Super Glenn for staged biventricular repair: impact on left ventricular growth?

Abstract

 

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Objectives

The Super Glenn procedure involves targeted increased in blood flow to left sided heart structures with fenestrated atrial septation. The objective of this study was to examine the outcomes of patients who had this procedure as a part of biventricular staging and specifically evaluate the effect on dimensions of left heart structures.

Methods

Data for patients who had this procedure between 2005 and 2019 were retrospectively identified.

Results

Thirty-seven patients were identified. Most common diagnosis was hypoplastic left heart syndrome in 40% (n = 15). On echocardiography, the median mitral valve z score was −2.26. On cardiac magnetic resonance imaging, median indexed left ventricular end-diastolic volume was 31.5 ml/m² and mitral/tricuspid inflow ratio was 0.35. The median age at Super Glenn was 2.3 years (interquartile range 1.5–3.6) while median weight was 12 kg (interquartile range 9.8–14). There were no early/hospital deaths. The median intensive care unit length of stay was 4 days, and median hospital length of stay was 10 days. Median follow-up for the entire cohort was 3 years (range 15 days to 13.2 years). There was a statistically significant increase in indexed left ventricular dimensions. There were 5 deaths (14%). Three patients (8%) underwent heart transplant. Freedom from death/transplant was 79% at 5 years. Seven patients (19%) needed a reoperation. Twenty-three patients (62%) underwent biventricular conversion after a median of 11.3 months after Super Glenn.

Conclusions

The Super Glenn procedure achieves consistent increase in left ventricular dimensions. This may be a useful strategy to help achieve a successful biventricular circulation in patients with borderline left ventricle. The superiority/non-inferiority of this approach over the conventional Fontan pathway is unclear.

INTRODUCTION

Patients with borderline left heart structures often undergo single ventricle palliation. Though the mid-term outcomes are promising, there is predictable long-term attrition and end-organ damage associated with the Fontan circulation [1]. This necessitates exploration of alternative surgical strategies.

In our unit, we have pursued an approach of aggressive biventricular (BiV) repair for a variety of cardiac anomalies associated with borderline left heart structures [2–5]. These include hypoplastic left heart syndrome (HLHS), right dominant unbalanced atrioventricular canal defects and double outlet right ventricles with small left side. In order to achieve this goal, it is essential to develop an adequately sized left ventricle with optimum function [6]. To stimulate left ventricular growth, we have utilized the concept of ‘Super Glenn’—connecting one lung to the superior vena cava, utilizing a shunt [either aortopulmonary or right ventricle to pulmonary artery (PA)] for the contralateral lung, separating the two branch pulmonary arteries and performing fenestrated atrial septation. This results in a targeted increase in pulmonary blood flow and forces blood across the mitral valve into the left ventricle. Once adequate improvement in left heart dimensions is achieved, these patients can be considered for complete BiV repair.

The objective of this study was to examine the outcomes of patients who had a Super Glenn as part of a BiV repair strategy and specifically evaluate the effect on dimensions of left heart structures.

METHODS

Ethical statement

The study was approved by the Boston Children’s Hospital Institutional Review Board (IRB) which waived the need for parental consent (IRB-P00030977).

Study design

This was a single-centre retrospective analysis of all patients operated at Boston Children’s Hospital (BCH) over a period of 15 years between 2005 and 2019 who underwent the Super Glenn procedure.

Hospital records were reviewed to collect demographic data, diagnosis, and details of surgical procedures. When available, cardiac magnetic resonance imaging (CMRI) data were collected both before and after the Super Glenn procedure. Similarly, echocardiographic data were collected for all patients at both time points. When multiple echocardiography reports were available, the most recent and complete report prior to the Super Glenn procedure was recorded as pre-Super Glenn echo. In addition, all follow-up data focusing on survival, reinterventions (surgical or transcatheter) and achievement of BiV circulation were recorded.

