Analysis of perioperative and long-term outcomes among presentations of anomalous left coronary artery from the pulmonary artery diagnosed beyond infancy versus during infancy

Analysis of perioperative and long-term outcomes among presentations of anomalous left coronary artery from the pulmonary artery diagnosed beyond infancy versus during infancy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Analysis of perioperative and long-term outcomes among presentations of anomalous left coronary artery from the pulmonary artery diagnosed beyond infancy versus during infancy Nadine Straka, Kimberlee Gauvreau, Yisong Huang, Elizabeth DeWitt, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3310766/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Dec, 2023 Read the published version in Pediatric Cardiology → Version 1 posted 8 You are reading this latest preprint version Abstract Background Anomalous Left Coronary Artery from the Pulmonary Artery (ALCAPA) typically presents in infancy; however, there are cases of patients who survive the infant period and present later in life. We aimed to characterize patients with late ALCAPA diagnoses and to assess perioperative and functional outcomes. Methods A retrospective chart review of patients who underwent ALCAPA repair between 1996 to 2020 at Boston Children’s Hospital was performed. This cohort was divided into early ALCAPA (<1 year) and late ALCAPA (≥ 1 year) groups. Perioperative data were collected. Longitudinal functional assessments were made by echocardiography, exercise stress test, and cardiac magnetic resonance imaging. Results The median age of the late ALCAPA group was 7.6 years with 25% (6/24) of patients over 18 years. The late ALCAPA group was more likely to present as an incidental finding (63%) and required less preoperative intervention compared to the early group. On preoperative echocardiogram, the late ALCAPA group had less moderate or severe mitral regurgitation (16.7% vs 62%, p<0.001) or left ventricular dysfunction (16.7% vs 89%, p <0.001) compared to the early group. Reoperation was uncommon and both groups demonstrated almost complete resolution of mitral regurgitation and left ventricular dysfunction over time. Conclusion There are important differences between late and early ALCAPA subtypes. Revascularization results in excellent outcomes in both early and late groups but long-term surveillance of ALCAPA patients is warranted as they may have functional deficits after repair. ALCAPA anomalous left coronary artery from the pulmonary artery late presentation mitral regurgitation left ventricular dysfunction outcomes Figures Figure 1 Introduction Anomalous origin of the Left Coronary Artery from the Pulmonary Artery (ALCAPA) is a rare congenital anomaly that typically presents in the first year of life [ 1 ]. As the pulmonary vascular resistance falls, shunting of blood from the anomalous coronary artery to the pulmonary artery results in myocardial ischemia [ 2 ]. However, if sufficient collateralization occurs, these patients survive infancy and may present much later. Regardless of the age of presentation, the management of ALCAPA requires surgical intervention to reestablish a dual coronary artery system through reimplantation of the anomalous coronary artery into the aorta [ 3 ]. This procedure is generally associated with an excellent prognosis [ 2 ]. Studies of the late ALCAPA population have been limited in their follow-up data. In this single center study, we aimed to further characterize the perioperative characteristics and outcomes in patients greater than 1 year of age presenting with ALCAPA as well as add more knowledge of the longitudinal functional data to help inform clinical practices. We hypothesized that patients who present with ALCAPA after 1 year of age will have distinct clinical characteristics compared to those who present in infancy. Patients and Methods Patient selection All patients who underwent repair of the anomalous left coronary artery from pulmonary artery to establish antegrade flow from the ascending aorta at a tertiary care center between January 1996 to Dec 2020 were included in our study; follow-up data was collected until March 30, 2023. Patients with anomalous right coronary arteries or associated complex intracardiac disease were excluded. All data was deidentified. This study was conducted retrospectively from data obtained for clinical purposes. The Institutional Review Board at Boston Children’s Hospital determined that our study did not need ethical approval and was granted an IRB waiver of consent. Variable Selection Demographic data included age, weight, and gender. Prematurity was defined as gestational age less than 37 weeks and was noted if the subject presented before 1 year of age. Preoperative factors included presenting symptoms, diagnostic studies (cardiac catheterization vs cardiac magnetic resonance imaging (MRI)), need for intubation, inotropic support, preoperative days to repair, length of stay (LOS). Preoperative electrocardiograms (ECG) were assessed by a single electrophysiologist for the presence of Q waves, ST segment changes, T wave inversion, left ventricular hypertrophy (LVH), and right ventricular hypertrophy (RVH). Operative factors included type of revascularization (direct reimplantation vs. Takeuchi procedure), concomitant mitral valvuloplasty, cardiopulmonary bypass time, cross-clamp time, whether circulatory arrest was performed, delayed sternal closure, and use of postoperative inotropic support. Outcome Measures Primary outcomes measures were 30-day mortality and need for postoperative mechanical circulatory support. Secondary outcomes were postoperative complications, hospital LOS, and need for reoperation. Complications were divided into the following categories: arrhythmias, infections, cardiac arrest with return of spontaneous circulation; and respiratory problems. Functional outcomes included follow-up echocardiography, assessing for presence of left ventricular dysfunction (LVD) and mitral regurgitation (MR); exercise stress test, and cardiac MRI looking for signs of ischemia. Echocardiography reports were reviewed at distinct intervals relative to ALCAPA repair: preoperatively, at discharge, approximately 1 year after discharge, and at the most recent follow-up. Reported findings include left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic volume (LVEDV), fractional shortening and/or ejection fraction, severity of MR, and severity of LVD. Both MR and LVD were classified as follows: none (includes trivial), mild (includes mild-moderate), moderate (includes moderate-severe), and severe. The LVD and MR classes were dichotomized into groups based on severity: non-severe (which included none and mild) and severe (which included moderate and severe) dysfunction. Z-scores were extrapolated based on age and body surface area [ 4 ]. Statistical Analysis Categorical variables are summarized using frequencies and percentages, and continuous variables using medians with interquartile ranges (25th ,75th percentile) unless otherwise noted. Demographic, preoperative, and operative characteristics and outcomes were compared for patients with late vs early ALCAPA using Fisher’s exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. Analyses were performed using Python version 3.0 [ 5 ]. Alluvial diagrams were generated using R (version R4.1.0) to depict changes in MR and LVD [ 6 ]. Results Study population and demographics Between 1996 and 2020, 108 patients with a diagnosis of anomalous coronary arteries were identified. Of 82 patients with isolated coronary anomalies, 69 had isolated ALCAPA, which constituted the study cohort (Supplemental Fig. 1). The diagnosis of ALCAPA was made by echocardiography or by cardiac catheterization (35%, 24/69) and confirmed by intraoperative inspection. Patient Demographics Demographic characteristics of early vs late ALCAPA groups are shown in Table 1 . The two groups varied significantly in their age and weight. The late ALCAPA group was 7.6 (4.2,19.1) years with a median weight of 27.1(16.9, 56.1) kg, while the median age of the early ALCAPA group was 3.4 (2.3, 4.8) months, and median weight was 4.9 (4.4, 5.7) kg (p < 0.001). The age distribution is shown in Supplemental Table 1. There was a female predominance in both early and late ALCAPA groups. Table 1 Characteristics of patients presenting with late and early diagnoses of ALCAPA ALCAPA < 1 year (n = 45) ALCAPA ≥ 1 year (n = 24) P-value Demographics Age (years) 0.3 (0.2, 0.4) 7.6 (4.2, 19.1) < 0.001 Age (months) 3.4 (2.3, 4.8) 90.7 (50.3, 228.9) Weight (kg) 4.9 (4.4, 5.7) 27.1 (16.9, 56.1) < 0.001 Female 30 (66.7%) 19 (79.2%) 0.40 Premature 2 (4.4%) 0 1.0 Presenting symptom Congestive heart failure 28 (62.2%) 3 (12.5%) < 0.001 Asymptomatic 1 (2.2%) 15 (62.5%) < 0.001 Respiratory distress 8 (17.8%) 0 0.044 Shock 4 (8.8%) 0 0.29 Failure to thrive 4 (8.8%) 0 0.29 Cardiac arrest 0 1 (4.2%) 0.35 Chest pain 0 5 (20.8%) 0.004 Diagnostic studies Cardiac catheterization 9 (20.0%) 15 (62.5%) 0.001 Cardiac MRI 1 (2.2%) 6 (25.0%) 0.006 Preoperative Support Intubation 12 (26.7%) 1 (4.2%) 0.03 Inotropic support 16 (35.6%) 1 (4.2%) 0.003 EKG findings n = 32 n = 21 Q wave 7 (21.9%) 3 (14.3%) 0.72 ST Depression 1 (3.1%) 0 1.0 ST Elevation 4 (12.5%) 0 0.14 ST Non-specific changes 7 (21.9%) 3 (14.3%) 0.72 T wave inversion 20 (62.5%) 2 (9.5%) < 0.001 Left Ventricular Hypertrophy 20 (62.5% 4 (19.0%) 0.002 Preoperative Echo LVEDD Z-score 7.53 (5.54, 8.43), n = 14 2.72 (1.66, 4.10), n = 11 0.006 LVEDV Z-score 7.17 (5.68, 9.29), n = 31 2.87 (1.81, 4.70), n = 16 < 0.001 EF Z-score -7.57 (-8.35, -6.21), n = 30 -1.53 (-3.56, -0.10), n = 18 < 0.001 FS Z-score -10.36 (-12.58, -8.63), n = 14 -1.89 (-3.50, 0.15), n = 11 < 0.001 MR ≥ moderate 28 (62.2%) 4 (16.7%) < 0.001 LVD ≥ moderate 40 (88.9%) 4 (16.7%) < 0.001 All values are listed as n (%) or median with Interquartile range (25th,75th percentile) LVEDD = Left Ventricular End Diastolic Diameter, LVEDV = Left Ventricular End Diastolic Volume, EF = Ejection Fraction, FS = Fractional Shortening, MR = Mitral Regurgitation, LVD = Left ventricular dysfunction Preoperative characteristics Preoperative characteristics are shown in Table 1 . Compared to the early