Abstract
Objectives
A minority of patients with hypoplastic left heart syndrome (HLHS) are at extremely high risk for staged palliation and can be bridged-to-heart transplantation with bilateral pulmonary artery bands, ductal stenting, and single ventricle-ventricular assist device insertion (HYBRID + sVAD). The purpose of this analysis is to assess our learning curve associated with our first ten patients with functionally univentricular ductal-dependent systemic circulation who were supported with primary HYBRID + sVAD as bridge-to-heart transplantation.
Methods
Patients were temporally separated into two cohorts: the first five and second five. Demographic, perioperative, and outcome data were collected. Continuous variables are described as median [IQR](range). Categorical variables are described as N (%). P values were calculated using Fisher exact t test for categorical variables and unpaired t tests for continuous variables.
Results
Ten patients underwent HYBRID + sVAD operations for HLHS (2017-2022). Patients in the initial cohort and the most recent cohort were similar in age and weight. Liver dysfunction and renal dysfunction were more common in the first five patients (2/5 = 40%) versus the next five patients (0/5 = 0%). Length of sVAD support was longer in the most recent five patients (98 days [64-138] vs 154 days [134-225], P = .08); however, no increase in sVAD-associated stroke or bleeding was seen in the most recent five patients. Despite very similar demographic and preoperative profiles, only two of the first five patients (2/5 = 40%) survived to heart transplantation, while all of the next 5 (5/5 = 100%) were successfully bridged-to-cardiac transplantation with HYBRID + sVAD and are alive today.
Conclusions
Our experience with primary HYBRID + sVAD as bridge-to-heart transplantation in neonates with HLHS demonstrates an important learning curve associated with this operation and approach.
Keywords
Introduction
Learning curves are a widely expected and understood part of medical training and advancement, especially in surgical specialties.1–5 The thought process, both in individuals and in the field at large, is that new skills and operative techniques must be performed multiple times and in different settings to gain an understanding of proper patient selection and management to optimize outcomes. This phenomenon is especially present in the field of congenital heart surgery, where the advent of new operations6–8 often precedes further innovation and optimization of the surgical technique and overall patient outcomes. This process of reciprocal development and refining of operative techniques is vital to further growth of the field and improved patient care.
The 2021 International Paediatric and Congenital Cardiac Code and the Eleventh Revision of the International Classification of Diseases provide the following definition for hypoplastic left heart syndrome (HLHS): “Hypoplastic left heart syndrome (HLHS) is defined as a spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch.”9,10 At the University of Florida, neonates with HLHS and other forms of functionally univentricular ductal-dependent systemic circulation are stratified into three pathways of management11,12:
Pathway 1: Standard risk patients undergo an initial Norwood Stage 1 operation. Pathway 2: High-risk neonates with noncardiac risk factors undergo an initial Hybrid Stage 1 with bilateral pulmonary artery banding and ductal stenting, and Pathway 3: High-risk neonates with important cardiac risk factors undergo an initial Hybrid Stage 1 + single ventricle-ventricular assist device [sVAD] insertion (HYBRID + sVAD).
Our comprehensive approach that stratifies neonates with HLHS and related malformations into the above three pathways is designed to maximize survival and optimize the utilization of precious donor hearts.
The HYBRID + sVAD approach consists of application of bilateral pulmonary artery bands, stent placement in the patent's arterial duct, atrial septectomy if necessary, and Berlin Heart sVAD insertion (the Berlin EXCOR pulsatile paracorporeal ventricular assist device [Berlin Heart, Inc.]), and is utilized in neonates with HLHS and other forms of functionally univentricular ductal-dependent systemic circulation with major cardiac risk factors such as large coronary sinusoids or fistulas with ventricular-dependent coronary circulation, severe tricuspid regurgitation, or severe ventricular dysfunction. This HYBRID + sVAD approach was developed at the University of Florida. The purpose of this analysis is to examine our learning curve associated with our first ten patients who were supported with primary HYBRID + sVAD as bridge-to-heart transplantation by comparing outcomes with the first five patients with the most recent five patients.