Definition of Super Glenn

The procedure (Fig. 1) consists of (1) superior cavopulmonary connection to the right pulmonary artery (RPA) (pre-existing or new), (2) additional source of pulmonary blood flow to the left pulmonary artery (LPA) either as a systemic-pulmonary artery shunt or right ventricle-pulmonary artery conduit, (3) intrapulmonary septation of the above 2 flows with a fenestrated patch, (4) fenestrated atrial septation, (5) additional procedures to optimize inflow and outflow through the left heart which can include—relief of supra mitral or mitral stenosis, papillary muscle division, resection of endocardial fibroelastosis (EFE), relief of left ventricular outflow tract obstruction, relief of aortic valve stenosis, etc., (6) In addition, minor modifications are made to accommodate individual patient anatomy. For example, in cases of bilateral superior vena cava, the left superior vena cava is divided from the atrium and re-routed to the right superior vena cava directly or by using a graft. In cases of previous Stage 1 Norwood-Sano procedure, the right ventricle-pulmonary artery conduit is retained as the source of additional pulmonary blood flow.

Inclusion criteria

Patients were included in the study if they had a Super Glenn procedure either as a staging procedure for future BiV repair or as a bridge to decision regarding future candidacy for BiV repair.

End-points and follow-up

The primary end-point was change in left ventricular dimensions. Secondary end-points were freedom from death/transplant, freedom from reintervention and achievement of BiV circulation.

Left ventricular dimensions were evaluated on echocardiography and on CMR when available. For each pre- versus post-surgical comparison, patients were included only if they had measurements for that variable made both before and after Super Glenn. Mortality was defined as death occurring after the index operation (Super Glenn). Early death was defined as that occurring within 30 days of the index procedure or before discharge. Reintervention was defined as any cardiac surgery or unplanned non-diagnostic catheterization procedure after the index operation, excluding delayed sternal closure, reoperation for bleeding or mediastinal infection. Follow-up was measured from the date of the index operation. Achievement of BiV circulation was defined as a fully septated heart (barring intentionally left fenestration in the atrial septum with blood circulation in series).

Statistical analysis

Continuous variables are summarized with medians and interquartile ranges (IQR). Categorical variables are presented as absolute and relative frequencies (%). The Wilcoxon signed-rank test was used for comparisons of left ventricular dimensions on CMR and echocardiography pre- versus post-Super Glenn. Freedom from death/transplant and reintervention were estimated using the Kaplan–Meier method. Exploratory analyses examining associations between patient characteristics and preoperative echocardiographic and measurements with time to death or transplant were performed using Cox proportional hazards models. The proportional hazards assumption was evaluated using the Grambsch–Therneau test. Hazard ratios are presented with 95% confidence intervals (CI). The level of significance was set at P-value <0.05. No adjustments were made for multiple comparisons. Statistical analyses were performed with IBM SPSS (Statistics version 24) and Stata version 15 (College Station, TX, USA).

RESULTS

Demographics and baseline characteristics

A total of 37 patients were identified who had a Super Glenn procedure over a period of 15 years (2005–2019). Table 1 demonstrates demographics and baseline characteristics. Majority of the patients were male (65%, n = 24) and the most common diagnoses were HLHS in 40% (n = 15) and right dominant unbalanced atrioventricular canal defects in 38% (n = 14). Almost all patients (97%) had a prior Norwood procedure while 84% patients (n = 31) had a prior Glenn procedure. The most common timing of additional recruitment procedures was at the time of Glenn (27%, n = 10). The most common recruitment procedure included mitral valve repair in 32% and aortic valve repair in 30% patients.

On echocardiography, the median mitral valve z score was −2.26 (IQR −3.15 to −1.68), median left ventricular end-diastolic volume (LVEDV) z score was −3.38 (IQR −3.99 to −2.53) while median aortic valve z score was −2.63 (IQR −3.29 to −1.66). On CMR, median indexed LVEDV was 31.5 ml/m² (IQR 23.9–40.2), median indexed LV mass was 26.1 gm/m² (IQR 19.7–34.9) and mitral/tricuspid inflow ratio was 0.35 (IQR 0.25–0.44). There was diffuse EFE in 24% (n = 9) patients. Median left atrial pressure was 9 mmHg while median LV end-diastolic pressure was 11 mmHg. Median RPA and LPA pressure was 13 mmHg.

Super Glenn

Details of the Super Glenn procedure have been listed in Table 2. The median age at Super Glenn was 2.3 years (IQR 1.5–3.6). There were 22% patients (n = 8) <1 year of age. The median weight at Super Glenn was 12 kg (IQR 9.8–14) with 30% patients (n = 11) <10 kg. The most common source of additional pulmonary blood flow was Blalock–Taussig (BT) shunt in 73% (n = 27) patients. The median size of atrial septal fenestration was 4 mm and the median shunt size was 5 mm. The most common concomitant procedures were mitral valve repair in 51% (n = 19) patients and EFE resection in 27% (n = 10). There were no early/hospital deaths. The median intensive care unit length of stay was 4 days and median hospital length of stay was 10 days. Median follow-up for the entire cohort was 3 years (IQR 1.0–4.5 years) (range 15 days to 13.2 years).