ALCAPA group, the late group was significantly more likely to present with chest pain (21% vs 0%, p = 0.004) or as an asymptomatic incidental finding (63% vs 2%; p < 0.001). One patient in the late ALCAPA group presented following a cardiac arrest. The early ALCAPA group was more likely to present with symptoms of congestive heart failure (62% vs 13%; p < 0.001) or respiratory distress (18% vs 0%; p = 0.04), compared to the late ALCAPA group. The late ALCAPA group was less likely to require intubation (4% vs 27%; p = 0.03) or inotropic support (4% vs 36%; p = 0.003), compared to the early group. The late ALCAPA group was less likely to have significant findings on EKG compared to the early group, notably with less T wave inversion (10% vs 63%; p < 0.001) and left ventricular hypertrophy (19% vs 63%; p = 0.002). On preoperative echocardiogram, the late ALCAPA group had smaller LVEDD Z-scores (2.72 vs 7.53, p = 0.006) and LVEDV Z-scores (2.87 vs 7.17, p < 0.001). The late ALCAPA group also had more preserved function with higher ejection fraction Z-scores (-1.53 vs -7.57, p < 0.001), and fractional shortening Z-scores (-1.89 vs -10.36, p < 0.001). Finally, the late group had a significantly lower proportion of patients with moderate or greater mitral regurgitation (17% vs 62%, p < 0.001) and left ventricular dysfunction (17% vs 89%, p < 0.001). Perioperative characteristics Perioperative characteristics are outlined in Table 2 . The majority of patients underwent direct reimplantation of the anomalous left coronary artery (97%, 67/69). Two patients had the Takeuchi procedure, one in each late and early ALCAPA groups. There were no significant differences in cardiopulmonary bypass times, cross-clamp times, or need for circulatory arrest between groups. The late ALCAPA group was less likely to have delayed sternal closure (64% (29/45) vs. 0%, p < 0.001) or require postoperative inotropic support (42% (10/24) vs. 93% (39/45), p < 0.001), compared to the early group. Mitral valvuloplasty performed at the time of the index repair was not significantly different between early and late groups. The characteristics of the 17 patients who underwent mitral valvuloplasty are shown in Supplemental Table 2; most were younger than 1 year, had greater than moderate MR, and severe LVD. Table 2 Perioperative Characteristics of patients presenting with late and early diagnoses of ALCAPA ALCAPA < 1 year (n = 45) ALCAPA ≥ 1 year (n = 24) P-value Days to repair 2.0 (1.0–3.0) 64.5 (12.3, 95.0) < 0.001 Operative factors Direct reimplantation 44 (97.8%) 23 (95.8%) 1.0 Takeuchi 1 (2.2%) 1 (4.2%) 1.0 Mitral valvuloplasty 14 (31.1%) 3 (12.5%) 0.14 Cardiopulmonary bypass time(min) 124 (95,179), n = 36 107 (83,137), n = 24 0.11 Cross-clamp time(min) 68 (51,89), n = 36 67 (49,85), n = 24 0.88 Circulatory arrest 4 (8.9%) 2 (8.3%) 1.0 Delayed sternal closure 29 (64.4%) 0 (0%) < 0.001 Postoperative inotropic support 39 (92.9%), n = 42 10 (41.7%) < 0.001 Mortality within 30 days 1 (2.2%) 0 1.0 ECMO 4 (8.9%) 0 0.29 Postoperative complications Any complication 12 (26.7%) 5 (20.8%) 0.77 Arrhythmia 1 (2.2%) 2 (8.3%) 0.28 Infection 4 (8.9%) 0 0.29 Cardiac arrest 3 (6.7%) 0 0.55 Respiratory 2 (4.4%) 2 (8.3%) 0.61 Total hospital LOS (days) 17.8 (13.2, 23.9) 5.2 (4.3, 6.8) < 0.001 Discharge echo LVEDD Z score 3.25 (1.47, 4.46), n = 8 1.81 (-0.40, 2.27), n = 5 0.21 LVEDV Z score 4.84 (3.63, 6.31), n = 33 0.23 (-0.65, 2.39), n = 14 < 0.001 EF Z score -7.48 (-8.51, -4.18), n = 32 -1.60 (-2.96, -0.17), n = 14 < 0.001 FS Z score -12.78 (-16.4, -6.04), n = 7 -2.34 (-3.57, -0.34), n = 8 0.009 MR ≥ moderate 12 (26.7%) 2 (8.3%) 0.12 LVD ≥ moderate 35 (77.8%) 3 (12.5%) < 0.001 Reoperation 7 (16.3%), n = 43 1 (4.2%), n = 24 0.24 Days to reoperation 2190 (173, 6574) 8 (n/a) n/a All values are listed as n (%) or median with Interquartile range (25th,75th percentile) LVEDD = Left Ventricular End Diastolic Diameter, LVEDV = Left Ventricular End Diastolic Volume, EF = Ejection Fraction, FS = Fractional Shortening, MR = Mitral Regurgitation, LVD = Left ventricular dysfunction Table 3 Follow-up functional studies of patients presenting with late and early diagnoses of ALCAPA ALCAPA < 1 year ALCAPA ≥ 1 year P-value Exercise stress test n = 13 n = 13 Years since repair 16.0 (11.0, 18.1) 2.1 (0.7, 6) < 0.001 ECG changes 4 (30.8%) 3 (23.1%) 1.0 Symptoms with exercise 0 3 (23.1%) 0.22 Exercise tolerance below average 6 (46.2%) 4 (30.8%) 0.69 Inappropriate HR response 1 (7.7%) 3 (23.1%) 0.59 Inappropriate BP response 1 (7.7%) 3 (23.1%) 0.59 Inappropriate stroke volume response 2 (15.4%) 5 (38.5%) 0.38 Cardiac MRI n = 7 n = 4 Years since repair 13.5 (2.0, 19.3) 6.2 (5.0, 6.7) 0.30 Late gadolinium enhancement 6 (85.7%) 2 (50.0%) 0.49 Regional wall motion abnormalities 3 (42.9%) 1 (25.0%) 1.0 Reimplanted LCA patent 6 (85.7%) 4 (100%) 1.0 Ejection fraction 56.7 (48.8, 66.6) 63.5 (61.7, 65.4) 0.30 All values are listed as n (%) or median with Interquartile range (25th ,75th percentile) Postoperative Outcomes There was one death in our study cohort in the early ALCAPA group. This patient was a 5-week-old premature infant whose aortic valve was damaged during the diagnostic cardiac catheterization prompting emergent repair and ECMO cannulation. In terms of mechanical support, a total of four patients required postoperative ECMO, all of whom were under 1 year and had severe LVD at presentation (6%, 4/69; see Supplemental Table 3). The late ALCAPA group had a shorter total hospital length of stay compared to the early group (Table 2 ). Postoperative complications were generally uncommon in both groups. At discharge, the late ALCAPA group was more likely to have a smaller LVEDD Z-score (1.81 vs 3.25, p = 0.21), higher EF Z-score (-1.60 vs -7.48, p < 0.001), higher FS Z-score (-2.34 vs -12.78, p = 0.009), and less LVD (13% vs 78%, p < 0.001), compared to the early group. The need for reoperation was uncommon, with no difference between groups. About 12% (8/69) of patients required reoperation and are detailed in Supplemental Table 4. Only two (2/8, 25%) of these reoperations occurred within 30 days of the index operation. One patient was listed for heart transplant which was performed at about 1 year postoperatively. Follow-up Echocardiogram results Follow-up echocardiogram time points included the one-year post-discharge echo (median of 311 (198, 389) days in the early ALCAPA group vs 339 (182, 490) days in the late group) and most recent follow-up (median of 8.5 (4.8,14.6) years in the early ALCAPA group vs 5.9 (5.3, 6.8) years in the late group). Sequential echocardiograms demonstrate sustained improvement of MR and LVD in both early and late groups (See Fig. 1, details in Supplemental Table 5). At the one-year follow up, none of the late ALCAPA group had worse than moderate LVD (0% vs 11.1%) or MR (0% vs 7.4%), compared to the early group. On the most recent echo, one patient in the late ALCAPA group developed worse than moderate MR compared to 2 patients in the early ALCAPA group (7.1% vs 8.3%) and no patients had LVD that was worse than moderate. A subgroup of patients had follow-up functional testing including exercise stress tests (n = 26) and cardiac MRI (n = 11). The time since repair was significantly shorter in the late ALCAPA group compared to the early group (median of 2.1 vs 16.0 years for exercise stress tests and 6.2 vs 13.5 years for cardiac MRI, in the late vs early groups, respectively). The late ALCAPA group tended to have more symptoms with exercise (23% vs 0%) as well as an inappropriate heart rate (23% vs 8%), blood pressure (23% vs 8%), and stroke volume (39% vs 15%) response to exercise, but these differences were not statistically significant. The early ALCAPA group tended to have more below average exercise tolerance compared to the late group. In the subgroup who had follow-up cardiac MRI, almost all patients demonstrated patency of the anomalous implanted coronary artery (91%, 10/11). Both groups demonstrated some functional impairment on MRI; notably, the late ALCAPA group was less likely to have evidence of late gadolinium enhancement compared to the early group (86% vs 50%; p = 0.49), but these differences were not statistically significant. Discussion Our study highlights important clinical differences in patients who present with ALCAPA after their first year of life compared to those who present during infancy. The late ALCAPA group was more likely to be asymptomatic or present with chest pain; importantly, one patient presented in cardiac arrest. The late ALCAPA group was also more likely to have preserved function preoperatively, with no mortality or need for ECMO. On follow-up exercise stress tests and cardiac MRI, there was evidence of impairment in both early and late presenters. In our cohort, about 35% (24/69) of patients presented beyond infancy; this proportion is similar to other studies [ 7 , 8 ]. The incidence of ALCAPA has been estimated to be about 1/300,000 live births [ 1 ], however recent studies focusing on late ALCAPA diagnoses suggest that this number may be an underestimate. Patients with ALCAPA who present in cardiac arrest may be missed and only be discovered post-mortem [ 9 ]. Further, in a review of all published case reports of adults presenting with ALCAPA, the authors noted an increase in cases in the recent decade which they attributed to advances in noninvasive imaging [ 10 ]. ALCAPA has long been categorized into subtypes based on the distinct symptoms and the age of presentation: the infant and adult subtypes. The infant subtype typically presents at around two months of age when pulmonary vascular resistance drops, resulting in the development of a left to right shunt and severe myocardial ischemia. The adult subtype is dependent on the development of a collateral circulation to the left coronary artery. While this collateral circulation allows for survival into adulthood, it is often insufficient to supply the left ventricle over time, resulting in chronic ischemia. Patients presenting with adult-type ALCAPA are thus at risk of ischemic cardiomyopathies, arrhythmias, and mitral insufficiency. These patients vary in their presentation from asymptomatic, or they may present with dyspnea, chest pain, reduced exercise tolerance, and