Patients with tetralogy of Fallot (TOF) after complete repair and pulmonic stenosis (PS) after surgical valvotomy often develop significant pulmonic regurgitation (PR) that eventually requires valve replacement. Although criteria exist for the timing of pulmonary valve replacement in TOF, it remains less clear when to intervene in valvotomy patients and whether TOF recommendations can be applied. Our aim was to compare the structural and functional sequelae of valvotomy for PS with complete repair for TOF. We compared the clinical characteristics, electrocardiograms, echocardiograms, cardiac magnetic resonance imaging (MRI), and invasive hemodynamics of 109 adults (34 PS and 75 TOF) newly referred to a congenital heart disease center for evaluation of PR between 2005 and 2012. Both cohorts were similar in terms of baseline demographics and presenting New York Heart Association function class. Valvotomy patients had a slightly greater degree of PR by echocardiogram, although it was similar by cardiac MRI. Electrocardiography QRS width was greater in patients with TOF (114 ± 27 vs 150 ± 28 ms, p <0.001). MRI right ventricular ejection fraction (49 ± 8 vs 41 ± 11%, p = 0.001) and left ventricular ejection fraction (59 ± 7 vs 52 ± 10%, p = 0.002) were lower in patients with TOF. Pacemaker or defibrillator implantation was significantly greater in patients with TOF (3% vs 23%, p = 0.011). In conclusion, patients postvalvotomy and complete repair present with similar degrees of PR and severity of symptoms. Biventricular systolic function and electrocardiography QRS width appear less affected, suggesting morphologic changes in TOF and its repair that extend beyond the effects of PR. These findings suggest the need for developing disease-specific guidelines for patients with PR postvalvotomy.
Tetralogy of Fallot (TOF) and isolated pulmonic stenosis (PS) are common congenital disorders that often require early corrective intervention. Traditional corrective surgery for TOF (“complete repair”) and surgical valvotomy for PS frequently have resulted in significant pulmonic regurgitation (PR). In both populations, the resultant PR places patients at risk for right ventricular (RV) dysfunction, arrhythmias, and sudden death. Pulmonary valve replacement (PVR) is the gold standard therapeutic option because medical management is often ineffective. The timing of PVR is controversial, with early replacement limited by long-term prosthetic valve degeneration and delayed replacement risking the development of irreversible RV damage. For this reason, the timing of PVR after TOF repair has been well-studied, and specific guidelines exist to determine the appropriate timing of intervention. Unfortunately, few studies exist to guide the timing of PVR in the PS population. Many providers, therefore, apply the TOF guidelines to valvotomy patients despite the fundamentally different anatomy, pathophysiology, and surgical corrections of these conditions. To assess whether the two populations are truly comparable, we examined the structural, functional, and symptomatic sequelae of patients with PR resulting from TOF repair and valvotomy referred for initial assessment at an adult congenital heart disease center.
Methods
In this retrospective, incipient cohort study, we identified 109 patients from the Cleveland Clinic Adult Congenital Heart Disease Database who were newly referred between July 2005 and June 2012 for evaluation of moderate or greater native valve PR (as quantified by echocardiography) related to previous surgical repair of PS or TOF. All patients underwent an electrocardiogram and an echocardiogram at the initial clinic visit, with cardiac magnetic resonance imaging (MRI) and heart catheterization subsequently performed in appropriately selected patients. Patients with left bundle branch block, previous PVR, or those with greater mild RV outflow narrowing evident on imaging were excluded. In addition, those with other major additional cardiac malformations (i.e., double-chambered right ventricle, transposition of great vessels, atrioventricular canal type defect or anomalous pulmonary venous return) were excluded. Other cardiac comorbidities, including residual atrial and ventricular septal defects and peripheral pulmonic stenosis, were individually reviewed by a committee of investigators for their contribution to cardiac structure and risk of arrhythmia before possible exclusion. The study was approved by the Institutional Review Board of the Cleveland Clinic.
Data were abstracted from the database and augmented by review of the electronic and paper medical records, which included baseline demographics, cardiac medical and surgical history, comorbidities, symptom severity as measured by New York Heart Association functional class, electrocardiographic and imaging data, and hemodynamic tracings.
Electrocardiogram analysis was limited to nonpaced tracings. Blinded, qualitative assessments of cardiac chamber sizes by echocardiography were quantified as: 0 = normal, 1 = mild, 2 = moderate, 3 = moderate to severe, and 4 = severe enlargement. Similarly, RV function by echocardiogram was quantified as: 0 = normal, 1 = mild, 2 = moderate, 3 = moderate to severe, and 4 = severe dysfunction. Cardiac catheterization data included right heart pressures, cardiac index calculated by Fick method, and the presence and severity of coronary artery disease. Cardiac MRI data included chamber sizes and function, quantified valvular regurgitation, and aortic dimensions. Volumetric data by MRI was indexed using body surface area.
