Two decades after surgery for transposition of the great arteries, the clinical status, cardiac function, cardiorespiratory performance, and neurohormonal activity of patients who underwent either atrial switch (Mustard) operations or arterial switch operations (ASOs) were compared. Sixty-two patients with simple transposition of the great arteries who underwent either Mustard (n = 34) or ASO (n = 28) procedures were included in this cross-sectional study. Following the same study protocol, clinical workup including echocardiography, stress testing, and blood work was completed for all patients. Mean ages in the 2 groups were comparable, at 20.6 ± 2.1 and 20.6 ± 3.4 years in the ASO and Mustard groups, respectively. All ASO patients were in New York Heart Association class I, whereas 59% of Mustard patients were in class II or III. Peak oxygen uptake was higher in ASO patients (percentage of predicted 80% vs 69%, p <0.01). Compared with healthy subjects, the mean Tei index for systemic ventricle was high in the 2 groups, but this parameter was significantly higher in Mustard than ASO patients (0.60 ± 0.16 vs 0.47 ± 0.14, p <0.01). The median plasma N-terminal pro–brain natriuretic peptide level in ASO patients was within the normal range, but the Mustard group had significantly higher levels (42 ng/ml [range 18 to 323] vs 172 ng/ml [range 26 to 1,018], p <0.0001). In conclusion, this cross-sectional assessment 2 decades after surgery reveals better clinical status in patients who underwent ASO compared with Mustard patients. This holds in terms of cardiac function, cardiorespiratory performance, and neurohormonal activity.
With incidence of 5% to 7% among the congenital heart defects, transposition of the great arteries (TGA) is the second most common cyanotic heart defect. In the 1960s, atrial diversion procedures such as the Mustard and Senning procedures revolutionized the prospects for patients with TGA. Since the early 1980s, these procedures have largely been superseded by anatomic repair, the so-called arterial switch operation (ASO). The survival rate 20 years after an atrial switch operation for simple TGA is 80% to 86%, compared with 86% to 96% after an ASO. Each of these surgical techniques is associated with possible long-term sequelae. Mustard patients may have baffle obstructions and chronic right ventricular overload in the systemic position, which may lead to right ventricular dysfunction, arrhythmia, and sudden death, whereas the residual lesions in ASO patients are predominately pulmonary stenosis and aortic valve dysfunction as well as coronary artery complications. Although many studies have found excellent exercise performance in children and adolescents after ASOs, other studies suggest that exercise performance in patients after ASO might deteriorate with increasing age, as is observed in patients after atrial redirection. Therefore, we sought to compare clinical status, cardiac function, cardiorespiratory performance, and neurohormonal activity in adults with TGA who underwent either Mustard or ASO procedures 2 decades ago.
Methods
From 1986 to 1994, a total of 46 patients underwent surgical ASO repair for TGA at Hannover Medical School by the same surgeon (G.Z.). Thirty-four had simple TGA. Twenty-eight of these patients (11 female patients) agreed to participate and completed the study protocol. This time frame was chosen so as to have a minimum follow-up period of 18 years. From May 2003 to May 2004, we evaluated the cardiorespiratory status of 377 adults with operated congenital heart disease at the University of Göttingen (Göttingen, Germany). Thirty-nine patients had undergone Mustard procedures for TGA by 1 surgeon, who was not the Hannover Medical School surgeon. Of this patient group, 34 patients (7 female patients) with simple TGA were chosen on the basis of comparable age at follow-up with the ASO group. We performed a protocol for this cross-sectional study as described in the following discussion. For each patient, the protocol was completed on the same day. The same study protocol was applied to the 2 groups.
The exclusion criteria were acute infection, chronic lung disease, acute or chronic hepatitis, severe mental retardation, and chromosomal syndromes. After adequate explanation of the purpose of the study, informed consent was obtained from all patients. The study protocol was approved by the local ethics committee (Hannover Medical School #5686).
