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Influence of intraoperative residual lesions and timing of extracorporeal membrane oxygenation on outcomes following first-stage palliation of single-ventricle heart disease
Data regarding the influence of intraoperative residual lesions on extracorporeal membrane oxygenation (ECMO) following the Norwood procedure are limited. Moreover, the significance of postoperative ECMO timing on in-hospital outcomes remains incompletely characterized.
Methods
This was a single-center, retrospective review of consecutive patients who underwent the Norwood operation from January 1997 to November 2017. Patients with at least minor residual lesions based on the intraoperative postcardiopulmonary bypass echocardiogram were identified. The association between residual lesions and postoperative ECMO was assessed with logistic regression, adjusting for age, weight, prematurity, various preoperative system-specific and procedural risk factors, shunt type, and era. Among patients receiving ECMO, associations between late ECMO (≥3 days post-Norwood) and in-hospital mortality or transplant, postoperative hospital length-of-stay, and cost of hospitalization were evaluated using logistic regression or generalized linear models with a gamma distribution and logarithmic link.
Results
Among 500 patients, 78 (15.6%) received ECMO postoperatively. On multivariable analysis, the presence of at least minor residual lesions (odds ratio, 4.4; 95% CI, 2.1-9.3; P < .001) was associated with postoperative ECMO. In the ECMO subpopulation, there were 44 (56.4%) deaths or transplants. Late ECMO was associated with increased risk of in-hospital mortality or transplant (adjusted odds ratio, 6.2; 95% CI, 1.5-26.0), longer postoperative hospital length of stay (regression coefficient, 0.7; 95% CI, 0.3-1.1), and greater cost (regression coefficient, 0.6; 95%, CI 0.4-0.7), versus early ECMO (all P values < .05).
Conclusions
The presence of even minor intraoperative residua significantly increases the risk of ECMO following the Norwood operation. Among patients receiving ECMO postoperatively, early institution of ECMO is associated with lower mortality and resource utilization.
Among patients receiving ECMO following the Norwood operation, early institution of ECMO is associated with lower in-hospital mortality and resource utilization, compared with late ECMO.
Intraoperative residual lesions significantly increase the risk of receiving ECMO following the Norwood operation. Among neonates cannulated for ECMO postoperatively, ECMO instituted within 2 days of the Norwood operation is associated with a reduced risk of in-hospital mortality or transplant, shorter postoperative hospital length of stay, and lower cost of hospitalization, compared with late ECMO.
Advances in prenatal diagnosis, surgical techniques, and perioperative management have improved outcomes following first-stage palliation of hypoplastic left heart syndrome and other related single-ventricle disorders.
Nevertheless, refractory ventricular failure remains a significant source of major morbidity and mortality postoperatively, and often necessitates extracorporeal membrane oxygenation (ECMO). Support with ECMO may also be indicated for failure to wean from cardiopulmonary bypass (CPB), unexpected cardiac arrest, severe cyanosis, and refractory arrhythmias.
Historically, there has been limited data on the role of ECMO in neonates following the Norwood operation given poor outcomes and limited experience with this complex patient population.
Indication for initiation of mechanical circulatory support impacts survival of infants with shunted single-ventricle circulation supported with extracorporeal membrane oxygenation.
Risk factors for hospital morbidity and mortality after the Norwood procedure: a report from the Pediatric Heart Network Single Ventricle Reconstruction trial.
Recent evidence also suggests that various patient- and procedure-related variables, including low birth weight, longer duration of preoperative mechanical ventilation, and prolonged CPB time, are risk factors for receiving ECMO postoperatively.
Whereas these risk factors aid prognostication of high-risk patients who are likely to require mechanical support, clinicians are nonetheless limited in their ability to prospectively alter the natural history of such patients. This is in part due to the dearth of information regarding modifiable risk factors for ECMO, including the presence of intraoperative residual lesions. Furthermore, the optimal timing of ECMO, especially in patients with borderline hemodynamic status, remains unknown. We therefore sought to evaluate the association between the presence of at least minor residual lesions (based on the post-CPB echocardiogram) and postoperative ECMO, and to better understand the influence of early versus late institution of ECMO on in-hospital outcomes following the Norwood procedure.
Patients and Methods
Patient Population
Clinical and echocardiographic data from consecutive patients who underwent the Norwood procedure (the index operation) at a quaternary referral center between January 1, 1997, and November 1, 2017, were retrospectively reviewed following institutional review board approval (IRB-P00041313; date of approval/exemption: January 20, 2022) and waiver of consent.
Assessment of Residual Lesions
For all patients meeting entry criteria, the intraoperative post-CPB echocardiogram was used to systematically assess residual lesions related to one or more subcomponents of the Norwood operation using the echocardiographic criteria of the Residual Lesion Score.
Among patients transitioned from CPB to ECMO, residual lesions were evaluated using the last echocardiogram performed on CPB before institution of ECMO. Norwood-specific subcomponents included the atrial septum, neoaortic valve, modified Blalock-Taussig shunt (BTS) or right ventricle-pulmonary artery (RV-PA) conduit, coronary arteries or Stansel anastomosis, proximal and distal aortic arch, and branch pulmonary arteries (PAs). If at least 1 of these subcomponents was deemed to be only adequately repaired (eg, mild distal arch stenosis with peak gradient 20-40 mm Hg), patients were described as having a minor residual lesion. Similarly, a designation of major residual lesion was earned if at least 1 of the subcomponents was inadequately addressed (eg, moderate-severe proximal arch obstruction with peak gradient >40 mm Hg or >30% narrowing by color Doppler jet width) (Table E1).