Comparisons of dichotomous variables between groups were performed using the Pearson chi-square test, Fisher’s exact test, or Wilcoxon rank-sum test where appropriate. Comparisons of continuous variables were performed using two-sided t-tests. For all tests, a p <0.05 was considered statistically significant. Data analyses were performed using JMP Pro software version 9.0.0 (SAS Institute Inc., Cary, North Carolina).
Results
A total of 109 patients (34 PS valvotomy and 75 TOF complete repair) were included in the final analysis ( Table 1 ). Basic demographic data, including age, gender, and body mass index, were similar between groups. There was no difference in mean age at corrective surgery. Patients with PS presented to the Adult Congenital Heart Disease Center an average of 37.5 ± 10.5 years after surgery compared with 32.3 ± 10.6 years in patients with TOF (p = 0.023). Not surprisingly, because of anatomic limitations, patients with repaired TOF were significantly more likely to have required palliative shunting and eventual placement of a pacemaker or cardiac defibrillator. Cardiovascular and noncardiovascular comorbidities were otherwise similar. At presentation, the PS group reported a greater prevalence of chest pain (29% vs 12%, p = 0.026) and shortness of breath at rest (32% vs 15%, p = 0.033). All other symptoms—including fatigue, cyanosis, orthopnea, palpitations, dyspnea on exertion, home oxygen supplementation and edema—were similar in prevalence between the two groups. Severity of symptoms at presentation also was similar as determined by New York Heart Association function class. Complete operative records were available for 23% of the cohort. Of the TOF subset, 33% of the repairs included known use of a transannular patch.
| Variable | Pulmonic Stenosis (n = 34) | Tetralogy of Fallot (n = 75) | p Value |
|---|---|---|---|
| Age, years | 47.0 ± 13.5 | 43.9 ± 13.3 | 0.260 |
| Male | 17 (50%) | 43 (58%) | 0.536 |
| Body mass index, kg/m 2 | 28.6 ± 7.1 | 27.4 ± 6.8 | 0.388 |
| Age at first repair, years | 6.8 ± 8.5 | 8.5 ± 10.3 | 0.411 |
| Time from repair to presentation, years | 37.5 ± 10.5 | 32.3 ± 10.6 | 0.023 |
| Shunt | 1 (3%) | 30 (40%) | <0.001 |
| Pacer/implantable cardiac defibrillator | 1 (3%) | 17 (23%) | 0.011 |
| New York heart Association functional class | 1.7 ± 0.7 | 1.6 ± 0.6 | 0.506 |
| Hypertension | 11 (32%) | 19 (25%) | 0.491 |
| Pulmonary hypertension | 1 (3%) | 11 (15%) | 0.100 |
| Diabetes mellitus | 2 (6%) | 4 (5%) | 1.000 |
| Hyperlipidemia | 3 (9%) | 12 (16%) | 0.383 |
| Smoker | 8 (24%) | 18 (24%) | 1.000 |
Nonpaced electrocardiographic data were obtained from 95 patients (31 valvotomy and 64 complete repair). PR and corrected QT intervals were similar in both groups ( Table 2 ). QRS duration, however, was significantly greater in the TOF group.
| Variable | Pulmonic Stenosis | Tetralogy of Fallot | p Value |
|---|---|---|---|
| PR interval, ms | 177 ± 32 | 177 ± 55 | 0.946 |
| QRS width, ms | 114 ± 27 | 150 ± 28 | <0.001 |
| QTc, ms | 421 ± 51 | 420 ± 53 | 0.888 |
| Right atrium volume, ml | 25.1 ± 10.6 | 27.0 ± 10.6 | 0.560 |
| Right ventricle volume † | 1.5 ± 1.0 | 1.5 ± 1.0 | 0.761 |
| Right ventricle function ∗ † | 1 (0,2) | 1 (0,2) | 0.512 |
| Left ventricle diastolic width, cm | 4.4 ± 0.5 | 4.5 ± 0.8 | 0.457 |
| Left ventricle systolic width, cm | 2.9 ± 0.5 | 3.1 ± 0.6 | 0.289 |
| Left ventricle function ∗ † | 0 (0,0) | 0 (0,0) | 0.163 |
| Aortic regurgitation ∗ ‡ | 0 (0,0) | 0.5 (0,2) | 0.021 |
| Pulmonic regurgitation ‡ | 3.2 ± 0.9 | 2.4 ± 1.6 | 0.004 |
| Mitral regurgitation ‡ | 0.9 ± 0.6 | 0.9 ± 0.9 | 0.869 |
| Tricuspid regurgitation ‡ | 1.5 ± 1.0 | 1.5 ± 0.9 | 0.853 |
| Pulmonic gradient, mm Hg | 8.2 ± 3.1 | 13.9 ± 8.2 | 0.007 |
| Right ventricular systolic pressure, mm Hg | 35 ± 13 | 46 ± 20 | 0.007 |
| Left ventricle ejection fraction, % | 56 ± 5 | 54 ± 8 | 0.166 |
∗ Data given as median (IQ range).