Cardiac magnetic resonance imaging evaluation of left ventricular dimensions

There was a statistically significant increase in indexed left ventricular dimensions (Table 3). Median LVEDV increased from 30.00 ml/m² to 51.96 ml/m² (P < 0.001) and LV end-systolic volume from 11.94 ml/m² to 20.81 ml/m² (P < 0.001). At the same time there was decrease in right ventricular dimensions, though the differences were not statistically significant. There was a statistically significant increase in the ratio of LVEDV and RVEDV from 0.30 to 0.57 (P < 0.001). Also, the mitral to tricuspid inflow ratio improved from 0.33 to 0.82 (P = 0.002). Indexed LV mass increased from 24.38 gm/m² to 35.28 gm/m² (P < 0.001). There was also a concomitant decrease in LV mass/volume ratio from 0.85 to 0.70 (P < 0.001).

In addition, differential PA flow measurements were available in 21 patients (57%). The median RPA flow was 50.64% (IQR 43.79–69.74%) and median LPA flow was 49.35% (IQR 30.25–56.2%).

Echocardiographic evaluation of left ventricular dimensions

Only a limited number of patients had both pre- and post-Super Glenn measurements to compare change in dimensions (Table 4). There was a statistically significant increase in z scores of all measurements of left ventricular dimensions.

Catheterization data

After Super Glenn, the median left atrial pressure was 13 mmHg (IQR 11.5–17) in 21 patients in whom data were available. Median LV end-diastolic pressure was 13 mmHg (IQR 12–16.5) in 17 patients in whom data were available. Median RPA pressure was 18 mmHg (IQR 16–21) in 35 patients and median LPA pressure was also 18 mmHg (IQR 16–22) in 30 patients in whom data were available.

Deaths/transplants

There were 5 deaths (14%). One patient died after Super Glenn and before BiV repair while 4 patients died after BiV repair. Four of the 5 deaths (80%) were within 5 years of starting the BiV repair program (2007–2012). Causes of death were BiV dysfunction (n = 2), multi-organ failure (n = 1) and unknown (n = 2).

Three patients (8%) underwent heart transplant. One underwent transplant after Super Glenn and before BiV repair while 2 patients needed transplant after BiV repair. Two of these 3 patients (67%) were operated within the first 5 years of starting the BiV repair program.

Freedom from death/transplant was 100% at 1 year, 85% at 2 years (95% CI 65–94) and 79% at 5 years (95% CI 56–91) (Fig. 2). Univariable Cox regression identified 2 risk factors associated with death/transplant: higher indexed LV end-systolic volume on pre-Super Glenn magnetic resonance imaging [hazard ratio 1.2 for each 1 ml/m² increase, 95% CI (1.01–1.42), P = 0.035] and size of shunt ≥6 mm [hazard ratio 8.76 versus size 4 mm, 95% CI (1.3–59.2), P = 0.026]. Multivariable analysis was not performed due to the small number of outcome events.

Reinterventions

Seven patients (19%) needed a reoperation of which 3 needed a second reoperation. One patient underwent conversion to a Fontan circulation and subsequently underwent Fontan takedown and BiV repair. Reinterventions included mitral valve repair (n = 5), fenestration of atrial septal defect (n = 3), aortic valve repair (n = 2), EFE resection (n = 2) and 1 procedure each for pulmonary vein stenosis repair, tricuspid valve repair, left ventricular outflow tract obstruction resection, unroofing of coronary sinus, LPA augmentation, BT shunt revision, partial clipping of BT shunt and takedown of BT shunt.

Sixteen patients (43%) needed transcatheter intervention while 5 patients (14%) needed catheterization more than once. Procedures included: coiling of aortopulmonary collaterals (n = 13), dilation with or without stenting of atrial septal fenestration (n = 8), branch PA intervention (n = 4), coiling of right and/or left mammary arteries (n = 4), arch dilation (n = 1) and dilation of BT shunt (n = 1).