sudden cardiac death. Importantly, in our late ALCAPA cohort, we report one patient who presented following an out of hospital cardiac arrest. Comparatively, a recent multicenter study reported out of hospital cardiac arrest in 11% of patients with a late ALCAPA diagnosis [ 7 ]. Another case review suggested that 18% of patients with an adult ALCAPA diagnosis presented with life threatening symptoms. Given the increased risk for cardiac arrest in patients with a late ALCAPA presentation, another interesting finding to highlight is the time to repair in this group. In our study, the late ALCAPA group waited a median of 64.5 days (12.3, 95.0) for surgery to establish dual coronary circulation versus the early ALCAPA group who waited a median of 2 days. Other studies have also demonstrated a longer time to repair after making the diagnosis of late ALCAPA compared to infants [ 7 ]. Time to repair likely reflects severity of presentation in the infant group compared to the late ALCAPA group. The American Heart Association (AHA) guidelines advocate strongly for repair even in asymptomatic patients due to the lifelong risk of ongoing ischemia, ventricular arrhythmias, and sudden cardiac death [ 11 ], however there is no guidance on the optional time to repair for semi-elective cases. Further, there seems to be variation in management despite this guideline. A recent case review noted that 37% of patients with ALCAPA older than 50 years of age were managed medically [ 10 ]. This same study demonstrated that the risk of sudden death during childhood and early adulthood is high, but declines after age 50 years, likely due to a robust collateral circulation. Given the increase in medical morbidity and the increased surgical risk that comes with age, decision on surgical intervention may be patient and provider specific with some opting to forgo surgery, despite AHA guidelines on establishing dual coronary system even in asymptomatic patients. In fact, Lotman et al. proposed a new classification system where in addition to the infant and adult subtypes, they add an asymptomatic adult onset type, which presents beyond the seventh decade of life with mild symptoms or as an incidental finding, and may be managed medically [ 12 ]. In addition to the consideration of timing of repair in patients diagnosed with late ALCAPA, there is little guidance on mitral valve intervention. In our cohort, only about 17% (4/24) of late ALCAPA patients presented with moderate or severe MR compared to about 62% (28/45) in the early ALCAPA group. Of the late ALCAPA group, about 13% (3/24) underwent mitral valvuloplasty compared to 31% (14/45) of patients in the early ALCAPA group. Most studies have focused specifically on mitral valve repair in infants where MR is related to enlargement of the mitral annulus due to LV dilation and ischemia of the papillary muscles. Once coronary revascularization is restored, LV function improves, the mitral annulus size decreases, and MR improves [ 13 ]. Therefore, most surgeons elect only to intervene on the mitral valve when there are structural abnormalities present, or if a patient cannot be weaned from cardiopulmonary bypass. Late ALCAPA patients typically present with some degree of MR from chronic ischemia with preserved function and without significant LV dilation. This population may gain more benefit from reintervention because the MR is unlikely to recover following coronary revascularization [ 14 ]. As a result, some authors suggest that older ALCAPA patients with moderate or severe MR but preserved LV function should be considered for mitral valvuloplasty at the time of repair [ 7 ]. Despite recovery of left ventricular function following ALCAPA repair, the effects of myocardial ischemia may persist. Some studies have demonstrated abnormal myocardial strain at long-term follow-up after ALCAPA repair [ 15 , 16 ]. Others have demonstrated the presence of wall motion abnormalities and perfusion deficits at 10 years following repair, despite complete recovery of left ventricular function [ 17 ]. Further, the effect of the degree of collateralization at presentation on chronic perfusion deficits is unknown. We describe MRI and exercise stress test findings in a sample of late ALCAPA presenters. While limited by sample size, our study suggests that late presenters were more likely to have impaired physiologic responses to exercise but less likely to have evidence of ischemia on MRI compared to those with an early diagnosis of ALCAPA. Interestingly, a previous study also demonstrated that myocardial deficiencies were unrelated to general physical performance in patients who underwent ALCAPA repair [ 17 ]. However, comparison of these groups is difficult because the time from repair to perfusion imaging/stress test was much longer in the early ALCAPA compared to the late ALCAPA group. This is because the late ALCAPA group can readily participate in these studies directly after repair due to their age and ability to comply, which is not the case for the infant population. Regardless, our findings suggest that there may be persistent functional deficits that require life-long monitoring following ALCAPA repair. Limitations Our single center study is limited by its small sample size; however, ALCAPA is a rare disease and our cohort size is comparable to other single-center studies. This affected our ability to detect statistical differences between groups. In our study, we report about 45% loss to follow-up after discharge, which was similar in the early and late ALCAPA groups (47% vs. 42%, respectively). The loss to follow-up in our sample is attributed to the retrospective study design and our institution’s status as a quaternary referral center serving many out-of-state patients. However, it is likely that these patients would have returned to our center if an intervention was needed. Finally, echocardiogram measurements were extracted from the medical record after the images had been read by various cardiologists rather than a single reviewer. Further, some echocardiogram report summaries were limited studies and the original images were not available for review. We elected to use the qualitative measures of MR and LVD from the clinical reports in our analysis as they were the most consistently available. For comparison across groups, we also used Z-scores of echo measurements given the age range in our study population, knowing that these have less relevance for our adult population. Similarly, stress tests and cardiac MRIs were extracted from the medical record and were limited to the published reports available. Conclusion There are important differences between late and early ALCAPA subtypes. Revascularization results in excellent outcomes in both early and late groups, with normalization of function within 1 year of repair in most patients. The timing of repair warrants further investigation as patients with late ALCAPA are at risk of sudden cardiac death. Long-term surveillance of ALCAPA patients is warranted as some may demonstrate functional deficits long after repair. Declarations Funding No funding was received to assist with the preparation of this manuscript. Competing interests The authors have no relevant financial or non-financial interests to disclose. Ethics approval This research study was conducted retrospectively from data obtained for clinical purposes. We consulted extensively with the Internal Review Board (IRB) of Boston Children’s Hospital who determined that our study did not need ethical approval and an IRB official waiver of ethical approval was granted from the IRB of Boston Children’s Hospital (IRB #P00024042, approval date 9/30/2016, last continuing review 2/17/2023). Consent, Data, Material and/or Code availability Non-applicable. A waiver of ethical approval was granted by the IRB of Boston Children’s Hospital as noted above. Authors’ contribution statements N.S. conceptualized and designed the study, designed the data collection system, collected data, analyzed data, and wrote the manuscript text. R.T. and M.N. helped conceptualize and design the study, supervised data collection, and critically reviewed the manuscript. K.G. reviewed the data analysis and critically reviewed and revised the manuscript. E.D. reviewed all electrocardiograms and critically reviewed and revised the manuscript. C.A. critically reviewed and revised the manuscript. Y.H. created Figure 2 and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. References Keith, J.D., The anomalous origin of the left coronary artery from the pulmonary artery. Br Heart J, 1959. 21 (2): p. 149-61. Dodge-Khatami, A., C. Mavroudis, and C.L. Backer, Anomalous origin of the left coronary artery from the pulmonary artery: collective review of surgical therapy. Ann Thorac Surg, 2002. 74 (3): p. 946-55. Backer, C.L., et al., Anomalous origin of the left coronary artery from the pulmonary artery: Successful surgical strategy without assist devices. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu, 2000. 3 : p. 165-172. Z-Score Calculator . [cited 2023 June 13]; Available from: https://zscore.chboston.org/. Van Rossum, G., & Drake, F. L. (2009). Python 3 Reference Manual. , Python 3 Reference Manual . 2009, Scotts Valley, CA: CreateSpace. Team, R.C. R: A language and environment for statistical computing. . 2014; Available from: http://www.R-project.org/. Kwiatkowski, D.M., et al., Characteristics and Surgical Outcomes of Patients With Late Presentation of Anomalous Left Coronary Artery From the Pulmonary Artery: A Multicenter Study. Semin Thorac Cardiovasc Surg, 2021. 33 (1): p. 141-150. Straka, N., et al., Factors Associated With Adverse Outcomes After Repair of Anomalous Coronary From Pulmonary Artery. Ann Thorac Surg, 2019. 108 (3): p. 785-791. Krexi, L. and M.N. Sheppard, Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), a forgotten congenital cause of sudden death in the adult. Cardiovasc Pathol, 2013. 22 (4): p. 294-7. Yau, J.M., et al., Anomalous origin of the left coronary artery from the pulmonary artery in adults: a comprehensive review of 151 adult cases and a new diagnosis in a 53-year-old woman. Clin Cardiol, 2011. 34 (4): p. 204-10. Stout, K.K., et al., 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation, 2019. 