderate Tricuspid Regurgitation | 11 (14%) | 9 (13%) | 2 (25%) |
| RV-PA Gradient >50 mm HG | 1 (1%) | 0 (0) | 1 (13%) |
| Symptoms | 36 (46%) | 31 (44%) | 5 (63%) |
| Peak VO 2 , median, (cc*kg/min) | 26.7 (9) | 26.7 (8) | 23.7 (11) |
| Time from PVR to CMR, median, (months) | 8.6 (15) | 8.6 (15) | — |
| Group 1 ∗ | Group 2 ∗ | Group 3 ∗ | p-value for trend | |
|---|---|---|---|---|
| Age at PVR, mean, (years) | 37 ± 1.7 | 35 ± 2.2 | 36 ± 2.6 | 0.73 |
| Echocardiographic data | ||||
| ≥Moderate TR | 6 (17%) | 2 (8%) | 3 (17%) | 0.29 |
| Elevated RVOT gradient | 4 (11%) | 1 (4%) | 1 (5%) | 0.36 |
| Decreased RV function | 22 (61%) | 6 (25%) | 7 (39%) | 0.17 |
| Symptoms | ||||
| Dyspnea | 10 (28%) | 12 (50%) | 5 (28%) | 0.18 |
| Chest Pain | 2 (6%) | 2 (8%) | 3 (17%) | 0.29 |
| Any Arrhythmia | 9 (25%) | 8 (33%) | 2 (11%) | 0.20 |
| Any Symptom | 12 (33%) | 12 (50%) | 12 (67%) | 0.16 |
| NYHA Class ≥2 | 14 (39%) | 8 (33%) | 1 (5%) | 0.17 |
| Peak VO 2 † , median (cc*kg/min) | 24.4 (10) | 26.3 (8) | 28.5 (6) | 0.09 |
∗ Group 1 represents patients referred before the guidelines, Group 2 represents patients referred 0–3 years after the release of the guidelines, and Group 3 represents patients released ≥3 years after the release of the guidelines.
Of the 79 patients with rTOF who underwent PVR, preoperative CMR data were available for 71 patients (90%). The remaining 8 patients who did not undergo preoperative CMR had pacemakers or implantable cardioverter-defibrillators. Ten outside hospital CMR studies were reviewed for accuracy but not overread, because of software incompatibility. The number of CMR studies reviewed but not overread did not differ significantly across groups (p = 0.30). Median time from CMR to PVR was 8.6 months and did not differ significantly between groups (p = 0.84). Box plots of RVEDVi, RVESVi, and RVEF by group are illustrated in Figures 1, 2 , and 3 . There were significant decreasing trends in RVEDVi (p = 0.034) and RVESVi (p = 0.001) and an increasing trend in RVEF (p = 0.005) across groups.
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