Outcomes, Predictors, and Covariates
In the primary analysis involving the entire Norwood cohort, the outcome of interest was the institution of postoperative ECMO, defined as ECMO initiated at any point between weaning from CPB during the Norwood operation and hospital discharge, predischarge death or transplantation, or second-stage palliation (for patients who remained in-hospital between first- and second-stage palliation). The primary predictor was the presence of at least minor intraoperative residual lesions based on the Residual Lesion Score.
In addition, several patient- and procedure-related covariates were assessed, including age, weight <2.5 kg, prematurity (<37 gestational weeks), presence of noncardiac anomalies, syndromes, or genetic abnormalities, presence of at least 1 major preoperative system-specific risk factor (ie, mechanical ventilation, renal or hepatic failure, cardiopulmonary resuscitation or shock, mechanical circulatory support, stroke, sepsis, and necrotizing enterocolitis), various procedure-specific risk factors (ie, ascending aorta <2 mm, at least moderate left or right atrioventricular valve regurgitation, aortic atresia, intact atrial septum or restrictive atrial septum, defined as an interatrial communication with diameter <3 mm or mean gradient >5 mm Hg across the atrial septum on color Doppler echocardiography or obstructed pulmonary venous return, ventriculocoronary connections or clinical or laboratory evidence of myocardial ischemia, at least moderate dominant ventricular dysfunction, and pulmonary overcirculation with QP/QS > 2), source of pulmonary blood flow (BTS or RV-PA conduit), second CPB run unrelated to residual lesions (eg, bleeding and hemodynamic compromise), and surgical era.
In the secondary analysis involving the subpopulation of postoperative ECMO patients, outcomes of interest included in-hospital (early) mortality or transplant, postoperative hospital length-of-stay (PHLOS), and total inpatient cost of hospitalization. PHLOS was calculated as the number of days from the date of surgery to date of discharge or date of second-stage palliation (for patients who remained in-hospital till second-stage palliation). Inpatient costs were queried from an internal financial database that ties hospital account records with billing information specific to each encounter or patient visit. Costs were related only to inpatient hospital services, including intensive care unit and operating room utilization, medical supplies, laboratory tests and point-of-care evaluations, pharmacy-related services, radiographic and imaging services, and equipment, among others. Costs and fees related to professional services were excluded. All inpatient costs were inflated to the 2021 US dollar using the medical component of the consumer price index. In all secondary analyses, the primary predictor was late ECMO, defined as ECMO instituted on postoperative day 3 and beyond. This threshold was chosen a priori based on post-Norwood hemodynamic states and their associations with mortality
Summary statistics were reported as frequency (percentage) for categorical variables and median (interquartile range [IQR]) for continuous variables. Baseline patient-related and procedure-related characteristics were compared between patients receiving and not receiving ECMO using Fisher exact test or the Wilcoxon rank-sum test. Among patients who received ECMO postoperatively, similar comparisons were made between those who underwent early versus late ECMO. In the primary analysis, the association between postoperative ECMO and the presence of at least minor intraoperative residua was assessed using univariable and multivariable logistic regression models. In the secondary analysis, the associations between late ECMO and in-hospital outcomes were evaluated using univariable and multivariable logistic regression (mortality or transplant) or generalized linear models assuming a gamma distribution with a logarithmic link (PHLOS and cost of hospitalization). Multivariable models adjusted for all covariates chosen a priori. Odds ratios (OR) and regression coefficients were reported with 95% CI. Model discrimination and goodness-of-fit were assessed using the C-statistic and coefficient of determination, respectively. Stata version 15 (StataCorp LLC, College Station, Tex) was used throughout.
Results
Of 500 patients who underwent the Norwood operation, 442 (88.4%) had hypoplastic left heart syndrome and 468 (94.0%) had a right ventricle-dominant circulation. A minority of patients (<10%) had double-outlet right or left ventricle, double-inlet right ventricle, and unbalanced complete atrioventricular canal. Intraoperatively, 47 (9.4%) patients required a second CPB run. Of these 47 patients, 11 (23.4%) were returned to CPB to address residual lesions; the remaining 36 (76.6%) patients were placed back on CPB for bleeding or hemodynamic compromise unrelated to residual lesions. As determined by the final intraoperative post-CPB echocardiogram, 449 (89.8%) patients had no or trivial residual lesions and 51 (10.2%) had minor residual lesions; no patients had major residual lesions before leaving the operating room (Table 1). Postoperatively, 78 (15.6%) patients received ECMO. Of these 78 patients, 10 (12.8%) were transitioned from CPB to ECMO in the operating room and 25 (32.1%) underwent cannulation for ECMO within 4 hours of arriving to the intensive care unit. Patients receiving ECMO were significantly more likely to have longer CPB times, require multiple CPB runs, and have at least 1 minor intraoperative residual lesion, compared with those who did not receive ECMO (all P values < .001). Specifically, neonates receiving ECMO were more likely to have intraoperative residua related to the coronary arteries or Stansel anastomosis (P = .004), BTS or RV-PA conduit (P = .004), and branch PAs (P = .006) (Table 1). Of note, 7 (1.4%) patients within the overall cohort stayed in-hospital between first- and second-stage palliation, none of whom received ECMO at any point during their hospitalizations and all of whom survived to the Fontan operation.