139 (14): p. e637-e697. Lotman, E.M., et al., Late adult presentation of ALCAPA syndrome: need for a new clinical classification? A case report and literature overview. Eur Heart J Case Rep, 2020. 4 (6): p. 1-5. Brown, J.W., et al., Does the degree of preoperative mitral regurgitation predict survival or the need for mitral valve repair or replacement in patients with anomalous origin of the left coronary artery from the pulmonary artery? J Thorac Cardiovasc Surg, 2008. 136 (3): p. 743-8. Radman, M., et al., Intermediate Outcomes After Repair of Anomalous Left Coronary Artery From the Pulmonary Artery. Ann Thorac Surg, 2021. 112 (4): p. 1307-1315. Cabrera, A.G., et al., Outcomes of anomalous left coronary artery from pulmonary artery repair: beyond normal function. Ann Thorac Surg, 2015. 99 (4): p. 1342-7. Di Salvo, G., et al., Left Ventricular Mechanics in Patients with Abnormal Origin of the Left Main Coronary Artery from the Pulmonary Trunk Late after Successful Repair. Cardiology, 2017. 136 (2): p. 71-76. Schmitt, B., et al., Myocardial perfusion, scarring, and function in anomalous left coronary artery from the pulmonary artery syndrome: a long-term analysis using magnetic resonance imaging. Ann Thorac Surg, 2014. 98 (4): p. 1425-36. Additional Declarations No competing interests reported. Supplementary Files Supplementaldata.docx Cite Share Download PDF Status: Published Journal Publication published 15 Dec, 2023 Read the published version in Pediatric Cardiology → Version 1 posted Editorial decision: Major revision 25 Sep, 2023 Reviews received at journal 19 Sep, 2023 Reviewers agreed at journal 05 Sep, 2023 Reviewers agreed at journal 01 Sep, 2023 Reviewers invited by journal 01 Sep, 2023 Editor assigned by journal 31 Aug, 2023 Submission checks completed at journal 31 Aug, 2023 First submitted to journal 30 Aug, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3310766","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":230126082,"identity":"071edfd9-bc11-4f8c-99b0-0a87f201c550","order_by":0,"name":"Nadine Straka","email":"data:image/png;base64,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","orcid":"","institution":"Boston Children’s Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Nadine","middleName":"","lastName":"Straka","suffix":""},{"id":230126085,"identity":"1cb37c59-287c-4ac0-9bd9-93c7fa93d91b","order_by":1,"name":"Kimberlee Gauvreau","email":"","orcid":"","institution":"Boston Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kimberlee","middleName":"","lastName":"Gauvreau","suffix":""},{"id":230126086,"identity":"8812cc1a-3edc-4d37-993c-20141630f046","order_by":2,"name":"Yisong Huang","email":"","orcid":"","institution":"Boston Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yisong","middleName":"","lastName":"Huang","suffix":""},{"id":230126088,"identity":"39af9d84-b72e-4279-964f-2240444701b9","order_by":3,"name":"Elizabeth DeWitt","email":"","orcid":"","institution":"Boston Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Elizabeth","middleName":"","lastName":"DeWitt","suffix":""},{"id":230126089,"identity":"5324136c-f079-4e0c-bf66-f6177fa0fa1b","order_by":4,"name":"Catherine Allan","email":"","orcid":"","institution":"Boston Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Catherine","middleName":"","lastName":"Allan","suffix":""},{"id":230126090,"identity":"aac539a0-18f4-48e3-9f89-cddd6490a704","order_by":5,"name":"Ravi Thiagarajan","email":"","orcid":"","institution":"Boston Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ravi","middleName":"","lastName":"Thiagarajan","suffix":""},{"id":230126091,"identity":"fd708b15-1454-4a43-bdcf-f9e1bbeff554","order_by":6,"name":"Meena Nathan","email":"","orcid":"","institution":"Boston Children’s Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Meena","middleName":"","lastName":"Nathan","suffix":""}],"badges":[],"createdAt":"2023-08-30 15:29:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3310766/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3310766/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00246-023-03344-1","type":"published","date":"2023-12-15T15:00:53+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":42678869,"identity":"65c473c9-a973-4801-82fb-f725b2990aad","added_by":"auto","created_at":"2023-09-06 01:18:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":79923,"visible":true,"origin":"","legend":"\u003cp\u003eAlluvial plots for Left Ventricular Dysfunction (LVD) (1a) and Mitral Regurgitation (MR) (1b). The x-axis labels are the visits by sequence: preoperative, postoperative, 1-year follow-up, and most recent follow up. The strata at each visit are degrees of LVD or MR: Severe, Moderate, Mild, None. The alluvia, the horizontal splines span the width of the plot is the frequency of degrees during each visit, indicated by its fill color. The segments of the alluvia between pairs of adjacent axes are flows.\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3310766/v1/07864ec5e342854073d7f137.png"},{"id":48401263,"identity":"427e0790-539f-483a-88a7-7dab02d16111","added_by":"auto","created_at":"2023-12-18 15:05:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":770987,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3310766/v1/af8e5023-f7c3-47c3-b0cc-fce611e3193e.pdf"},{"id":42678870,"identity":"e4d2e14c-76b5-4c9e-9a73-7bb873e0fb4e","added_by":"auto","created_at":"2023-09-06 01:18:46","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":44739,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaldata.docx","url":"https://assets-eu.researchsquare.com/files/rs-3310766/v1/7c26841f8c01819ff1b1a344.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of perioperative and long-term outcomes among presentations of anomalous left coronary artery from the pulmonary artery diagnosed beyond infancy versus during infancy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnomalous origin of the Left Coronary Artery from the Pulmonary Artery (ALCAPA) is a rare congenital anomaly that typically presents in the first year of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. As the pulmonary vascular resistance falls, shunting of blood from the anomalous coronary artery to the pulmonary artery results in myocardial ischemia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, if sufficient collateralization occurs, these patients survive infancy and may present much later. Regardless of the age of presentation, the management of ALCAPA requires surgical intervention to reestablish a dual coronary artery system through reimplantation of the anomalous coronary artery into the aorta [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This procedure is generally associated with an excellent prognosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies of the late ALCAPA population have been limited in their follow-up data. In this single center study, we aimed to further characterize the perioperative characteristics and outcomes in patients greater than 1 year of age presenting with ALCAPA as well as add more knowledge of the longitudinal functional data to help inform clinical practices. We hypothesized that patients who present with ALCAPA after 1 year of age will have distinct clinical characteristics compared to those who present in infancy.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003eAll patients who underwent repair of the anomalous left coronary artery from pulmonary artery to establish antegrade flow from the ascending aorta at a tertiary care center between January 1996 to Dec 2020 were included in our study; follow-up data was collected until March 30, 2023. Patients with anomalous right coronary arteries or associated complex intracardiac disease were excluded. All data was deidentified. This study was conducted retrospectively from data obtained for clinical purposes. The Institutional Review Board at Boston Children\u0026rsquo;s Hospital determined that our study did not need ethical approval and was granted an IRB waiver of consent.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eVariable Selection\u003c/h2\u003e \u003cp\u003eDemographic data included age, weight, and gender. Prematurity was defined as gestational age less than 37 weeks and was noted if the subject presented before 1 year of age. Preoperative factors included presenting symptoms, diagnostic studies (cardiac catheterization vs cardiac magnetic resonance imaging (MRI)), need for intubation, inotropic support, preoperative days to repair, length of stay (LOS). Preoperative electrocardiograms (ECG) were assessed by a single electrophysiologist for the presence of Q waves, ST segment changes, T wave inversion, left ventricular hypertrophy (LVH), and right ventricular hypertrophy (RVH). Operative factors included type of revascularization (direct reimplantation vs. Takeuchi procedure), concomitant mitral valvuloplasty, cardiopulmonary bypass time, cross-clamp time, whether circulatory arrest was performed, delayed sternal closure, and use of postoperative inotropic support.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measures\u003c/h2\u003e \u003cp\u003ePrimary outcomes measures were 30-day mortality and need for postoperative mechanical circulatory support. Secondary outcomes were postoperative complications, hospital LOS, and need for reoperation. Complications were divided into the following categories: arrhythmias, infections, cardiac arrest with return of spontaneous circulation; and respiratory problems. Functional outcomes included follow-up echocardiography, assessing for presence of left ventricular dysfunction (LVD) and mitral regurgitation (MR); exercise stress test, and cardiac MRI looking for signs of ischemia.