Methods
Patients
A retrospective chart review was performed of all patients who underwent VAD insertion from 2006 to 2023 at the University of Florida. Patients with HLHS and other forms of functionally univentricular ductal-dependent systemic circulation who underwent primary HYBRID + sVAD as a bridge-to-heart transplantation were included in this study. Patients who underwent VAD insertion due to other indications or did not undergo hybrid procedures were excluded. Our final cohort included ten patients with functionally univentricular ductal-dependent systemic circulation who underwent HYBDRD + VAD as bridge-to-heart transplantation. Demographic and perioperative data were collected. Table 1 documents details about the ten individual patients included in this article presented in chronological order, including diagnostic characteristics, cardiac risk factors, and outcomes.
Details About the Ten Individual Patients Included in this Article Presented in Chronological Order, Including Diagnostic Characteristics, Cardiac Risk Factors, and Outcomes.a
Abbreviatrions: AA, aortic atresia; AS, aortic stenosis; ECMO, extracorporeal membrane oxygenation; HLHS, hypoplastic left heart syndrome; MA, mitral atresia; MODS, multiple organ dysfunction syndrome; MS, mitral stenosis; NV, not intubated at time of entering the operating room for HYBRID + VAD procedure; SMA, superior mesenteric artery; V, intubated at time of entering the operating room for HYBRID + VAD procedure; VAD, ventricular assist device; VSD, ventricular septal defect.
The yellow cells provide data about the three patients in this series who have died.
Single Ventricle-VAD Protocols
The ten patients supported with sVAD in this analysis were supported with the Berlin Heart sVAD. Figure 1 shows the University of Florida HYBRID + sVAD configuration, with application of bilateral pulmonary artery bands, stent placement in the patent ductus arteriosus (PDA), and atrial septectomy if needed, along with Berlin Heart sVAD insertion. Our surgical techniques for HYBRID + sVAD insertion have been published.13,14 At the University of Florida, our approach for HYBRID + sVAD is to perform the following procedures during one single operation: application of bilateral pulmonary artery bands, atrial septectomy if needed, and Berlin Heart sVAD insertion, along with stent placement in the PDA. Although high-risk neonates with functionally univentricular ductal-dependent systemic circulation can technically undergo placement of bilateral pulmonary artery bands and sVAD insertion with maintenance of ductal patency with prostaglandin, we have not used this approach at the University of Florida. We prefer to place a ductal stent in these patients at the time of the operation for placement of bilateral pulmonary artery bands and sVAD insertion because this approach allows separation of the patient from prostaglandin infusion. In fact, all ten patients in this current series underwent placement of bilateral pulmonary artery bands and sVAD insertion with placement of the ductal stent during the same operation. Technical details of this operative strategy have been published.13,14
The University of Florida HYBRID + sVAD configuration, with application of bilateral pulmonary artery bands, stent placement in the patent ductus arteriosus (PDA), and atrial septectomy if needed, along with Berlin Heart sVAD insertion. Abbreviations: HLHS, hypoplastic left heart syndrome; PA, pulmonary artery; sVAD, single ventricle-ventricular assist device.
Our detailed protocols for sVAD management and anticoagulation have also been published.13,14 Briefly, sVAD settings are titrated to achieve an initial cardiac index of 4 L/min/m2. Neonatal sVAD target hemodynamic parameters are similar to the target hemodynamics after any other Norwood (Stage 1) operation or Hybrid (Stage 1) operation. After insertion, the sVAD rate is gradually increased as needed to ensure adequate cardiac output and systemic tissue perfusion. The patient is extubated as soon as possible. With adequate cardiac output provided by the sVAD, end-organ function is optimized. While supported with the sVAD, ongoing nutritional and physical rehabilitation maximize the functional status of the patient.
In patients with functionally univentricular ductal-dependent systemic circulation who undergo HYBRID + sVAD, no anticoagulation is given during the first 24 h after sVAD insertion. The following anticoagulation protocol is then initiated:
Bivalirudin: Bivalirudin is initiated on postoperative day 1. During hours 24 to 72, bivalirudin is titrated to a partial thromboplastin time of 50 to 70 s. After 72 h, bivalirudin is titrated to a partial thromboplastin time of 70 to 100 s. Aspirin: Aspirin is started on day 5 after sVAD implantation at a dosage of 5 mg/kg/d (divided into two daily doses), and aspirin is increased each week until a dosage of 30 mg/ kg/d is reached by week 4. Dipyridamole: Dipyridamole is started on week 5 after sVAD implantation at a dosage of 2.5 mg/kg/d, and dipyridamole is increased twice each week until a dosage of 15 mg/kg/d is reached by week 6. Omega-3 fatty acid: Omega-3 fatty acid is typically started at three to four months after sVAD implantation.