Table 1Baseline patient and surgical characteristics by institution of postoperative extracorporeal membrane oxygenation (ECMO)
Assessed using the echocardiographic criteria of the Residual Lesion Score (residual lesions were evaluated using the intraoperative postcardiopulmonary bypass echocardiogram for the majority of patients, or the echocardiogram performed immediately before institution of ECMO for patients transitioned from bypass to ECMO in the operating room).
Mild or greater obstruction with mean gradient >3 mm Hg.
5 (1.0)
3 (0.7)
2 (2.6)
.18
Neoaortic valve
Mild or greater neoaortic valve regurgitation.
27 (5.4)
19 (4.5)
8 (10.3)
.053
Blalock-Taussig or Sano shunt
Partial or complete shunt occlusion.
3 (0.6)
0 (0)
3 (3.9)
.004
Branch pulmonary artery
Mild or greater stenosis, distortion, or obstruction.
9 (1.8)
4 (1.0)
5 (6.4)
.006
Any
51 (10.2)
31 (7.4)
20 (25.6)
<.001
Values are presented as median (interquartile range) or frequency (%). AVVR, Atrioventricular valve regurgitation; OPVR, obstructed pulmonary venous return.
∗ Comparisons using the Wilcoxon rank-sum test or Fisher exact test.
† <37 gestational weeks.
‡ Seizures, hepatic dysfunction or failure, necrotizing enterocolitis, or shock.
§ QP/QS > 2.
‖ Assessed using the echocardiographic criteria of the Residual Lesion Score (residual lesions were evaluated using the intraoperative postcardiopulmonary bypass echocardiogram for the majority of patients, or the echocardiogram performed immediately before institution of ECMO for patients transitioned from bypass to ECMO in the operating room).
¶ Mild or greater stenosis with peak gradient >20 mm Hg or >30% narrowing by color Doppler jet width.
# At least mild obstruction to coronary flow.
∗∗ Mild or greater obstruction with mean gradient >3 mm Hg.
†† Mild or greater neoaortic valve regurgitation.
‡‡ Partial or complete shunt occlusion.
§§ Mild or greater stenosis, distortion, or obstruction.
On univariable analysis, at least minor residua (OR, 4.3; 95% CI, 2.3-8.1; P < .001), presence of at least 1 major system-specific risk factor (OR, 1.7; 95% CI, 1.0-2.8; P = .038), and need for multiple CPB runs unrelated to residual lesions (OR, 5.9; 95% CI, 2.9-12.0; P < .001) were associated with postoperative ECMO. Each of the procedural risk factors conferred an increased risk of receiving ECMO, but none of these estimates reached statistical significance. In addition, there was no effect of surgical era on need for ECMO. On multivariable analysis, at least minor residua (OR, 4.4; 95% CI, 2.1-9.3; P < .001) and multiple CPB runs unrelated to residual lesions (OR, 5.8; 95% CI, 2.6-12.9; P < .001) were significantly associated with postoperative ECMO (Table 2). The addition of intraoperative residual lesions to the covariates-only model increased model discrimination from 0.717 to 0.750.
Table 2Logistic regression models of postoperative extracorporeal membrane oxygenation
At least minor residual lesion related to one or more subcomponent areas of the Norwood operation as determined by the intraoperative echocardiogram and the echocardiographic criteria of the Residual Lesion Score.
Presence of at least one major preoperative risk factor (mechanical ventilation, shock, cardiopulmonary resuscitation, mechanical circulatory support, renal failure, liver failure, stroke, seizure, sepsis, or necrotizing enterocolitis).
1.7 (1.0, 2.8)
.038
1.2 (0.7, 2.3)
.52
Procedure-related factor
Ascending aorta <2 mm
1.3 (0.6-2.5)
.50
0.9 (0.4-1.9)
.72
Moderate or greater left or right AVVR
1.2 (0.4-3.2)
.74
1.1 (0.4-3.4)
.89
Aortic atresia
1.4 (0.8-2.2)
.21
1.4 (0.7-2.5)
.31
Intact or restrictive atrial septum or OPVR
1.6 (0.9-2.8)
.091
0.9 (0.4-2.0)
.84
Coronary sinusoid or myocardial ischemia
1.5 (0.5-4.0)
.47
1.6 (0.5-5.1)
.41
Moderate or greater dominant ventricular dysfunction
∗ Model C statistic: at least minor residua only, 0.592; covariates only, 0.717; full multivariable model, 0.750.
† At least minor residual lesion related to one or more subcomponent areas of the Norwood operation as determined by the intraoperative echocardiogram and the echocardiographic criteria of the Residual Lesion Score.
‡ Odds for each one day increase in age.
§ Noncardiac anomaly, syndrome, or genetic abnormality.
‖ Presence of at least one major preoperative risk factor (mechanical ventilation, shock, cardiopulmonary resuscitation, mechanical circulatory support, renal failure, liver failure, stroke, seizure, sepsis, or necrotizing enterocolitis).