Achievement of biventricular circulation

Twenty-three patients (62%) underwent BiV repair after a median of 11.3 months after Super Glenn (IQR 7.4–14.1 months). The cumulative incidence of achievement of BiV circulation was 44% at 1 year (95% CI 29–63%) and 68% at 2 years (95% CI 51–85%) (Fig. 3). After BiV repair, 4 patients died while 2 patients underwent heart transplant. All these 6 patients were operated within the first 5 years of starting the BiV repair program. The remaining 17 patients are alive with a median follow-up of 3.8 years (IQR 3–9 years). Post-BiV repair catheterization data were available in limited number of patients who are alive and might not be representative of the full sample. The median of mean RPA pressure was 24 mmHg (IQR 22.5–32.5) in 5 patients and median of mean LPA pressure was 30 mmHg (IQR 23.5–38.5) in 8 patients.

Patients who did not undergo biventricular repair

Of the 14 patients who did not undergo BiV repair, as mentioned above, 1 patient died, and 1 patient had a transplant. Two patients were not suitable for a BiV repair of which one underwent conversion to a Fontan circulation while the other is listed for heart transplant due to BiV dysfunction. The remaining 10 patients are awaiting BiV repair with a median follow-up of 10 months (IQR 3.2,16 months). Post-Super Glenn CMRI is available in 7 out of 10 patients. These patients demonstrate adequate left ventricular dimensions to consider future BiV repair [median LVEDV (38.7 ml/m²), left ventricular ejection fraction (65.7%) and LV mass (33.4 gm/m²)].

Fate of all 37 patients has been depicted in Fig. 4.

DISCUSSION

This study demonstrates the feasibility of utilizing targeted increase in pulmonary and consequently left ventricular blood flow to achieve improvement of left ventricular dimensions. This strategy can be used as a means to eventually achieve a BiV circulation.

The Fontan circulation is inherently non-physiological. The early to mid-term outcomes after the Fontan operation are satisfactory [7]. Some studies report excellent long-term outcomes with a Fontan circulation [8]. However, other studies report disappointing outcomes [9]. Moreover, end-organ dysfunction, long-term sequalae like plastic bronchitis, protein losing enteropathy, arrhythmias and risk of reoperation significantly affect quality of life [1]. It is also well demonstrated that Fontan patients with a dominant right ventricle perform worse than patients with a dominant left ventricle [8, 10, 11]. To explore alternative treatment strategies, the BiV repair program was started at Boston Children’s Hospital in early 2000’s. In order to achieve BiV repair in patients with small left sided structures, we started using the Super Glenn operation as an interim procedure. We have also utilized this technique in patients with unilateral pulmonary vascular disease to improve their single ventricle candidacy [12]. Partial atrial septation but without augmentation of left-sided flow has been described for patients with unbalanced complete atrioventricular canal defects [13].

It can be argued that the change in ventricular dimensions is just a reflection of a change in loading conditions and septal shift. However, in our study the increase in left heart dimensions were not associated with a simultaneous decrease in the size of right heart dimensions. This suggests that the Super Glenn configuration results in improvement in left heart dimensions due to true volume overload. Also, we have demonstrated improvement in left ventricular mass meaning the ventricle has responded to volume as well as pressure load.

Though in our study, we have consistently demonstrated increase in left ventricular dimensions, it must be stressed that size does not necessarily equate function. Hence, just because the left ventricle is bigger, it does not mean it will function better [4]. Diastolic dysfunction is the Achilles’ heel of successful BiV repair. This is especially relevant in the HLHS subset as these patients often have EFE which results in ventricular non-compliance and diastolic dysfunction. This also reiterates the importance of ancillary procedures to be performed at the time of Super Glenn in the form of EFE resection [3].

The use of the Super Glenn procedure must be exercised with caution. Excessive pulmonary blood flow and/or left atrial hypertension with consequent pulmonary hypertension will be detrimental to candidacy for single ventricle palliation or heart transplant. Even with a BiV circulation, it is desirable for these patients to have normal PA pressures. Thus, careful attention to the pulmonary blood flow component is warranted. Our study showed that shunt size ≥6 mm was a strong predictor of death/transplant. Hence, even in larger patients, over sizing of shunt should be avoided. This is especially detrimental in the setting of atrioventricular valve regurgitation. At all points in the BiV staging pathway, care must be taken that the patient still remains a single ventricle candidate in case the BiV pathway is not successful. At the same time, as evident from our experience, the procedure has a significant learning curve. It should be noted that this procedure developed in the shadows of and in tandem with the complex BiV repair program. Hence, it might not be prudent to attempt this technique in one off instances. It is also important to stress the need for support from the intensive care service for these patients with complex physiology. In addition, every effort must be made at the time of the Super Glenn operation to optimize the inflow and outflow into the left ventricle.