Statistics, Database, and Institutional Review Board
Two cohorts were created by dividing our experience into the first five patients and the most recent five patients, in order to compare preoperative patient profiles and postoperative outcomes. Statistical analysis included univariable descriptive statistics. Continuous variables are described as median (interquartile range = IQR = Q1–Q3, range = minimum–maximum), while categorical variables are described as N (%). P values comparing the two cohorts were calculated using Fisher exact t test for categorical variables and unpaired t tests for continuous variables. All statistical examinations were conducted utilizing Microsoft Excel 2021.
Data were sourced from a registry and database (CardioAccess Incorporated, and Fort Lauderdale: http://www.cardioaccess.com) that uses software certified by The Society of Thoracic Surgeons Congenital Heart Surgery Database and has been prospectively maintained on all patients undergoing pediatric and/or congenital cardiac surgery at the University of Florida. This study was approved by the University of Florida Institutional Review Board with waiver of the need for consent: IRB202102664.
Results
Study Population and Outcomes: Entire Cohort
Demographic, perioperative, and outcome data for the entire cohort are summarized in Table 2. Ten patients underwent HYBRID + sVAD palliation from 2017 to 2022 (median age at sVAD implantation was 21.5 days [19.25-28.75], median weight at sVAD implantation was 3.21 kg [3.01-3.79]. One patient in the cohort was supported with extracorporeal membrane oxygenation (ECMO) prior to sVAD insertion. Prior to sVAD insertion, liver dysfunction was present in 2/10 (20%) patients, and renal dysfunction was present in 2/10 (20%) patients. Median support time was 136 days [98.75-160]. While on VAD support, stroke occurred in 4/10 (40%) patients, and bleeding occurred in 1/10 (10%) patients. In the whole cohort, 7/10 (70%) patients survived to transplant and are alive at the time of this writing (June 15, 2025).
Characteristics of HYBRID + sVAD Patients.
Abbreviation: ECMO, extracorporeal membrane oxygenation; sVAD, single ventricle-ventricular assist device.
At the University of Florida, during the period of this analysis (2017-2022), no neonates with HLHS were managed with compassionate care or died in the period between admission and the first intervention. In 2024, one neonate with HLHS was managed with nonoperative compassionate care secondary to a genetic syndrome associated with multiple important noncardiac congenital anatomic abnormalities. 11
Study Population and Outcomes: Divided Cohorts
The overall cohort was split into two even cohorts of five patients by dividing the ten patients into the first five patients and most recent five patients. Demographic, perioperative, and outcome data are summarized in Table 2, stratified by cohort. Age at sVAD insertion was similar between cohorts (median age at sVAD implantation in the first five patients was 21.5 days [19.25-28.75] vs 23 days [19-25] days in the next five patients, P = .37). Weight at sVAD insertion was also similar between cohorts (median weight at sVAD implantation in the first five patients was 3.25 kg [2.9-3.85] vs 3.16 kg [3.07-3.6] in the next five patients, P = .80). None of the first five patients in this series were supported with ECMO prior to HYBRID + sVAD support, while one out of the next five patients (20%) was supported with ECMO support prior to HYBRID + sVAD support. Of note, liver dysfunction and renal dysfunction were present in two of the five patients (40%), but not in any of the next five patients (P = .44). Length of sVAD support was longer in the most recent five patients (98 days [64-138] vs 154 days [134-225], P = .08). Stroke on sVAD occurred at equal rates in both cohorts, with 2/5 (40%) patients in each group experiencing stroke. Bleeding only occurred in one of the first five patients (20%) and did not occur in any of the next five patients. Survival to transplant occurred in two out of the first five patients (2/5 = 40%), but all five of the next five patients (5/5 = 100%) survived to heart transplantation (P = .17). Figure 2 shows the learning curve at the University of Florida with the HYBRID + sVAD approach. Despite very similar demographic and preoperative profiles across eras, only two of the first five patients (2/5 = 40%) survived to heart transplantation, while all of the next five (5/5 = 100%) were successfully bridged-to-heart transplantation with HYBRID + sVAD and are alive today.