Of 78 patients who received ECMO in the postoperative period, median time to cannulation was 1 day (IQR, 0-5 days), 50 (64.1%) underwent early cannulation (<3 days post-Norwood: median, 0 days; IQR, 0-1 day; range, 0-2 days), and 28 (35.9%) underwent late cannulation (≥3 days post-Norwood: median, 9 days; IQR, 5-23 days; range, 3-75 days). There were no significant differences in baseline patient and surgical characteristics between the early and late ECMO groups. Patients receiving early ECMO were more likely to have intraoperative residual lesions related to the coronary arteries or Stansel anastomosis, atrial septum, BTS or RV-PA conduit, and branch PAs, whereas those receiving late ECMO were likelier to have residua involving the distal arch and neoaortic valve; however, none of these differences was significant at the 0.05 level (Table E2).
The clinical indications for ECMO are summarized in Table 3. The most common reason for support in the early ECMO group was a low cardiac output state, whereas the majority of patients in the late ECMO group received support for cardiac arrest. An overall nonparametric comparison of the indication for support and timing of ECMO did not yield a significant association (P = .26). Following institution of ECMO, 45 (57.7%) patients had at least 1 residual lesion diagnosed on ECMO and 34 (43.6%) patients underwent an unplanned surgical or transcatheter reintervention to address a residual lesion on ECMO. Among patients who underwent 1 or more reinterventions for residual lesions on ECMO, 27 (79.4%) were successfully decannulated following the reintervention. Partial or complete BTS or RV-PA conduit obstruction was the most frequently diagnosed residual lesion on ECMO (overall and in both the early and late groups). Similarly, the majority of patients who underwent a reintervention on ECMO required BTS or RV-PA conduit revision (Table 3). There was no overall association between timing of ECMO and either the diagnosis of at least 1 residual lesion on ECMO (Fisher exact P = .81) or the requirement for at least one unplanned reintervention on ECMO (P = .80).
Table 3Outcomes of interest, indications, duration, and residual lesions in the extracorporeal membrane oxygenation (ECMO) subpopulation
For reference, within the entire Norwood cohort, there were 66 (13.2%) in-hospital deaths or transplants, median postoperative hospital length of stay was 24 days (interquartile range, 15-41 days), and median cost was $258,000 (interquartile range, $165,000-$396,000); among patients who did not receive ECMO postoperatively, there were 22 (5.2%) in-hospital deaths or transplants, median postoperative hospital length of stay was 21 days (interquartile range, 14-37 days), and median cost was $195,000 (interquartile range, $138,000-$260,000).
At least minor residua, related to one or more anatomic subcomponents of the Norwood operation, diagnosed using echocardiography or cardiac catheterization while on ECMO;
Mild or greater obstruction with mean gradient >3 mm Hg.
3 (3.9)
3 (6.0)
0 (0)
–
Neoaortic valve
Mild or greater neoaortic valve regurgitation.
3 (3.9)
2 (4.0)
1 (3.6)
–
Blalock-Taussig or Sano shunt
Partial or complete shunt occlusion.
32 (41.0)
19 (38.0)
13 (46.4)
–
Branch pulmonary artery
Mild or greater stenosis, distortion, or obstruction.
6 (7.7)
4 (8.0)
2 (7.1)
–
Any
45 (57.7)
28 (56.0)
17 (60.7)
.81
Time to diagnosis of residual lesion (d)
Days from institution of ECMO to first diagnosis of any residual lesion while on ECMO.
0 (0-2)
0 (0-2)
0 (0-1)
.57
Reinterventions for residual lesions on ECMO
Proximal arch
8 (10.3)
6 (12.0)
2 (7.1)
–
Distal arch
5 (6.4)
4 (8.0)
1 (3.6)
–
Coronary arteries or Stansel anastomosis
9 (11.5)
7 (14.0)
2 (7.1)
–
Atrial septum
3 (3.8)
3 (6.0)
0 (0)
–
Neoaortic valve
2 (2.6)
1 (2.0)
1 (3.6)
–
Blalock-Taussig or Sano shunt
24 (30.8)
14 (28.0)
10 (35.7)
–
Branch pulmonary artery
4 (5.1)
2 (4.0)
2 (7.1)
–
Any
34 (43.6)
21 (42.0)
13 (46.4)
.80
Values are presented as median (interquartile range) or frequency (percentage).
∗ Comparisons using Fisher exact test or the Wilcoxon rank-sum test.
† For reference, within the entire Norwood cohort, there were 66 (13.2%) in-hospital deaths or transplants, median postoperative hospital length of stay was 24 days (interquartile range, 15-41 days), and median cost was $258,000 (interquartile range, $165,000-$396,000); among patients who did not receive ECMO postoperatively, there were 22 (5.2%) in-hospital deaths or transplants, median postoperative hospital length of stay was 21 days (interquartile range, 14-37 days), and median cost was $195,000 (interquartile range, $138,000-$260,000).
‡ Ongoing hypotension with escalation of pressor and/or inotropic support.
‖ At least minor residua, related to one or more anatomic subcomponents of the Norwood operation, diagnosed using echocardiography or cardiac catheterization while on ECMO;
¶ Mild or greater stenosis with peak gradient >20 mm Hg or >30% narrowing by color Doppler jet width.