\u003c/p\u003e \u003cp\u003eEchocardiography reports were reviewed at distinct intervals relative to ALCAPA repair: preoperatively, at discharge, approximately 1 year after discharge, and at the most recent follow-up. Reported findings include left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic volume (LVEDV), fractional shortening and/or ejection fraction, severity of MR, and severity of LVD. Both MR and LVD were classified as follows: none (includes trivial), mild (includes mild-moderate), moderate (includes moderate-severe), and severe. The LVD and MR classes were dichotomized into groups based on severity: non-severe (which included none and mild) and severe (which included moderate and severe) dysfunction. Z-scores were extrapolated based on age and body surface area [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eCategorical variables are summarized using frequencies and percentages, and continuous variables using medians with interquartile ranges (25th ,75th percentile) unless otherwise noted. Demographic, preoperative, and operative characteristics and outcomes were compared for patients with late vs early ALCAPA using Fisher\u0026rsquo;s exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. Analyses were performed using Python version 3.0 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Alluvial diagrams were generated using R (version R4.1.0) to depict changes in MR and LVD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and demographics\u003c/h2\u003e \u003cp\u003eBetween 1996 and 2020, 108 patients with a diagnosis of anomalous coronary arteries were identified. Of 82 patients with isolated coronary anomalies, 69 had isolated ALCAPA, which constituted the study cohort (Supplemental Fig.\u0026nbsp;1). The diagnosis of ALCAPA was made by echocardiography or by cardiac catheterization (35%, 24/69) and confirmed by intraoperative inspection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient Demographics\u003c/h2\u003e \u003cp\u003eDemographic characteristics of early vs late ALCAPA groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The two groups varied significantly in their age and weight. The late ALCAPA group was 7.6 (4.2,19.1) years with a median weight of 27.1(16.9, 56.1) kg, while the median age of the early ALCAPA group was 3.4 (2.3, 4.8) months, and median weight was 4.9 (4.4, 5.7) kg (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The age distribution is shown in Supplemental Table\u0026nbsp;1. There was a female predominance in both early and late ALCAPA groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients presenting with late and early diagnoses of ALCAPA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALCAPA\u0026thinsp;\u0026lt;\u0026thinsp;1 year (n\u0026thinsp;=\u0026thinsp;45)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eALCAPA\u0026thinsp;\u0026ge;\u0026thinsp;1 year (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDemographics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3 (0.2, 0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.6 (4.2, 19.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.4 (2.3, 4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90.7 (50.3, 228.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.9 (4.4, 5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.1 (16.9, 56.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (79.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremature\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePresenting symptom\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongestive heart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (62.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsymptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory distress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (17.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShock\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFailure to thrive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac arrest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (20.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiagnostic studies\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac catheterization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac MRI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative Support\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInotropic support\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (35.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEKG findings\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;32\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;21\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQ wave\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (21.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eST Depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eST Elevation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eST Non-specific changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (21.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT wave inversion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (62.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft Ventricular Hypertrophy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (62.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (19.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative Echo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDD Z-score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.53 (5.54, 8.43), n\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.72 (1.66, 4.10), n\u0026thinsp;=\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDV Z-score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.17 (5.68, 9.29), n\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.87 (1.81, 4.70), n\u0026thinsp;=\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEF Z-score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-7.57 (-8.35, -6.21), n\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.53 (-3.56, -0.10), n\u0026thinsp;=\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFS Z-score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-10.36 (-12.58, -8.63), n\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.89 (-3.50, 0.15), n\u0026thinsp;=\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMR\u0026thinsp;\u0026ge;\u0026thinsp;moderate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (62.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVD\u0026thinsp;\u0026ge;\u0026thinsp;moderate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (88.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAll values are listed as n (%) or median with Interquartile range (25th,75th percentile)\u003c/p\u003e \u003cp\u003eLVEDD\u0026thinsp;=\u0026thinsp;Left Ventricular End Diastolic Diameter, LVEDV\u0026thinsp;=\u0026thinsp;Left Ventricular End Diastolic Volume, EF\u0026thinsp;=\u0026thinsp;Ejection Fraction, FS\u0026thinsp;=\u0026thinsp;Fractional Shortening, MR\u0026thinsp;=\u0026thinsp;Mitral Regurgitation, LVD\u0026thinsp;=\u0026thinsp;Left ventricular dysfunction\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePreoperative characteristics\u003c/h2\u003e \u003cp\u003ePreoperative characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Compared to the early ALCAPA group, the late group was significantly more likely to present with chest pain (21% vs 0%, p\u0026thinsp;=\u0026thinsp;0.004) or as an asymptomatic incidental finding (63% vs 2%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). One patient in the late ALCAPA group presented following a cardiac arrest. The early ALCAPA group was more likely to present with symptoms of congestive heart failure (62% vs 13%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) or respiratory distress (18% vs 0%; p\u0026thinsp;=\u0026thinsp;0.04), compared to the late ALCAPA group. The late ALCAPA group was less likely to require intubation (4% vs 27%; p\u0026thinsp;=\u0026thinsp;0.03) or inotropic support (4% vs 36%; p\u0026thinsp;=\u0026thinsp;0.003), compared to the early group. The late ALCAPA group was less likely to have significant findings on EKG compared to the early group, notably with less T wave inversion (10% vs 63%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and left ventricular hypertrophy (19% vs 63%; p\u0026thinsp;=\u0026thinsp;0.002). On preoperative echocardiogram, the late ALCAPA group had smaller LVEDD Z-scores (2.72 vs 7.53, p\u0026thinsp;=\u0026thinsp;0.006) and LVEDV Z-scores (2.87 vs 7.17, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The late ALCAPA group also had more preserved function with higher ejection fraction Z-scores (-1.53 vs -7.57, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and fractional shortening Z-scores (-1.89 vs -10.36, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Finally, the late group had a significantly lower proportion of patients with moderate or greater mitral regurgitation (17% vs 62%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and left ventricular dysfunction (17% vs 89%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePerioperative characteristics\u003c/h2\u003e \u003cp\u003ePerioperative characteristics are outlined in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The majority of patients underwent direct reimplantation of the anomalous left coronary artery (97%, 67/69). Two patients had the Takeuchi procedure, one in each late and early ALCAPA groups. There were no significant differences in cardiopulmonary bypass times, cross-clamp times, or need for circulatory arrest between groups. The late ALCAPA group was less likely to have delayed sternal closure (64% (29/45) vs. 0%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) or require postoperative inotropic support (42% (10/24) vs. 93% (39/45), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), compared to the early group. Mitral valvuloplasty performed at the time of the index repair was not significantly different between early and late groups. The characteristics of the 17 patients who underwent mitral valvuloplasty are shown in Supplemental Table\u0026nbsp;2; most were younger than 1 year, had greater than moderate MR, and severe LVD.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePerioperative Characteristics of patients presenting with late and early diagnoses of ALCAPA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALCAPA\u0026thinsp;\u0026lt;\u0026thinsp;1 year (n\u0026thinsp;=\u0026thinsp;45)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eALCAPA\u0026thinsp;\u0026ge;\u0026thinsp;1 year (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDays to repair\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.0 (1.0\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.5 (12.3, 95.