The learning curve at the University of Florida with the HYBRID + sVAD approach. Despite very similar demographic and preoperative profiles across eras, only two of the first five patients (2/5 = 40%) survived to heart transplantation, while all of the next 5 (5/5 = 100%) were successfully bridged-to-heart transplantation with HYBRID + sVAD and are alive today. sVAD, single ventricle-ventricular assist device.
Discussion
Staged palliation with an initial Norwood (Stage 1) operation is an excellent option for most patients with HLHS, with some centers reporting survival above 90% at one year of age. 11 However, a subset of patients with HLHS are high risk for conventional staged palliation and experience far worse outcomes following traditional staged palliation in comparison with their standard risk counterparts, with one-year survival of approximately 50% or less. 15 It is a fact that some patients with HLHS and related malformations are exceedingly high risk for Norwood or hybrid palliation. While the definition of high risk varies by institution, this high-risk cohort includes neonates with major cardiac risk factors such as large coronary sinusoids or fistulas with ventricular-dependent coronary circulation, severe tricuspid regurgitation, severe ventricular dysfunction, or intractable arrhythmias. Primary cardiac transplantation offers the best option for survival of these challenging neonates; however, waitlist mortality must be minimized. 11 Given long wait times for neonates, strategies must be developed to bridge these patients to cardiac transplantation safely. In order to address this challenge, we developed our HYBRID + sVAD approach at the University of Florida. Others have now also begun to utilize this approach. 16
Because others have now adapted our HYBRID + sVAD approach for high-risk patients with HLHS, we thought it would be useful to examine our learning curve with this approach so that others may benefit from the evolution of our experience. In our analysis, our cohort of ten patients was temporally split into the first half versus the second half, in order to examine our learning curve and determine any changes in patient selection, management strategies, and outcomes in more recent patients who underwent the HYBRID + sVAD palliation. Despite very similar demographic and preoperative profiles in our first five patients in comparison with our last five patients, only two of the first five patients (2/5 = 40%) survived to cardiac transplantation, while all of the next five patients (5/5 = 100%) have been successfully bridged to cardiac transplantation with HYBRID + sVAD and are alive today. Our experience with primary HYBRID + sVAD as bridge to cardiac transplantation in neonates with HLHS demonstrates an important learning curve associated with this operation and approach.
Patients in the initial cohort and the most recent cohort were similar in age and weight. Liver dysfunction and renal dysfunction were far more common in the first five patients (40%) as opposed to the next five patients (0%). The duration of sVAD support was longer in the most recent five patients (154 days [134-225]) compared with the previous five patients (98 days [64-138]), although this difference was not statistically significant (P = .08). This difference in support times between the two cohorts was likely clinically significant although this difference was not statistically significant. Importantly, these longer support times were not associated with an increased incidence of sVAD-associated stroke or bleeding in these most recent five patients. The findings of increased survival in the most recent cohort as well as the absence of an increase in sVAD-associated stroke or bleeding despite longer support times in the most recent five patients represent promising trends and possibly are a result of our growing experience in both the operating room and intensive care unit with this subset of extremely high-risk patients.