# At least mild obstruction to coronary flow.
∗∗ Mild or greater obstruction with mean gradient >3 mm Hg.
†† Mild or greater neoaortic valve regurgitation.
‡‡ Partial or complete shunt occlusion.
§§ Mild or greater stenosis, distortion, or obstruction.
‖‖ Days from institution of ECMO to first diagnosis of any residual lesion while on ECMO.
Within the ECMO subpopulation, there were 44 (56.1%) deaths or transplants, 14 (18.0%) patients died or underwent transplantation while on ECMO, and 64 (82.1%) patients were successfully decannulated. On univariable analysis, late ECMO, presence of at least 1 major system-specific risk factor, and a composite of various procedural risk factors were significantly associated with in-hospital mortality or transplant (all P values < .05). Upon adjusting for baseline patient risk, the need for an unplanned reintervention for a residual lesion while on ECMO, and clinical indication for ECMO, the odds of in-hospital death or transplant was 6.2 times higher for patients who received ECMO on postoperative day 3 and beyond, compared with those who received early ECMO (OR, 6.2; 95% CI, 1.5-26.0; P = .012). Patients with at least 1 major system-specific risk factor (OR, 4.5; 95% CI, 1.1-18.5; P = .038) and those undergoing multiple CPB runs (OR, 6.9; 95% CI, 1.2-38.1; P = .028) also had a significantly higher risk of in-hospital mortality or transplant on multivariable analysis. On the other hand, ECMO for persistent hypoxemia was independently associated with a reduced risk of death or transplant, compared with ECMO for a low cardiac output state (OR, 0.1; 95% CI, 0.01-0.9; P = .037) (Table 4). Inclusion of timing of ECMO in the covariates-only model increased model discrimination from 0.802 to 0.838.
Table 4Logistic regression models of in-hospital mortality or transplant in the extracorporeal membrane oxygenation (ECMO) subpopulation
Surgical or transcatheter reintervention performed on ECMO for residual lesions that were diagnosed after cannulation for ECMO (all residual lesions were scored as at least “minor” based on the Residual Lesion Score).
Preoperative ascending aorta <2 mm, at least moderate left or right atrioventricular valve regurgitation, aortic atresia, intact or restrictive atrial septum or obstructed pulmonary venous return, ventriculocoronary connection, at least moderate dominant ventricular dysfunction, or pulmonary overcirculation.
∗ Model C statistic: timing of ECMO, 0.610; covariates only, 0.802; full multivariable model, 0.838.
† ECMO instituted on postoperative day 3 and beyond.
‡ Surgical or transcatheter reintervention performed on ECMO for residual lesions that were diagnosed after cannulation for ECMO (all residual lesions were scored as at least “minor” based on the Residual Lesion Score).
¶ Preoperative ascending aorta <2 mm, at least moderate left or right atrioventricular valve regurgitation, aortic atresia, intact or restrictive atrial septum or obstructed pulmonary venous return, ventriculocoronary connection, at least moderate dominant ventricular dysfunction, or pulmonary overcirculation.
The median PHLOS in the entire ECMO subpopulation was 36 days (IQR, 22-63 days) (Figure 1). Late ECMO increased the median PHLOS by a factor of 1.5, compared with early ECMO. On univariable analysis, late ECMO and the most recent surgical era were associated with longer PHLOS, whereas weight <2.5 kg was associated with shorter PHLOS (all P values < .05). The multivariable generalized linear model revealed late ECMO (regression coefficient, 0.7; 95% CI, 0.3-1.1; P < .001), age (regression coefficient, 0.1; 95% CI, 0.02 to 0.10; P = .003), weight at surgery <2.5 kg (regression coefficient –0.6; 95% CI, –1.1 to –0.2; P = .009), and surgical era (2004-2010: regression coefficient, 0.7; 95% CI, 0.2 to 1.2; P = .003; 2010-2017: regression coefficient, 0.7, 95% CI, 0.2 to 1.3; P = .010, vs 1997-2003) to be significantly associated with PHLOS (Table 5). The median cost of hospitalization for patients receiving ECMO postoperatively was $396,000 (Figure 1). ECMO instituted on postoperative day 3 and beyond increased the median cost by a factor of 1.6, versus early ECMO. Late ECMO was significantly associated with increased inpatient cost on both univariable (coefficient, 0.6; 95% CI, 0.4 to 0.7; P < .001) and multivariable analysis (coefficient, 0.6; 95% CI, 0.4 to 0.7; P < .001) (Table 6). Addition of timing of ECMO to the covariates-only model increased the coefficient of determination (R2) from 15.5% to 31.7% and from 12.1% to 41.2%, with regard to PHLOS and cost, respectively.
Figure 1Postoperative hospital length of stay and inpatient cost in the extracorporeal membrane oxygenation (ECMO) subpopulation. Hospital length of stay (left) and associated inpatient costs (right) following the Norwood operation are shown for the early and late ECMO groups. The horizontal line in the middle of each box indicates the median; the top and bottom borders of the box mark the 75th and 25th percentiles, respectively. Whiskers mark the adjacent values, defined as the largest and smallest values not more 1.5 times the interquartile range above and below the 75th and 25th percentiles. Circles indicate outliers. *Comparisons by the Wilcoxon rank-sum test.