All patients underwent physical examinations and measurements of blood pressure, body weight, and height. A standard 12-lead electrocardiogram was recorded. To include subjectively perceived impairments, we classified patients according to a system proposed by the New York Heart Association.
Spirometry was performed in all subjects before cardiopulmonary exercise testing, with measurements of forced vital capacity and forced expiratory volume in 1 second calculated as percentages of the predicted values, adjusted for age, gender, and body mass. Exercise testing was performed in all patients using an upright bicycle ergometer (Ergometrics 900/911; Ergoline, Bitz, Germany) beginning with a workload of 0.5 W/kg body weight and increasing by 0.5 W/kg every 2 minutes. Oxygen uptake was measured using a breath-by-breath analysis (LF8.5 Ganshorn; Ganshorm Medizin Electronic, Niederlauer, Germany) throughout the exercise procedure. All patients carried out a maximal, symptom-limited (fatigue and/or dyspnea) treadmill exercise test. Peak oxygen uptake (V o 2max ) was determined as the highest value in the terminal phase of exercise. The 12-lead electrocardiogram and heart rate were recorded continuously during the test. Blood pressure was recorded every 2 minutes using a cuff sphygmomanometer. In addition, lactate values were measured at rest and at the end of exercise testing.
Peripheral venous blood samples were obtained from all participants, after resting for ≥15 minutes before exercise testing. The blood samples were immediately placed on ice and subsequently centrifuged at 5,000 rpm for 10 minutes. Plasma and serum aliquots were stored at −80°C until further analysis. N-terminal pro–brain natriuretic peptide, cystatin C, and high-sensitivity C-reactive protein levels were determined using immunoassay (Elecsys 2010; Roche Diagnostics GmbH, Mannheim, Germany). Growth differentiation factor 15 concentrations were determined using immunoradiometric assay, as previously described.
We performed routine transthoracic 2-dimensional, M-mode, and Doppler echocardiography using an iE33 system (Philips Medical Systems, Andover, Massachusetts) interfaced with multifrequency transducers. The Tei index, which has been reported previously, was calculated as the sum of isovolumetric relaxation time and isovolumic contraction time divided by ventricular ejection time. Measurements were done in the usual manner, in the supine position, and the 2-dimensional and Doppler tracings were stored for off-line analysis.
Twenty-six patients (93%) underwent coronary angiography and/or magnetic resonance imaging after ASOs. Because of a lack of accessibility, we were not able to review the coronary angiographic or magnetic resonance imaging results of Mustard patients.
Data were analyzed using PASW Statistics version 18.0 (SPSS, Inc., Chicago, Illinois). Normally distributed continuous variables are reported as mean ± SD and skewed continuous variables as medians and ranges. Independent-samples Student’s t tests or independent-samples Mann-Whitney U tests were used to compare differences in continuous outcomes. A p value <0.05 was accepted as the threshold for statistical significance.
Results
The clinical and demographic characteristics of the 62 patients are listed in Table 1 . Mustard patients were significantly older at surgery. Body mass indexes in the 2 groups were comparable. All ASO patients were in New York Heart Association class I, whereas 59% of Mustard patients were in class II or higher. Except for 12 Mustard patients who had ventricular pacemakers, all patients were in sinus rhythm.
