Author + information
- Tara Karamlou, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Tara Karamlou, Division of Pediatric Cardiac Surgery, 513 Parnassus Avenue, Suite S-549, Benioff Children's Hospital, University of California–San Francisco, San Francisco, California 94143.
Investigation of the influence of surgical timing on early outcomes after operative repair for complex congenital heart disease in term neonates has not led to consensus (1–6). However, with few exceptions, the available studies have focused mainly on infants with hypoplastic left heart and its variants awaiting a Norwood operation (1–6), or on the timing of the subsequent cavopulmonary connection (7–9). We recently reported that infants undergoing a Norwood operation at older than 7 days of age had improved early and intermediate outcomes compared with those infants undergoing surgery when younger than 7 days of age. Our results are in contrast to those of previously published studies, many of which showed older age to be an important risk factor for post-Norwood operation mortality (1–6). Alsoufi et al. (2) reported outcomes of 55 infants older than 14 days of age at their center. They found that age younger than 3 weeks at the time of a Norwood operation was a risk factor for mortality before bidirectional Glenn procedure and for overall mortality, but that those infants older than 2 weeks of age required pulmonary vasodilators and higher inotropic support that translated into ongoing attrition after a bidirectional procedure Glenn (2). Similarly, Hehir et al. (1) studied 313 hospital survivors after a Norwood operation at the Children's Hospital of Philadelphia. They showed that age at operation older than 7 days was a risk factor for interstage death. Importantly, the presence of an intact atrial septum, which was more prevalent in the older infants, was also strongly associated with interstage death. An older report from Mahle et al. (3), also from the Children's Hospital of Philadelphia, found that age older than 14 days at surgery was associated with higher mortality after a Norwood procedure.
Unfortunately, there are no published data to inform the surgical decision regarding the timing of complete repair for neonates with simple transposition of the great arteries (d-TGA) (10). However, if consensus had been achieved in the aforementioned studies, extrapolation of the recommendations from the Norwood population is unlikely to be useful because infants with biventricular circulation have different risk profiles.
In the report by Anderson et al. (11) in this issue of the Journal, the authors performed a single-institution, retrospective review of 140 selected infants ≤ 36 weeks' gestation with d-TGA (with or without a ventricular septal defect) undergoing an arterial switch operation from 2003 through 2012. The authors analyzed the influence of age at surgery (as a dichotomous and continuous predictor) on early “major” morbidity as well as hospital costs. Infants were excluded if the surgical delay was ascribed to an intercurrent pathological process (e.g., infection, intracranial hemorrhage). Major morbidity was defined as cardiac arrest, extracorporeal membrane oxygenation, delayed sternal closure, systemic infection, seizure, stroke on magnetic resonance imaging with clinical sequelae, diaphragmatic paralysis/paresis, reoperation before discharge, or readmission at ≤30 days. Costs were adjusted to account for inflation using the Consumer Price Index. The statistical models were appropriately complex to account for within-patient correlations, multicollinearity among predictor variables, and nonlinear biological systems. The median age at operation was 5 days (range: 1 to 12 days). As expected, age behaved nonlinearly with respect to major morbidity, with a decreasing probability of major morbidity between 1 and 3 days and an increasing probability of major morbidity after 3 days. Specifically, neonates undergoing arterial switch between 1 and 3 days had an incremental benefit of decreasing morbidity (46%) for every day later that surgery was performed, whereas the opposite was true for neonates undergoing arterial switch after 3 days of age. In the “older” cohort, there was an incremental increase in major morbidity (47%) for every day later that surgery was performed. The authors also found costs increased universally among all infants by approximately 8% for every day that surgery was delayed after adjustment for other confounders. The authors inferred that, based on integration of this dual analysis, an arterial switch operation is ideally performed on day of life 3.
The findings of this study are important and very timely considering the increased consideration of outcomes other than mortality after repair of complex congenital heart disease. Although the Society of Thoracic Surgeons recently endorsed several quality metrics, it is not known which structure and process measures have the strongest influence on outcome, and, owing to the relative rarity of many complex lesions, many of the current outcome metrics have a limited ability to identify outliers (12,13). Composite measures combining multiple indicators may address some of these limitations, but remain underdeveloped and problematic due to differential weighting. For the present study, I suspect that if outcomes were weighted as equivalent, older neonates might have had less mortality but a higher prevalence of complications. Second, the relationship between quality (lower prevalence of morbidity and mortality) and cost is unclear. It is not known whether achieving better outcomes requires significant investment of resources or whether there are centers able to achieve optimal outcomes at lower cost (high value). Third, healthcare expenditures have consistently outgrown the economy for decades. It is critical that processes of care be implemented that integrate iterative evaluation of resource use, and therefore deliver more cost-effective care. It should be mentioned that the study by Anderson et al. (11) used a more inclusive definition of major morbidity than that currently endorsed by the Society of Thoracic Surgeons Congenital Heart Surgery Database, therefore hampering direct comparisons with other centers (12,13).
The restriction of the population to a relatively homogeneous group (presence of ventricular septal defect notwithstanding) is an important strength of the present study. Certainly, the presence of other morphological factors such as left ventricular outflow tract obstruction or double-outlet right ventricle that ostensibly alter the perfusion strategy or significantly change the perioperative complication profile could lead to inaccurate conclusions. Incompletely evaluated in the study were the impact of prenatal diagnosis and the implications of transfer from a referring institution, both of which changed substantially over the study period. The authors reported that 85% of patients were transferred to their institution in 2003, whereas only 9% were transferred to their institution in 2012. Despite the fact that costs incurred before transfer were not included in the authors' analysis, infants undergoing transfer before surgical repair had higher total costs. Although no overt relationship was detected in the study, it is possible that infants requiring transfer represented a higher risk physiological or anatomic substrate given the widespread availability of the arterial switch operation for routine d-TGA.
After careful consideration of the study, there are 2 main issues that should be addressed. The first is the question of pathophysiological correlates. In other words, it is disconcerting that, within the window studied (97% of neonates operated on within 10 days of age) where the risk of left ventricular deconditioning is extremely low, there would be an incremental increase per day in major morbidity and cost. Further substantiation by elucidation of an underlying plausible physiological mechanism will be important. The second is the issue of generalizability of findings. Adoption of published practice patterns could lead to different local outcomes because of intangible or unmeasured center-specific effects, underscoring the principle that results from 1 institution may not be generalizable to others. Targeted center-specific internal review, if possible, should precede externally recommended changes in practice.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Karamlou is now affiliated with the Benioff Children's Hospital, University of California–San Francisco, San Francisco, California. Dr. Karamlou has reported that she has no relationships relevant to the contents of this paper to disclose.
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