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOperative factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDirect reimplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (97.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (95.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTakeuchi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMitral valvuloplasty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (31.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiopulmonary bypass time(min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (95,179), n\u0026thinsp;=\u0026thinsp;36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107 (83,137), n\u0026thinsp;=\u0026thinsp;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCross-clamp time(min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (51,89), n\u0026thinsp;=\u0026thinsp;36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (49,85), n\u0026thinsp;=\u0026thinsp;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCirculatory arrest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelayed sternal closure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (64.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative inotropic support\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (92.9%), n\u0026thinsp;=\u0026thinsp;42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMortality within 30 days\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eECMO\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative complications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny complication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (20.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArrhythmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac arrest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal hospital LOS (days)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.8 (13.2, 23.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2 (4.3, 6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDischarge echo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDD Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.25 (1.47, 4.46), n\u0026thinsp;=\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.81 (-0.40, 2.27), n\u0026thinsp;=\u0026thinsp;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDV Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.84 (3.63, 6.31), n\u0026thinsp;=\u0026thinsp;33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.23 (-0.65, 2.39), n\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEF Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-7.48 (-8.51, -4.18), n\u0026thinsp;=\u0026thinsp;32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.60 (-2.96, -0.17), n\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFS Z score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-12.78 (-16.4, -6.04), n\u0026thinsp;=\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.34 (-3.57, -0.34), n\u0026thinsp;=\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMR\u0026thinsp;\u0026ge;\u0026thinsp;moderate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVD\u0026thinsp;\u0026ge;\u0026thinsp;moderate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (77.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReoperation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (16.3%), n\u0026thinsp;=\u0026thinsp;43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.2%), n\u0026thinsp;=\u0026thinsp;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDays to reoperation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2190 (173, 6574)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (n/a)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003en/a\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAll values are listed as n (%) or median with Interquartile range (25th,75th percentile)\u003c/p\u003e \u003cp\u003eLVEDD\u0026thinsp;=\u0026thinsp;Left Ventricular End Diastolic Diameter, LVEDV\u0026thinsp;=\u0026thinsp;Left Ventricular End Diastolic Volume, EF\u0026thinsp;=\u0026thinsp;Ejection Fraction, FS\u0026thinsp;=\u0026thinsp;Fractional Shortening, MR\u0026thinsp;=\u0026thinsp;Mitral Regurgitation, LVD\u0026thinsp;=\u0026thinsp;Left ventricular dysfunction\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFollow-up functional studies of patients presenting with late and early diagnoses of ALCAPA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALCAPA\u0026thinsp;\u0026lt;\u0026thinsp;1 year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eALCAPA\u0026thinsp;\u0026ge;\u0026thinsp;1 year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExercise stress test\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;13\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;13\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYears since repair\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.0 (11.0, 18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1 (0.7, 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECG changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (23.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptoms with exercise\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (23.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExercise tolerance below average\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInappropriate HR response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (23.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInappropriate BP response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (23.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInappropriate stroke volume response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (15.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (38.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCardiac MRI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003en\u0026thinsp;=\u0026thinsp;4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYears since repair\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.5 (2.0, 19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.2 (5.0, 6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLate gadolinium enhancement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (85.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegional wall motion abnormalities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReimplanted LCA patent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (85.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEjection fraction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.7 (48.8, 66.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.5 (61.7, 65.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAll values are listed as n (%) or median with Interquartile range (25th ,75th percentile)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative Outcomes\u003c/h2\u003e \u003cp\u003eThere was one death in our study cohort in the early ALCAPA group. This patient was a 5-week-old premature infant whose aortic valve was damaged during the diagnostic cardiac catheterization prompting emergent repair and ECMO cannulation. In terms of mechanical support, a total of four patients required postoperative ECMO, all of whom were under 1 year and had severe LVD at presentation (6%, 4/69; see Supplemental Table\u0026nbsp;3).\u003c/p\u003e \u003cp\u003eThe late ALCAPA group had a shorter total hospital length of stay compared to the early group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Postoperative complications were generally uncommon in both groups. At discharge, the late ALCAPA group was more likely to have a smaller LVEDD Z-score (1.81 vs 3.25, p\u0026thinsp;=\u0026thinsp;0.21), higher EF Z-score (-1.60 vs -7.48, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), higher FS Z-score (-2.34 vs -12.78, p\u0026thinsp;=\u0026thinsp;0.009), and less LVD (13% vs 78%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), compared to the early group.\u003c/p\u003e \u003cp\u003eThe need for reoperation was uncommon, with no difference between groups. About 12% (8/69) of patients required reoperation and are detailed in Supplemental Table\u0026nbsp;4. Only two (2/8, 25%) of these reoperations occurred within 30 days of the index operation. One patient was listed for heart transplant which was performed at about 1 year postoperatively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up Echocardiogram results\u003c/h2\u003e \u003cp\u003eFollow-up echocardiogram time points included the one-year post-discharge echo (median of 311 (198, 389) days in the early ALCAPA group vs 339 (182, 490) days in the late group) and most recent follow-up (median of 8.5 (4.8,14.6) years in the early ALCAPA group vs 5.9 (5.3, 6.8) years in the late group). Sequential echocardiograms demonstrate sustained improvement of MR and LVD in both early and late groups (See Fig.\u0026nbsp;1, details in Supplemental Table\u0026nbsp;5). At the one-year follow up, none of the late ALCAPA group had worse than moderate LVD (0% vs 11.1%) or MR (0% vs 7.4%), compared to the early group. On the most recent echo, one patient in the late ALCAPA group developed worse than moderate MR compared to 2 patients in the early ALCAPA group (7.1% vs 8.3%) and no patients had LVD that was worse than moderate.\u003c/p\u003e \u003cp\u003eA subgroup of patients had follow-up functional testing including exercise stress tests (n\u0026thinsp;=\u0026thinsp;26) and cardiac MRI (n\u0026thinsp;=\u0026thinsp;11). The time since repair was significantly shorter in the late ALCAPA group compared to the early group (median of 2.1 vs 16.0 years for exercise stress tests and 6.2 vs 13.5 years for cardiac MRI, in the late vs early groups, respectively). The late ALCAPA group tended to have more symptoms with exercise (23% vs 0%) as well as an inappropriate heart rate (23% vs 8%), blood pressure (23% vs 8%), and stroke volume (39% vs 15%) response to exercise, but these differences were not statistically significant. The early ALCAPA group tended to have more below average exercise tolerance compared to the late group. In the subgroup who had follow-up cardiac MRI, almost all patients demonstrated patency of the anomalous implanted coronary artery (91%, 10/11). Both groups demonstrated some functional impairment on MRI; notably, the late ALCAPA group was less likely to have evidence of late gadolinium enhancement compared to the early group (86% vs 50%; p\u0026thinsp;=\u0026thinsp;0.49), but these differences were not statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study highlights important clinical differences in patients who present with ALCAPA after their first year of life compared to those who present during infancy. The late ALCAPA group was more likely to be asymptomatic or present with chest pain; importantly, one patient presented in cardiac arrest. The late ALCAPA group was also more likely to have preserved function preoperatively, with no mortality or need for ECMO. On follow-up exercise stress tests and cardiac MRI, there was evidence of impairment in both early and late presenters.