Surgical or transcatheter reintervention performed on ECMO for residual lesions that were diagnosed after cannulation for ECMO (all residual lesions were scored as at least “minor” based on the Residual Lesion Score).
Preoperative ascending aorta <2 mm, at least moderate left or right atrioventricular valve regurgitation, aortic atresia, intact or restrictive atrial septum or obstructed pulmonary venous return, ventriculocoronary connection, at least moderate dominant ventricular dysfunction, or pulmonary overcirculation.
∗ Model coefficient of determination (R2): timing of ECMO only, 11.2%; covariates only, 15.5%; full multivariable model, 31.7%.
† ECMO instituted on postoperative day 3 and beyond.
‡ Surgical or transcatheter reintervention performed on ECMO for residual lesions that were diagnosed after cannulation for ECMO (all residual lesions were scored as at least “minor” based on the Residual Lesion Score).
¶ Preoperative ascending aorta <2 mm, at least moderate left or right atrioventricular valve regurgitation, aortic atresia, intact or restrictive atrial septum or obstructed pulmonary venous return, ventriculocoronary connection, at least moderate dominant ventricular dysfunction, or pulmonary overcirculation.
Surgical or transcatheter reintervention performed on ECMO for residual lesions that were diagnosed after cannulation for ECMO (all residual lesions were scored as at least “minor” based on the Residual Lesion Score).
Preoperative ascending aorta <2 mm, at least moderate left or right atrioventricular valve regurgitation, aortic atresia, intact or restrictive atrial septum or obstructed pulmonary venous return, ventriculocoronary connection, at least moderate dominant ventricular dysfunction, or pulmonary overcirculation.
∗ Model coefficient of determination (R2): timing of ECMO only, 33.2%; covariates only, 12.1%; full multivariable model, 41.2%.
† ECMO instituted on postoperative day 3 and beyond.
‡ Surgical or transcatheter reintervention performed on ECMO for residual lesions that were diagnosed after cannulation for ECMO (all residual lesions were scored as at least “minor” based on the Residual Lesion Score).
¶ Preoperative ascending aorta <2 mm, at least moderate left or right atrioventricular valve regurgitation, aortic atresia, intact or restrictive atrial septum or obstructed pulmonary venous return, ventriculocoronary connection, at least moderate dominant ventricular dysfunction, or pulmonary overcirculation.
This study represents our 20-year experience with ECMO following the Norwood operation. We found that the presence of even minor residual lesions, assessed using the intraoperative post-CPB echocardiogram, was significantly associated with postoperative ECMO, adjusting for various patient-related and procedure-specific risk factors. Furthermore, among patients receiving ECMO postoperatively, those who underwent early cannulation (<3 days post-Norwood) had significantly better in-hospital transplant-free survival, shorter PHLOS, and lower cost of hospitalization compared to those receiving late ECMO (Figure 2).
Figure 2Influence of intraoperative residual lesions and timing of extracorporeal membrane oxygenation (ECMO) on outcomes following the Norwood operation. Of 500 patients with hypoplastic left heart syndrome and other related single-ventricle disorders who underwent the Norwood operation between January 1997 and November 2017, 78 (15.6%) received ECMO postoperatively. On multivariable logistic regression, the presence of at least minor intraoperative residual lesions and need for a second cardiopulmonary bypass run were significantly associated with ECMO. Among patients receiving ECMO, 50 (64.1%) were cannulated on postoperative day 0 to 2 and 28 (35.9%) were cannulated on postoperative day 3 and beyond. Patients in the latter group had a significantly greater risk of in-hospital mortality or transplant, longer postoperative hospital length of stay, and higher inpatient cost of hospitalization, even upon adjusting for baseline patient risk, indication for ECMO, and need for reinterventions for residual lesions on ECMO. OR, Odds ratio.
Unsurprisingly, this risk is exacerbated in patients following the Norwood procedure, which carries one of the highest mortality rates among all congenital cardiac operations.
Indication for initiation of mechanical circulatory support impacts survival of infants with shunted single-ventricle circulation supported with extracorporeal membrane oxygenation.
These estimates compare favorably with our experience. At our institution, ECMO was instituted at the discretion of the surgeon for patients cannulated in the operating room, and in collaboration with the cardiac intensivist for those cannulated in the intensive care unit. Indications included low cardiac output syndrome, cardiovascular collapse, persistent hypoxemia, and refractory ventricular arrhythmia. This is of particular relevance when comparing outcomes across institutions and surgical eras because the indication for ECMO following the Norwood operation, although a strong predictor of survival to hospital discharge, remains a moving target.
Our findings corroborate prior work demonstrating that ECMO for hypoxemia and shunt thrombosis portends a much better prognosis compared with support primarily for cardiovascular collapse.
Indication for initiation of mechanical circulatory support impacts survival of infants with shunted single-ventricle circulation supported with extracorporeal membrane oxygenation.
In the present study, ECMO for persistent hypoxemia or acute desaturation was independently associated with approximately 10% of the risk of in-hospital mortality or transplant relative to ECMO for low cardiac output syndrome. Notably, adjusting for baseline patient risk, indication for ECMO, and need for reinterventions for residual lesions on ECMO more than doubled the odds of mortality or transplant associated with late initiation of ECMO, thus suggesting that the clinical indication for mechanical circulatory support and identification and treatment of residual lesions on ECMO may only partially mediate the increased risk of adverse outcomes observed with late institution of ECMO.