Although the reasons for the improvement in our outcomes over time are clearly multidisciplinary and multifactorial, the following critical elements of our evolution are all likely contributory:
An evolving multidisciplinary approach is used to manage these complex patients. All neonates with functionally univentricular ductal-dependent systemic circulation and any of the following high-risk features are felt to be extremely high risk for staged palliation and are therefore discussed early in their life in a multidisciplinary setting to consider possible bridge-to-heart transplantation with HYBRID + sVAD stabilization:
✓ large coronary sinusoids or fistulas with ventricular-dependent coronary circulation, ✓ severe systemic atrioventricular valvar regurgitation, and/or ✓ severe ventricular dysfunction. Preoperative changes include the rapid initiation of mechanical circulatory support, prior to the development of noncardiac end-organ dysfunction such as renal dysfunction or hepatic dysfunction. If the patient is not initially suitable for sVAD cannulation and support, ECMO is utilized as a bridge to sVAD. Our strategy is based upon the goal of initiation of sVAD support prior to the development of irreversible renal dysfunction or hepatic dysfunction. Intraoperative changes include the continuous evolution of collaboration between the surgical team and the interventional cardiology team based on ongoing experience, as exemplified by the surgical placement of a hemoclip as a radiographic marker at the junction of the left pulmonary artery and the arterial duct to aid subsequent positioning of the ductal stent. A detailed description of our current surgical techniques for HYBRID + sVAD insertion has been published previously.13,14 Postoperative changes include the evolution of our strategies for VAD support and VAD management, based on the following principles:
✓ The transition from primary use of heparin to primary use of bivalirudin for anticoagulation of patients supported with VAD, as well as the overall evolution of our anticoagulation protocol to the current protocol as described earlier in this article. ✓ Our anticoagulation protocol has also evolved with the gradual implementation of our current protocol of increasing the dose of aspirin and persantine (ie, dipyridamole) given to our patients supported with Berlin Heart, so that they receive the full dose of these medications within six weeks of VAD insertion. We believe that this strategy facilitates longer duration of Berlin Heart support with fewer clots. ✓ The use of an initial sVAD cardiac index of 4 L/min/m2 to ensure adequate cardiac output and systemic tissue perfusion in neonates with parallel systemic and pulmonary circulations. Neonatal sVAD target hemodynamic parameters are similar to the target hemodynamics after any other Norwood (Stage 1) operation or Hybrid (Stage 1) operation. After insertion, the sVAD rate is gradually increased as needed to ensure adequate cardiac output and systemic tissue perfusion. ✓ Extubation and mobilization of the patient supported with sVAD as soon as possible. ✓ Ongoing nutritional and physical rehabilitation of the patient supported with the sVAD to maximize the functional status of the patient. ✓ Our protocol of nutritional rehabilitation of our patients supported with Berlin Heart often utilizes a combination of elemental enteral formula and only the intralipids component of the total parenteral nutrition (TPN) during the first six to eight weeks after VAD insertion, to facilitate growth and maintenance of an anabolic state.
The rationale for this approach is to maximize survival and optimize the utilization of precious donor hearts.
The elements described in detail above represent lessons that we have learned as we navigated our learning curve associated with combined hybrid procedure and sVAD insertion in high-risk neonates with HLHS. These lessons represent actionable strategies for the reader to consider as they contemplate utilization of combined hybrid procedure and sVAD insertion in high-risk neonates with HLHS.
Value of this Analysis
The HYBRID + SVAD approach was developed at the University of Florida to allow the high-risk neonate with HLHS who is not a suitable candidate for staged palliation to be safely bridged to cardiac transplantation. This approach is now being utilized at multiple institutions across the world. Our experience demonstrates an important learning curve associated with this approach. This article adds to the extant literature by examining our learning curve with this novel approach and sharing the lessons that we have learned with other centers who may utilize this approach in the future.
Limitations
Our study possesses several limitations. With only ten patients in the overall cohort, and further splitting the series into two cohorts of five patients, this study lacks the sample size to make generalizable conclusions about these patients and their outcomes. While we can highlight trends in patient selection and a marked improvement in outcomes following our center gaining experience managing these patients, we cannot say if these findings are generalizable. Additionally, with only three deaths in the cohort, we do not have the statistical power for formal delineation of factors associated with mortality in this complex subset of patients. Finally, all of the statistical comparisons reported in this paper are limited by the small sample size of each of the two cohorts (n = 5).
Conclusions
Our center's experience with HYBRID + sVAD as bridge to heart transplantation for patients with HLHS who are at high risk for conventional Norwood palliation demonstrates an improvement in patient outcomes in more recent patients, likely secondary to increased experience managing these patients at our center. Future studies should aim to determine what variables contribute to successful or unsuccessful outcomes, and these studies can help further optimize patient selection for this unique and evolving procedure. Despite very similar demographic and preoperative profiles in the early cohort versus the most recent cohort, only two of the first five patients (2/5 = 40%) survived to transplant, while all of the next 5 (5/5 = 100%) were successfully bridged-to-heart transplantation with HYBRID + sVAD and are alive today. Our experience with primary HYBRID + sVAD as bridge-to-cardiac transplantation in high-risk neonates with HLHS and related forms of functionally univentricular ductal-dependent systemic circulation HLHS demonstrates an important learning curve associated with this operation and approach.
Footnotes
Abbreviations
Authors’ Note
IRB Approval: This study was approved by the Institutional Review Board at the University of Florida and qualified as Exempt: IRB202102664.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