\u003c/p\u003e \u003cp\u003eIn our cohort, about 35% (24/69) of patients presented beyond infancy; this proportion is similar to other studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The incidence of ALCAPA has been estimated to be about 1/300,000 live births [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], however recent studies focusing on late ALCAPA diagnoses suggest that this number may be an underestimate. Patients with ALCAPA who present in cardiac arrest may be missed and only be discovered post-mortem [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Further, in a review of all published case reports of adults presenting with ALCAPA, the authors noted an increase in cases in the recent decade which they attributed to advances in noninvasive imaging [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eALCAPA has long been categorized into subtypes based on the distinct symptoms and the age of presentation: the infant and adult subtypes. The infant subtype typically presents at around two months of age when pulmonary vascular resistance drops, resulting in the development of a left to right shunt and severe myocardial ischemia. The adult subtype is dependent on the development of a collateral circulation to the left coronary artery. While this collateral circulation allows for survival into adulthood, it is often insufficient to supply the left ventricle over time, resulting in chronic ischemia. Patients presenting with adult-type ALCAPA are thus at risk of ischemic cardiomyopathies, arrhythmias, and mitral insufficiency. These patients vary in their presentation from asymptomatic, or they may present with dyspnea, chest pain, reduced exercise tolerance, and sudden cardiac death. Importantly, in our late ALCAPA cohort, we report one patient who presented following an out of hospital cardiac arrest. Comparatively, a recent multicenter study reported out of hospital cardiac arrest in 11% of patients with a late ALCAPA diagnosis [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Another case review suggested that 18% of patients with an adult ALCAPA diagnosis presented with life threatening symptoms.\u003c/p\u003e \u003cp\u003eGiven the increased risk for cardiac arrest in patients with a late ALCAPA presentation, another interesting finding to highlight is the time to repair in this group. In our study, the late ALCAPA group waited a median of 64.5 days (12.3, 95.0) for surgery to establish dual coronary circulation versus the early ALCAPA group who waited a median of 2 days. Other studies have also demonstrated a longer time to repair after making the diagnosis of late ALCAPA compared to infants [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Time to repair likely reflects severity of presentation in the infant group compared to the late ALCAPA group. The American Heart Association (AHA) guidelines advocate strongly for repair even in asymptomatic patients due to the lifelong risk of ongoing ischemia, ventricular arrhythmias, and sudden cardiac death [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], however there is no guidance on the optional time to repair for semi-elective cases. Further, there seems to be variation in management despite this guideline. A recent case review noted that 37% of patients with ALCAPA older than 50 years of age were managed medically [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This same study demonstrated that the risk of sudden death during childhood and early adulthood is high, but declines after age 50 years, likely due to a robust collateral circulation. Given the increase in medical morbidity and the increased surgical risk that comes with age, decision on surgical intervention may be patient and provider specific with some opting to forgo surgery, despite AHA guidelines on establishing dual coronary system even in asymptomatic patients. In fact, Lotman \u003cem\u003eet al.\u003c/em\u003e proposed a new classification system where in addition to the infant and adult subtypes, they add an asymptomatic adult onset type, which presents beyond the seventh decade of life with mild symptoms or as an incidental finding, and may be managed medically [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition to the consideration of timing of repair in patients diagnosed with late ALCAPA, there is little guidance on mitral valve intervention. In our cohort, only about 17% (4/24) of late ALCAPA patients presented with moderate or severe MR compared to about 62% (28/45) in the early ALCAPA group. Of the late ALCAPA group, about 13% (3/24) underwent mitral valvuloplasty compared to 31% (14/45) of patients in the early ALCAPA group. Most studies have focused specifically on mitral valve repair in infants where MR is related to enlargement of the mitral annulus due to LV dilation and ischemia of the papillary muscles. Once coronary revascularization is restored, LV function improves, the mitral annulus size decreases, and MR improves [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Therefore, most surgeons elect only to intervene on the mitral valve when there are structural abnormalities present, or if a patient cannot be weaned from cardiopulmonary bypass. Late ALCAPA patients typically present with some degree of MR from chronic ischemia with preserved function and without significant LV dilation. This population may gain more benefit from reintervention because the MR is unlikely to recover following coronary revascularization [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. As a result, some authors suggest that older ALCAPA patients with moderate or severe MR but preserved LV function should be considered for mitral valvuloplasty at the time of repair [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite recovery of left ventricular function following ALCAPA repair, the effects of myocardial ischemia may persist. Some studies have demonstrated abnormal myocardial strain at long-term follow-up after ALCAPA repair [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Others have demonstrated the presence of wall motion abnormalities and perfusion deficits at 10 years following repair, despite complete recovery of left ventricular function [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Further, the effect of the degree of collateralization at presentation on chronic perfusion deficits is unknown. We describe MRI and exercise stress test findings in a sample of late ALCAPA presenters. While limited by sample size, our study suggests that late presenters were more likely to have impaired physiologic responses to exercise but less likely to have evidence of ischemia on MRI compared to those with an early diagnosis of ALCAPA. Interestingly, a previous study also demonstrated that myocardial deficiencies were unrelated to general physical performance in patients who underwent ALCAPA repair [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, comparison of these groups is difficult because the time from repair to perfusion imaging/stress test was much longer in the early ALCAPA compared to the late ALCAPA group. This is because the late ALCAPA group can readily participate in these studies directly after repair due to their age and ability to comply, which is not the case for the infant population. Regardless, our findings suggest that there may be persistent functional deficits that require life-long monitoring following ALCAPA repair.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eOur single center study is limited by its small sample size; however, ALCAPA is a rare disease and our cohort size is comparable to other single-center studies. This affected our ability to detect statistical differences between groups. In our study, we report about 45% loss to follow-up after discharge, which was similar in the early and late ALCAPA groups (47% vs. 42%, respectively). The loss to follow-up in our sample is attributed to the retrospective study design and our institution\u0026rsquo;s status as a quaternary referral center serving many out-of-state patients. However, it is likely that these patients would have returned to our center if an intervention was needed. Finally, echocardiogram measurements were extracted from the medical record after the images had been read by various cardiologists rather than a single reviewer. Further, some echocardiogram report summaries were limited studies and the original images were not available for review. We elected to use the qualitative measures of MR and LVD from the clinical reports in our analysis as they were the most consistently available. For comparison across groups, we also used Z-scores of echo measurements given the age range in our study population, knowing that these have less relevance for our adult population. Similarly, stress tests and cardiac MRIs were extracted from the medical record and were limited to the published reports available.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThere are important differences between late and early ALCAPA subtypes. Revascularization results in excellent outcomes in both early and late groups, with normalization of function within 1 year of repair in most patients. The timing of repair warrants further investigation as patients with late ALCAPA are at risk of sudden cardiac death. Long-term surveillance of ALCAPA patients is warranted as some may demonstrate functional deficits long after repair.