There is considerable variability in the literature regarding predictors of ECMO after Norwood surgery. Data from the Single Ventricle Reconstruction trial indicated that birth weight <2.5 kg and need for additional procedures after the index operation are significantly associated with postoperative ECMO.
Risk factors for hospital morbidity and mortality after the Norwood procedure: a report from the Pediatric Heart Network Single Ventricle Reconstruction trial.
In addition, a recent retrospective review of 64 consecutive patients receiving ECMO support after the Norwood operation revealed that ascending aorta <2 mm, longer CPB time, intraoperative shunt revision, and use of an RV-PA conduit were associated with postoperative ECMO (only low birth weight and longer CPB time were independently associated with postoperative ECMO).
We saw a similar association between the need for a second CPB run unrelated to residual lesions (used as a proxy for CPB time) and ECMO in the present study. Among all currently known risk factors, CPB time is the only potentially modifiable variable, and even then, surgeons are often limited by intrinsic anatomic complexity and preoperative risk factors. There are very limited data on the influence of intraoperative residual lesions on the need for postoperative ECMO in the Norwood population. In the present study, patients with at least minor intraoperative residua had an approximately 4-fold increased risk of postoperative ECMO, compared with those with no or trivial residua, underscoring the importance of not only systematically assessing the various subcomponents of the Norwood operation, but also the significance of achieving a perfect repair when anatomically feasible and permissible. It is important to note that residual lesions may persist, evolve, or resurface in patients who are cannulated for ECMO postoperatively, even after intraoperative revision.
Sengupta A, Gauvreau K, Kohlsaat K, Colan SD, Newburger JW, Del Nido PJ, et al. Comparison of intraoperative and discharge residual lesion severity in congenital heart surgery. Ann Thorac Surg. April 6, 2022 [Epub ahead of print]. https://doi.org/10.1016/j.athoracsur.2022.02.081
For instance, approximately half the ECMO subpopulation in this study was diagnosed with at least 1 residual lesion following institution of ECMO, compared with 10% of the overall cohort at the conclusion of the Norwood operation. A high index of suspicion should be maintained to identify such residual lesions because earlier detection may improve rate of decannulation and survival to hospital discharge.
Few studies have evaluated the significance of postoperative ECMO timing on outcomes following pediatric cardiac surgery, and none, to our knowledge, have specifically focused on patients undergoing the Norwood operation.
In a multicenter analysis involving 2908 patients who received ECMO following a range of congenital cardiac operations, those who underwent early cannulation (defined as ECMO within 1 day of the index surgery) did not have a survival advantage, but did require shorter hospital and intensive care unit stays, compared with those who underwent late cannulation.
This is in contrast to our findings, where patients who received late ECMO demonstrated significantly worse in-hospital transplant-free survival and greater resource utilization. Although variations in clinical indications, patient anatomy, and surgical complexity may partially account for these differences, the mechanisms underlying the observed survival benefit remain to be deciphered. It is plausible that early institution of ECMO affords clinicians greater flexibility in detecting hemodynamically significant residual lesions in a timely manner, allowing for prompt reintervention when indicated. In fact, in an earlier report from our institution, 83% of neonates needing postcardiotomy ECMO had residual lesions, and time to diagnosis or correction of these lesions was significantly shorter in survivors of ECMO.
Of note, although we did not observe any associations between timing of ECMO initiation and having at least 1 residual lesion diagnosed on ECMO, and requiring at least 1 unplanned reintervention for a residual lesion while on ECMO, this study was likely underpowered to detect any anatomic subcomponent-specific differences between the early and late groups. Nevertheless, patients in the early ECMO group were more likely to have a newly diagnosed (not intraoperative) residua related to the proximal and distal arch, coronary arteries or Stansel anastomosis, atrial septum, neoaortic valve, and branch PAs, whereas those in the late ECMO group were likelier to have de novo conduit- or shunt-related residua, again highlighting the importance of methodical and prompt identification and resolution of residual lesions in a particularly high-risk cohort.
Limitations
This was a retrospective analysis, and bias may have been introduced due to changes in practice over time. Because this was a single-center study, generalizability of our results may also be limited. Furthermore, residual lesions from each procedural subcomponent of the Norwood operation were scored uniformly under the assumption that all subcomponents had similar significance with regards to postoperative outcomes, including the need for ECMO. This may not always be true in clinical practice, especially because prior work has demonstrated that survival outcomes of ECMO are influenced by the indication for support (eg, hypoxemia related to BTS or RV-PA obstruction vs ventricular failure secondary to arch obstruction). In addition, some residual lesions may not be accurately evaluated during weaning of CPB or transitioning of CPB to ECMO. This has particular significance for patients that left the operating room on ECMO support. Future endeavors will address these limitations, involve larger sample sizes, and assess the influences of postoperative ECMO on interstage mortality and long-term outcomes following the Norwood operation.