† Volume/function graded from 0 (normal) to 3 (severely dilated/decreased).
‡ Valvular regurgitation graded as 0 (none), 1 (mild) to 4 (severe).
Echocardiographically assessed RV size (mildly to moderately enlarged) and function (mildly decreased) was similar in the 2 groups ( Table 2 ). PR, assessed qualitatively, was slightly more severe in the postvalvotomy group, whereas aortic regurgitation was worse in TOF. RV systolic pressure and pulmonic outflow gradient were both slightly greater in the TOF cohort.
Complete cardiac catheterization data were available in 56 patients (18 PS and 38 TOF). These data demonstrated similar hemodynamics, including right atrial pressure, pulmonary artery pressure, and cardiac indexes in both groups ( Table 3 ).
| Variable | Pulmonic Stenosis (n = 18) | Tetralogy of Fallot (n = 38) | p Value |
|---|---|---|---|
| Right atrial mean, mm Hg | 10.1 ± 5.4 | 11.4 ± 6.5 | 0.487 |
| Systolic pulmonary artery, mm Hg | 35.4 ± 11.6 | 42.2 ± 22.2 | 0.159 |
| Diastolic pulmonary artery, mm Hg | 12.6 ± 5.1 | 13.8 ± 10.5 | 0.584 |
| Mean pulmonary artery, mm Hg | 21.0 ± 5.2 | 23.9 ± 14.2 | 0.348 |
| Systolic right ventricle, mm Hg | 41.2 ± 12.9 | 50.3 ± 20.5 | 0.102 |
| Diastolic right ventricle, ∗ mm Hg | 10 (5, 14) | 10 (6, 13.5) | 0.767 |
| Mean pulmonary capillary wedge pressure, mm Hg | 12.5 ± 4.9 | 13.0 ± 5.4 | 0.737 |
| Fick cardiac index, l/min/m 2 | 2.4 ± 0.5 | 2.4 ± 0.9 | 0.963 |
A total of 63 patients (24 PS and 39 TOF) had complete and technically adequate cardiac MRI data (mean 2.2 ± 2.7 months from the initial evaluation; Table 4 ). To ensure similarity of this selected cohort to the entire study population, baseline demographic data were recompared, with no significant differences observed. As with the entire cohort, patients with TOF in this subgroup were substantially more likely to have a pervious history of palliative shunt placement.
| Variable | Pulmonic Stenosis (n = 24) | Tetralogy of Fallot (n = 39) | p Value |
|---|---|---|---|
| Age, years | 45.9 ± 13.3 | 46.2 ± 11.7 | 0.304 |
| Male | 11 (46%) | 23 (59%) | 0.435 |
| Body mass index, kg/m 2 | 27.5 ± 6.3 | 27.1 ± 6.3 | 0.783 |
| Time from surgery to MRI, years | 36 ± 11 | 32 ± 9 | 0.152 |
| Shunt | 4% | 46% | <0.001 |
| New York Heart Association class | 1.6 ± 0.6 | 1.5 ± 0.6 | 0.786 |
| Body surface area, m 2 | 1.96 ± 0.28 | 1.91 ± 0.24 | 0.489 |
| Right ventricular end-diastolic volume, ml | 267.1 ± 77.7 | 256.3 ± 112.0 | 0.691 |
| Right ventricular end-diastolic volume indexed, ml/m 2 | 147.9 ± 58.8 | 139.2 ± 61.7 | 0.592 |
| Right ventricular end-systolic volume, ml | 134.5 ± 52.7 | 151.8 ± 97.0 | 0.394 |
| Right ventricular end-systolic volume indexed, ml/m 2 | 73.3 ± 31.2 | 82.5 ± 49.7 | 0.389 |
| Right ventricular ejection fraction, % | 49.1 ± 7.7 | 40.8 ± 11.0 | 0.001 |
| Left ventricular end-diastolic volume, ml | 150.5 ± 34.4 | 158.1 ± 48.1 | 0.584 |
| Left ventricular end-diastolic volume index, ml/m 2 | 79.3 ± 14.8 | 83.3 ± 24.6 | 0.466 |
| Left ventricular end-systolic volume, ml | 61.8 ± 15.7 | 78.4 ± 36.3 | 0.028 |
| Left ventricular end-systolic volume index, ml/m 2 | 31.7 ± 7.9 | 41.3 ± 19.0 | 0.015 |
| Left ventricular ejection fraction, % | 59.3 ± 7.1 | 52.1 ± 9.6 | 0.002 |
| Pulmonic regurgitation, % | 32.3 ± 18.9 | 37.3 ± 21.6 | 0.394 |
| Aortic regurgitation, % | 2.8 ± 6.4 | 4.3 ± 4.5 | 0.341 |
| Root diameter, cm | 3.1 ± 0.3 | 4.0 ± 0.6 | <0.001 |
| Ascending diameter, cm | 3.0 ± 0.6 | 3.6 ± 0.8 | 0.054 |
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