| Variable | ASO (n = 28) | Mustard (n = 34) | p Value |
|---|---|---|---|
| Body mass index (kg/m 2 ) | 23.5 ± 4.2 | 23.3 ± 3 | 0.82 |
| Age (yrs) | 20.6 ± 2.1 | 20.6 ± 3.4 | 0.56 |
| Age at operation (mos) | 0.13 (0.03–12.1) | 10.7 (1.7–76.2) | <0.0001 ∗ |
| Follow-up after operation (yrs) | 20.5 ± 2.1 | 19.3 ± 3.7 | 0.14 |
| New York Heart Association class | <0.0001 ∗ | ||
| I | 28 | 14 | |
| II | 0 | 16 | |
| III | 0 | 4 | |
| Pacemaker | 0 | 12 (43%) | <0.0001 ∗ |
| Heart rate at rest (beats/min) | 77 ± 12 | 74 ± 14 | 0.42 |
| Maximal heart rate (beats/min) | 174 ± 15 | 158 ± 27 | 0.006 ∗ |
| Systolic blood pressure at rest (mm Hg) | 113 ± 17 | 118 ± 11 | 0.20 |
| Maximal systolic blood pressure during exercise (mm Hg) | 180 ± 26 | 178 ± 24 | 0.83 |
| V o 2max (ml/kg/min) | 29.5 ± 5.9 | 26.5 ± 5.4 | 0.05 ∗ |
| V o 2max (% of predicted) | 80 ± 16 | 69 ± 16 | 0.007 ∗ |
| Respiratory exchange ratio | 1.14 ± 0.11 | 1.09 ± 29 | 0.02 ∗ |
| Forced expiratory volume in 1 second (% of predicted) | 84 ± 18 | 95 ± 20 | 0.026 ∗ |
| N-terminal pro–brain natriuretic peptide (ng/ml) | 42 (18–323) | 172 (26–1,018) | <0.0001 ∗ |
| Cystatin C (mg/L) | 0.83 ± 0.12 | 0.80 ± 0.12 | 0.30 |
| High-sensitivity C-reactive protein (mg/L) | 0.74 (0.23–7.17) | 0.91 (0.23–11.5) | 0.49 |
| Growth differentiation factor 15 (ng/L) | 560 (100–1,000) | 468 (343–850) | 0.21 |
| Medications | |||
| β blockers | 0 | 4 | <0.0001 ∗ |
| Digoxin | 0 | 2 | <0.0001 ∗ |
| Angiotensin-converting enzyme inhibitors | 0 | 1 | <0.0001 ∗ |
The reason for reoperations in the Mustard group (for all 5 patients) was baffle obstruction and in the ASO group was pulmonary artery stenosis in 4 patients and patch plasty of the ascending aorta in 1 patient. Patients after ASO underwent interventional procedures for pulmonary artery obstruction (6 patients) more frequently than Mustard patients (1 patient). Two Mustard patients received electrophysiologic intervention for arrhythmia ( Table 2 ).
| Variable | ASO (n = 28) | Mustard (n = 34) | p Value |
|---|---|---|---|
| Reoperation | 5 (18%) | 5 (15%) | 0.65 |
| Intervention | 6 (21%) | 3 (9%) | <0.05 ∗ |
| Residual defects (echocardiography) | |||
| Pulmonary valve stenosis | 13 | 3 | <0.05 ∗ |
| Pulmonary valve regurgitation | 2 | 6 | <0.05 ∗ |
| Subaortic AV valve regurgitation | 0 | 10 | <0.05 ∗ |
| Subpulmonary AV valve regurgitation | 1 | 3 | 0.11 |
| Aortic valve stenosis/dilatation | 3 | 0 | <0.05 ∗ |
| Aortic valve regurgitation | 6 | 0 | <0.05 ∗ |
| Cardiac imaging | |||
| Coronary angiography | 24 | ND | |
| Follow-up after operation (yrs) | 11 (3.8–13.5) | ||
| Magnetic resonance imaging | 17 | ND | |
| Follow-up after operation (yrs) | 19 (18.5–22.5) | ||
| Doppler echocardiography | |||
| Ejection time of system ventricle (ms) | 290 ± 23 | 293 ± 38 | 0.67 |
| Isovolumetric contraction time + isovolumetric relaxation time (ms) | 134 ± 37 | 172 ± 33 | 0.0004 ∗ |
| Tei index of systemic ventricle | 0.47 ± 0.14 | 0.60 ± 0.16 | 0.004 ∗ |
| Ejection fraction of system ventricle (%) | 57 ± 7 | ND |
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