Conclusions
The presence of even minor intraoperative residual lesions is significantly associated with the need for ECMO following the Norwood operation. Among patients receiving ECMO during the postoperative period, the timing of ECMO initiation is independently associated with in-hospital mortality and resource utilization.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
All index Norwood operations were first divided into subcomponents, each of which was scored as optimal, adequate, or inadequate using specific echocardiographic criteria. Residual lesion severity was then determined by the highest subcomponent score: Class 1 (no or trivial residua) if all subcomponent scores were optimally repaired; Class 2 (minor residua) if 1 or more subcomponents was only adequately repaired, but none were inadequately repaired; and Class 3 (major residua) if at least 1 subcomponent was inadequately repaired.
Subcomponent
Trivial or no residua
Minor residua
Major residua
Proximal arch reconstruction
No residual stenosis (PG < 20 mm Hg) No apparent narrowing by imaging or color Doppler jet width
Mild stenosis (PG 20-40 mm Hg) <30% Narrowing by imaging or color Doppler jet width
Moderate-severe stenosis (PG > 40 mm Hg) >30% Narrowing by imaging or color Doppler jet width
Distal arch reconstruction
No residual stenosis (PG < 20 mm Hg) No apparent narrowing by imaging or color Doppler jet width
Mild stenosis (PG 20-40 mm Hg) <30% Narrowing by imaging or color Doppler jet width
Moderate-severe stenosis (PG > 40 mm Hg) >30% Narrowing by imaging or color Doppler jet width
Coronary perfusion
Unobstructed proximal coronary artery flow
Mild obstruction to proximal coronary artery flow
Moderate-severe obstruction to proximal coronary artery flow
Atrial septectomy
No or trivial obstruction (MG < 2 mm Hg)
Mild obstruction (MG 3-4 mm Hg)
Moderate-severe obstruction (MG > 4 mm Hg)
BTS or RV-PA conduit
No shunt or conduit occlusion
Partial shunt or conduit occlusion
Complete shunt or conduit occlusion
Neoaortic valve
No valvular regurgitation
Mild neoaortic regurgitation
Moderate-severe neoaortic regurgitation
Branch PA reconstruction
No distortion, obstruction, or stenosis
Mild distortion, obstruction, or stenosis
Moderate-severe distortion, obstruction, or stenosis
PG, Peak gradient; MG, mean gradient; BTS, Blalock-Taussig shunt; RV-PA, right ventricle-pulmonary artery; PA, pulmonary artery.
∗ All index Norwood operations were first divided into subcomponents, each of which was scored as optimal, adequate, or inadequate using specific echocardiographic criteria. Residual lesion severity was then determined by the highest subcomponent score: Class 1 (no or trivial residua) if all subcomponent scores were optimally repaired; Class 2 (minor residua) if 1 or more subcomponents was only adequately repaired, but none were inadequately repaired; and Class 3 (major residua) if at least 1 subcomponent was inadequately repaired.
Assessed using the echocardiographic criteria of the Residual Lesion Score (residual lesions were evaluated using the intraoperative post-cardiopulmonary bypass echocardiogram for the majority of patients, or the echocardiogram performed immediately before institution of ECMO for patients transitioned from bypass to ECMO in the operating room);
Mild or greater obstruction with mean gradient >3 mm Hg.
2 (2.6)
2 (4.0)
0 (0)
.53
Neoaortic valve
Mild or greater neo-aortic valve regurgitation.
8 (10.3)
3 (6.0)
5 (17.9)
.13
Blalock-Taussig or Sano shunt
Partial or complete shunt occlusion.
3 (3.9)
2 (4.0)
1 (3.6)
>.99
Branch pulmonary artery
Mild or greater stenosis, distortion, or obstruction.
5 (6.4)
5 (10.0)
0 (0)
.15
Any
20 (25.6)
13 (26.0)
7 (25.0)
>.99
Values are presented as median (interquartile range) or frequency (%). AVVR, Atrioventricular valve regurgitation; OPVR, obstructed pulmonary venous return.
∗ Comparisons using the Wilcoxon rank-sum test or Fisher exact test.
† <37 gestational weeks.
‡ Seizures, hepatic dysfunction or failure, necrotizing enterocolitis, or shock.
§ QP/QS > 2.
‖ Assessed using the echocardiographic criteria of the Residual Lesion Score (residual lesions were evaluated using the intraoperative post-cardiopulmonary bypass echocardiogram for the majority of patients, or the echocardiogram performed immediately before institution of ECMO for patients transitioned from bypass to ECMO in the operating room);
¶ Mild or greater stenosis with peak gradient >20 mm Hg or any narrowing by color Doppler jet width.
# At least mild obstruction to coronary flow.
∗∗ Mild or greater obstruction with mean gradient >3 mm Hg.
†† Mild or greater neo-aortic valve regurgitation.
‡‡ Partial or complete shunt occlusion.
§§ Mild or greater stenosis, distortion, or obstruction.
Indication for initiation of mechanical circulatory support impacts survival of infants with shunted single-ventricle circulation supported with extracorporeal membrane oxygenation.
Risk factors for hospital morbidity and mortality after the Norwood procedure: a report from the Pediatric Heart Network Single Ventricle Reconstruction trial.
Sengupta A, Gauvreau K, Kohlsaat K, Colan SD, Newburger JW, Del Nido PJ, et al. Comparison of intraoperative and discharge residual lesion severity in congenital heart surgery. Ann Thorac Surg. April 6, 2022 [Epub ahead of print]. https://doi.org/10.1016/j.athoracsur.2022.02.081
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