The Super Glenn strategy might be countered by the argument that these patients will have minimal mortality had they embarked on the conventional single ventricle pathway with a Glenn followed by a Fontan. These numbers need to be seen in the context of survival of patients with a small left ventricle who undergo single ventricle palliation. Several studies have demonstrated that this subset has poor survival as compared to other single ventricle subsets [10, 11, 14]. This is largely driven by the fact that the right ventricle does not function optimally in the systemic position [15, 16]. A recent study by Wilson et al. [17] examining a cohort of adult HLHS survivors shows that these patients have a high prevalence of major adverse cardiovascular events over a few years of adult follow-up. For patients with unbalanced CAVC who undergo Fontan palliation, the long-term outcomes are still suboptimal. Buratto et al. [18] report a 25 year survival <60% which is improved but still suboptimal compared to other Fontan subsets. All these factors point to the fact that alternative treatment strategies might be justified. However, it needs to be acknowledged that our treatment approach does not have a follow-up long enough to demonstrate superiority/non-inferiority over the conventional Fontan pathway.

Limitations

Our study has all limitations inherent to a retrospective observational study. Though all patients were operated in one institute, they were operated by different surgeons over several years. The decision to undertake this procedure was based on expert judgement in the absence of definite criteria. Due to the low number of death/transplant events, we were unable to identify predictors for these adverse events. Patients with varied diagnoses were analysed together and small numbers did not allow us to tease out the relevance of varied diagnoses in this surgical strategy. This study does not take into account the impact of pre-Super Glenn morbidity or mortality in the evaluation of this treatment pathway.

CONCLUSIONS

The Super Glenn procedure achieves consistent growth of the left ventricle. This may be a useful strategy to help achieve a successful BiV circulation in patients with borderline left ventricle. Optimization of pulmonary blood flow is critical and pulmonary over circulation should be avoided. More studies are needed to evaluate the utility of this technique and to further define adequacy and definitions of LV growth as a means to achieving BiV circulation. This treatment approach does not have a follow-up long enough to demonstrate superiority/non-inferiority over the conventional Fontan pathway.

Presented at the 34th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Barcelona, Spain, 8–10 October 2020.

ACKNOWLEDGEMENTS

Illustration credited to Kai-Ou Tang.

Conflict of interest: none declared.

Author contributions

Supreet P Marathe: Data curation; Formal analysis; Investigation; Resources; Validation; Writing – original draft; Writing – review & editing. Breanna Piekarski: Data curation; Formal analysis; Project administration; Resources; Software. Rebecca S Beroukhim: Conceptualization; Methodology; Supervision; Validation; Writing – review & editing. Kimberlee Gauvreau: Formal analysis; Investigation; Methodology; Writing – original draft; Writing – review & editing. Christopher W Baird: Conceptualization; Validation; Writing – review & editing. Sitaram M Emani: Conceptualization; Investigation; Writing – review & editing. Pedro J del Nido: Conceptualization; Methodology; Project administration; Resources; Supervision; Validation; Writing – review & editing. Aditya K Kaza: (Conceptualization; Formal analysis; Investigation; Methodology; Project administration; Resources; Supervision; Validation; Writing – original draft; Writing –review & editing.

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Hannah Rosemary Bellsham-Revell and the other, anonymous reviewer(s) for their contribution to the peer review process of this article.

REFERENCES

ABBREVIATIONS

 
• BiV

  Biventricular

 
• BT

  Blalock–Taussig

 
• CI

  Confidence interval

 
• CMRI

  Cardiac magnetic resonance imaging

 
• IQR

  Interquartile range

 
• EFE

  Endocardial fibroelastosis

 
• HLHS

  Hypoplastic left heart syndrome

 
• LV

  Left ventricle

 
• LVEDV

  Left ventricular end-diastolic volume

 
• LPA

  Left pulmonary artery

 
• PA

  Pulmonary artery

 
• RPA

  Right pulmonary artery

 
• RVEDV

  Right ventricular end-diastolic volume