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received to assist with the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics approval\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis research study was conducted retrospectively from data obtained for clinical purposes. We consulted extensively with the Internal Review Board (IRB) of Boston Children\u0026rsquo;s Hospital who determined that our study did not need ethical approval and an IRB official waiver of ethical approval was granted from the IRB of Boston Children\u0026rsquo;s Hospital (IRB #P00024042, approval date 9/30/2016, last continuing review 2/17/2023).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent, Data, Material and/or Code availability\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNon-applicable. A waiver of ethical approval was granted by the IRB of Boston Children\u0026rsquo;s Hospital as noted above.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors\u0026rsquo; contribution statements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eN.S. conceptualized and designed the study, designed the data collection system, collected data, analyzed data, and wrote the manuscript text.\u003c/p\u003e\n\u003cp\u003eR.T. and M.N. helped conceptualize and design the study, supervised data collection, and critically reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003eK.G. reviewed the data analysis and critically reviewed and revised the manuscript.\u003c/p\u003e\n\u003cp\u003eE.D. reviewed all electrocardiograms and critically reviewed and revised the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eC.A. critically reviewed and revised the manuscript.\u003c/p\u003e\n\u003cp\u003eY.H. created Figure 2 and reviewed and revised the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKeith, J.D., \u003cem\u003eThe anomalous origin of the left coronary artery from the pulmonary artery.\u003c/em\u003e Br Heart J, 1959. \u003cstrong\u003e21\u003c/strong\u003e(2): p. 149-61.\u003c/li\u003e\n\u003cli\u003eDodge-Khatami, A., C. Mavroudis, and C.L. Backer, \u003cem\u003eAnomalous origin of the left coronary artery from the pulmonary artery: collective review of surgical therapy.\u003c/em\u003e Ann Thorac Surg, 2002. \u003cstrong\u003e74\u003c/strong\u003e(3): p. 946-55.\u003c/li\u003e\n\u003cli\u003eBacker, C.L., et al., \u003cem\u003eAnomalous origin of the left coronary artery from the pulmonary artery: Successful surgical strategy without assist devices.\u003c/em\u003e Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu, 2000. \u003cstrong\u003e3\u003c/strong\u003e: p. 165-172.\u003c/li\u003e\n\u003cli\u003e\u003cem\u003eZ-Score Calculator\u003c/em\u003e. [cited 2023 June 13]; Available from: https://zscore.chboston.org/.\u003c/li\u003e\n\u003cli\u003eVan Rossum, G., \u0026amp; Drake, F. L. (2009). Python 3 Reference Manual. , \u003cem\u003ePython 3 Reference Manual\u003c/em\u003e. 2009, Scotts Valley, CA: CreateSpace.\u003c/li\u003e\n\u003cli\u003eTeam, R.C. \u003cem\u003eR: A language and environment for statistical computing. \u003c/em\u003e. 2014; Available from: http://www.R-project.org/.\u003c/li\u003e\n\u003cli\u003eKwiatkowski, D.M., et al., \u003cem\u003eCharacteristics and Surgical Outcomes of Patients With Late Presentation of Anomalous Left Coronary Artery From the Pulmonary Artery: A Multicenter Study.\u003c/em\u003e Semin Thorac Cardiovasc Surg, 2021. \u003cstrong\u003e33\u003c/strong\u003e(1): p. 141-150.\u003c/li\u003e\n\u003cli\u003eStraka, N., et al., \u003cem\u003eFactors Associated With Adverse Outcomes After Repair of Anomalous Coronary From Pulmonary Artery.\u003c/em\u003e Ann Thorac Surg, 2019. \u003cstrong\u003e108\u003c/strong\u003e(3): p. 785-791.\u003c/li\u003e\n\u003cli\u003eKrexi, L. and M.N. Sheppard, \u003cem\u003eAnomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), a forgotten congenital cause of sudden death in the adult.\u003c/em\u003e Cardiovasc Pathol, 2013. \u003cstrong\u003e22\u003c/strong\u003e(4): p. 294-7.\u003c/li\u003e\n\u003cli\u003eYau, J.M., et al., \u003cem\u003eAnomalous origin of the left coronary artery from the pulmonary artery in adults: a comprehensive review of 151 adult cases and a new diagnosis in a 53-year-old woman.\u003c/em\u003e Clin Cardiol, 2011. \u003cstrong\u003e34\u003c/strong\u003e(4): p. 204-10.\u003c/li\u003e\n\u003cli\u003eStout, K.K., et al., \u003cem\u003e2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.\u003c/em\u003e Circulation, 2019. \u003cstrong\u003e139\u003c/strong\u003e(14): p. e637-e697.\u003c/li\u003e\n\u003cli\u003eLotman, E.M., et al., \u003cem\u003eLate adult presentation of ALCAPA syndrome: need for a new clinical classification? A case report and literature overview.\u003c/em\u003e Eur Heart J Case Rep, 2020. \u003cstrong\u003e4\u003c/strong\u003e(6): p. 1-5.\u003c/li\u003e\n\u003cli\u003eBrown, J.W., et al., \u003cem\u003eDoes the degree of preoperative mitral regurgitation predict survival or the need for mitral valve repair or replacement in patients with anomalous origin of the left coronary artery from the pulmonary artery?\u003c/em\u003e J Thorac Cardiovasc Surg, 2008. \u003cstrong\u003e136\u003c/strong\u003e(3): p. 743-8.\u003c/li\u003e\n\u003cli\u003eRadman, M., et al., \u003cem\u003eIntermediate Outcomes After Repair of Anomalous Left Coronary Artery From the Pulmonary Artery.\u003c/em\u003e Ann Thorac Surg, 2021. \u003cstrong\u003e112\u003c/strong\u003e(4): p. 1307-1315.\u003c/li\u003e\n\u003cli\u003eCabrera, A.G., et al., \u003cem\u003eOutcomes of anomalous left coronary artery from pulmonary artery repair: beyond normal function.\u003c/em\u003e Ann Thorac Surg, 2015. \u003cstrong\u003e99\u003c/strong\u003e(4): p. 1342-7.\u003c/li\u003e\n\u003cli\u003eDi Salvo, G., et al., \u003cem\u003eLeft Ventricular Mechanics in Patients with Abnormal Origin of the Left Main Coronary Artery from the Pulmonary Trunk Late after Successful Repair.\u003c/em\u003e Cardiology, 2017. \u003cstrong\u003e136\u003c/strong\u003e(2): p. 71-76.\u003c/li\u003e\n\u003cli\u003eSchmitt, B., et al., \u003cem\u003eMyocardial perfusion, scarring, and function in anomalous left coronary artery from the pulmonary artery syndrome: a long-term analysis using magnetic resonance imaging.\u003c/em\u003e Ann Thorac Surg, 2014. \u003cstrong\u003e98\u003c/strong\u003e(4): p. 1425-36.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"ALCAPA, anomalous left coronary artery from the pulmonary artery, late presentation, mitral regurgitation, left ventricular dysfunction, outcomes","lastPublishedDoi":"10.21203/rs.3.rs-3310766/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3310766/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAnomalous Left Coronary Artery from the Pulmonary Artery (ALCAPA) typically presents in infancy; however, there are cases of patients who survive the infant period and present later in life. We aimed to characterize patients with late ALCAPA diagnoses and to assess perioperative and functional outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective chart review of patients who underwent ALCAPA repair between 1996 to 2020 at Boston Children’s Hospital was performed. This cohort was divided into early ALCAPA (\u0026lt;1 year) and late ALCAPA (≥ 1 year) groups. Perioperative data were collected. Longitudinal functional assessments were made by echocardiography, exercise stress test, and cardiac magnetic resonance imaging.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe median age of the late ALCAPA group was 7.6 years with 25% (6/24) of patients over 18 years. The late ALCAPA group was more likely to present as an incidental finding (63%) and required less preoperative intervention compared to the early group. On preoperative echocardiogram, the late ALCAPA group had less moderate or severe mitral regurgitation (16.7% vs 62%, p\u0026lt;0.001) or left ventricular dysfunction (16.7% vs 89%, p \u0026lt;0.001) compared to the early group. Reoperation was uncommon and both groups demonstrated almost complete resolution of mitral regurgitation and left ventricular dysfunction over time.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere are important differences between late and early ALCAPA subtypes. Revascularization results in excellent outcomes in both early and late groups but long-term surveillance of ALCAPA patients is warranted as they may have functional deficits after repair.\u003c/p\u003e","manuscriptTitle":"Analysis of perioperative and long-term outcomes among presentations of anomalous left coronary artery from the pulmonary artery diagnosed beyond infancy versus during infancy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-09-06 01:18:41","doi":"10.21203/rs.3.rs-3310766/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-09-25T16:23:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-09-19T22:07:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"ffcf51d9-5f80-4d48-9946-bcc38f14c332_SNPRID","date":"2023-09-05T14:48:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"ec67758e-6391-46d3-a2fd-a7d7d945db05","date":"2023-09-01T22:34:41+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-09-01T22:18:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-08-31T13:13:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-08-31T13:13:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Cardiology","date":"2023-08-30T15:19:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d13bbac4-c32d-4c0f-9c4b-c05a7ad8af5b","owner":[],"postedDate":"September 6th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-12-18T15:03:05+00:00","versionOfRecord":{"articleIdentity":"rs-3310766","link":"https://doi.org/10.1007/s00246-023-03344-1","journal":{"identity":"pediatric-cardiology","isVorOnly":false,"title":"Pediatric Cardiology"},"publishedOn":"2023-12-15 15:00:53","publishedOnDateReadable":"December 15th, 2023"},"versionCreatedAt":"2023-09-06 01:18:41","video":"","vorDoi":"10.1007/s00246-023-03344-1","vorDoiUrl":"https://doi.org/10.1007/s00246-023-03344-1","workflowStages":[]},"version":"v1","identity":"rs-3310766","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3310766","identity":"rs-3310766","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}